Here Is a Range of New Agents, Molecular Markers Ethics and Human Rights

European Urology Today First Edition EUT Congress News 32nd33rd AnnualAnnual CongressCongress ofof thethe EuropeanEuropean AssociationAssociation ofof UrologyUrology Saturday, 2517 MarchMarch 20182017 Copenhagen,London, 24-2816-20 March 20182017

Meeting the challenges in urogenital diseases EU Health Commissioner Andriukaitis urges stronger collaboration

By Joel Vega and Erika de Groot currently numbers 29 active units in 11 EU member Dr. Deepansh Dalela (US) received the Hans EAU Ernest Desnos Prize for his contributions to states. Marberger Award for the best European paper urological history, while Hashim Ahmed (GB) To the rhythmic, high energy beat of the published on minimally invasive surgery in was awarded the EAU Prostate Cancer Research synchronized, four-man Copenhagen Drummers Chapple also highlighted the crucial role of the EU in urology. Prof. Sergio Musitelli (IT) received the first Award. band, the 33rd Annual EAU Congress opened creating the ERNs which he said will lead to better data yesterday with European Commissioner for Health collection and mutual collaboration among European and Food Safety, Prof. Vytenis Andriukaitis (LT) scientists and clinical professionals. “To ensure the urging the audience to collaborate in the European sustainability of this project we need to form Reference Networks (ERNs). partnerships and work on common goals,” he said.

“This flagship project reflects not only the need The Opening Ceremony traditionally highlights the to further strengthen our collaboration, but also EAU’s honorary members and awardees. Chapple the fact that we can and have achieved a lot if we conferred the title of Honorary Members to Gunnar put together our resources, knowledge and Aus (SE), Patrick Coloby (FR), Mani Menon (US) and commitment,” said Andriukaitis. He emphasized Ajit Vaze (IN). Prof. Vicenzo Mirone (IT) received the that the synergies of expert centres are invaluable EAU Willy Gregoir Medal 2018. Prof. Didier Jacqmin and will come a long way in providing better (FR) was awarded the EAU Frans Debruyne Lifetime healthcare, particularly to those with rare Achievement Award, while Prof. Selcuk Silay (TR) diseases. won the EAU Crystal Matula Award.

Andriukaitis thanked EAU Secretary General Prof. “For urologists our biggest concern is how to boost Chris Chapple for his personal efforts and our medical and surgical strategies, and balance commitment to ERNs with the involvement of these without neglecting our core competencies,” urological expertise in the eUROGEN network which said Mirone. Commissioner V. Andriukaitis: “Synergies across Europe are invaluable.”

New agents and imaging African and European views to improve PCa therapies on HIV and circumcision Experts’ forecasts at ESO Prostate Cancer Observatory By Erika de Groot Additional benefits include lower incidence of urinary tract infection in infants, penile hygiene, and There is a range of new agents, molecular markers Ethics and human rights. Medical safety concerns. prevention of balanitis and posthitis. The risk of and improved imaging techniques that over the These are factors that differentiate African and penile cancer is also lowered. Mangwiro said that MC coming years will help doctors to further optimise European views on the role of circumcision in HIV is “not a silver bullet.” It has a 60% efficacy and their management of prostate cancer patients, prevention as discussed today in the Joint Session of should be used as part of a comprehensive HIV particularly those with advanced or high-risk disease. the European Association of Urology (EAU) and the programme. Pan-African Urological Surgeons Association (PAUSA) During the 5th European School of Oncology (ESO) chaired by Dr. Allen Chiura (ZW) and Prof. Dr. Rien According to Mangwiro, the VMMC (voluntary medical Prostate Cancer Observatory held yesterday, a panel Nijman (NL). male circumcision) programme has done well; it has of prostate cancer (PCa) specialists presented their achieved its scale up targets and is currently expectations for promising medical approaches that In his lecture Successes and Challenges of Male developing a new strategy that will introduce a aim to boost the current management of PCa. Full audience at the 5th ESO Prostate Cancer Observatory Circumcision in the HIV era, Dr. Tonderayi Mangwiro sustainability component. (ZW) stated that male circumcision (MC) averts a The multidisciplinary presentations covered new greater incidence of ulcerative sexually-transmitted Dr. Nicolai Lohse (DK) listed varying recommendations developments and forecasts for research, surgery, Prof. Steven Joniau (BE), who co-chaired the session infections (STIs) and the susceptibility of the foreskin for neonatal MC in Europe, Canada and the United active surveillance, imaging, pathology, and medical with Prof. Riccardo Valdagni (IT), said: “For me, the to abrasions during intercourse. States. oncology. The perspective and concerns of patient session showed that we need to better understand groups were also discussed by Prof. Louis Denis (BE) the disease with the aid of the many tools we have as a representive for these groups. now such as PSMA, MRI and others, in combination with the standard tests such as PSA. Tools such as “My expectations for 2018 and next year are further PSA still have their use despite the entrance of new results from STAMPEDE and the potential changes in methods. It is important to avoid over-treatment and the standard of care for metastatic hormone-naïve instead focus on the detection and treatment of prostate cancer (mHNPC) patients,” said medical high-risk cancers.” oncologist Dr. Ananya Choudhury (GB) who gave the view from her discipline. Joniau reiterated Touijer’s key message as he stressed the importance of AS to avoid over-treatment of Choudhury added that results are awaited from low-risk PCa. sequencing and combination studies. She mentioned hormonal agents being tested in trials such as Dr. Ivo Schoots (NL) discussed prostate MRI and its SPARTAN (Apalutamide), PROSPER (Enzalutamide), diagnostic accuracy, noting that a limitation of MRI is STAMPEDE/LATITUDE (abiraterone) as well as disagreement among radiologists. “There are now STAMPEDE, which is testing the combination of proposed adjustments to the PIRADS text,” said abiraterone and enzalutamide. Schoots. “Looking back, to 2017, prostate MRI shows maturation with its strength and limitations.” Giving the urological perspective on active surveillance (AS), Prof. Karim Touijer (US) stressed its importance Prof. Rodolfo Montironi (IT) discussed developments and noted that its increasing use necessitates in pathology such as the update of PCa grading, educating the physician in order to provide better intraductal carcinoma of the prostate, the routine counselling to patients. Touijer stated that it is molecular markers used by pathologists with multiple important is to collect more information on AS and to clinical purposes, and the potential of liquid biopsies reassure the patient about future treatment options. such as urine and blood.

Saturday, 17 March 2018 EUT Congress News 1 Today’s Industry History Office Special Session Sessions & Workshop Exploring history of urology in Denmark, Scandinavia and beyond

Industry sessions and workshop, By Loek Keizer Initially, the Association had a fixed quota of all starting at 18:00 hrs members from each country, although over time this The interconnectedness of urology in Europe is arrangement was replaced by automatic membership exemplified by the collaboration evident in the when a urologist joined their respective national Multi-disciplinary team (MDT) perspectives for Scandinavian countries and the Scandinavian society. Iceland joined the Association in 1976. early, optimised treatment of mCRPC Association of Urology in particular. ASTELLAS PHARMA EUROPE LTD. Since 1995, the official language of the Association Green Area, Room 1 (Level 0) On the first day of EAU18, the 33rd Annual EAU has been “bad English” (as opposed to “bad Congress, held this year in Copenhagen, the EAU Swedish” – the words of Prof. Jens Andersen (DK)). History Office welcomed prominent Danish and The decision to switch to English was made in order Optimising patient management in urogenital Scandinavian speakers to give the audience a flavour to be more inclusive to the Finnish delegates and also cancers of the long history of regional cooperation, as well as to attract greater international interest. Prof. IPSEN PHARMA some biographies of eminent Danish urological Andersen recollected that board of the Scandinavian Green Area, Room 2 (Level 0) pioneers. Prof. Beisland, speaking about the history of the Scandinavian Association had a lot of discussion at the time, amid Association of Urology. fears of a loss of national identity. Later in the Specialty Session, EAU History Office Looking beyond mLUTS to BPE and BOO: Chairman Prof. Philip Van Kerrebroeck (NL) gave surgical societies in the world. It was a relatively slow Holm and Hald Does it really matter? some background information on the new EAU Ernest process of separating urology from general surgery, Drs. Jorgen Kvist Kristensen (DK) and Jørgen Nordling RECORDATI SPA Desnos Prize, Dr. Johan Mattelaer (BE) gave a preview with the first national societies being established in (DK) presented biographies of Profs. Hans Henrik Red Area, Room 1 (Level 0) of his latest book, and Mr. Jonathan Goddard (GB) the 1950s and 1960s.” Holm and Tage Hald (DK) respectively, two incredibly looked at the role of British urologists in the First influential and respected urologists. Holm was a Combating UTI – Shifts of paradigm World War, with 2018 marking the centenary of the In 1950, the Scandinavian Association of Urology laid pioneer in interventional ultrasound, combining BIONORICA end of the war. its foundations as an informal group, a ‘travelling ultrasound with biopsies, treatment of cysts and Blue Area, Room 5 (Level 0) club’ for urologists in Denmark, joined later by percutaneous nephrostomy in the 1960s. Establishing a Nordic Society urologists from Norway, Sweden and Finland. In Prof. Christian Beisland (NO) spoke about the 1956, a proposal was made to formalise this Tage Hald, the 1999 Willy Gregoir Award Winner, Workshop extensive history of urology in the Scandinavian arrangement in a proper Association, albeit with was a founding member of the International countries as well as the establishment of an some initial scepticism by representatives from Continence Society, and was tasked with Bladder EpiCheck – Breaking the glass ceiling international urological association for the region. Norway and Sweden. Beisland: “In the end, the establishing uniform terminology in that field. “He of urine markers in NMIBC monitoring Association was famously founded in the sauna of was a much-admired tutor and he supervised a NUCLEIX Beisland said: “The Nordic Surgical Society (NKF) was Professor Tuovinen’s summer house in Ojakkala, huge range of topics as Professor at Herlev Green Area, Room 10 (Level 1) first founded in 1893, making it one of the oldest Finland.” Hospital,” Nordling concluded.

Robotics not a priority in developing world Joint EAU-SIU session tackles controversial issues in urology European Urology Today

Editor-in-Chief By Joel Vega “It has nothing to do with the surgery,” said Dasgupta, Prof. M. Wirth, Dresden (DE) adding“a fool with a tool is still a fool.” Costly robot-assisted surgery is not viable in the Section Editors developing world considering that there is no Conversely, Rawal anchored his arguments within the Prof. T. E. Bjerklund Johansen, Oslo (NO) context of the Indian experience where he said there is Mr. Ph. Cornford, Liverpool (GB) convincing data on the superiority of these expensive a clear need for a more efficient alternative to open Prof. O. Hakenberg, Rostock (DE) robot technologies, says a UK-based expert. Prof. P. Meria, Paris (FR) and laparoscopic approaches. He noted that there are Dr. G. Ploussard, Paris (FR) During the joint EAU- Société Internationale d’Urologie opportunities to save money with robotic surgeries, P. Dasgupta stresses a point during his lecture on the role of Prof. J. Rassweiler, Heilbronn (DE) (SIU) session, part of the Urology Beyond Europe and mentioned that robotic procedures in India are robotic surgery in developing countries. Prof. O. Reich, Munich (DE) programme, experts clashed on the perceived much less expensive when compared, for instance, Dr. F. Sanguedolce, London (GB) importance of robot-assisted surgeries particularly in with the United States. He also insisted that there are involvement have distant metastases anyway,” he Dr. Z. Zotter, Budapest (HU) prostate disease. clear benefits in terms of blood loss, warm ischemia said. time, and a shorter learning curve for surgeons Founding Editor “Strive to become a better surgeon, particularly if you compared to laparoscopy. Witjes opposed Egawa on urothelial cancer, arguing Prof. F. Debruyne, Nijmegen (NL) are in the developing world. Stop obsessing about that metastasectomy is of limited use. “There is almost Editing and Coordination technology… There are no differences in outcomes,” The session also covered some other key controversies no role for surgery in metastatic UC, but in selected J. Vega said Prof. Prokar Dasgupta (GB). “Only 5% of in uro-oncology. Prof. Axel Bex (NL) argued that cases removal of initial or recurrent metastatic disease operations are robotic. The cost of robot-assisted lymphadenectomy in renal cancer is unnecessary, can increase cancer specific survival (CSS).” Onsite Reporting and Editing procedures rose by 13% in three years, resulting in against the pro-statements of Dr. Frederic Pouliot (CA), E. de Groot around $2.5 billion in additional healthcare costs. The whilst Profs. Shin Egawa (JP) and Fred Witjes (NL) The session also took up other issues in general L. Keizer robot is an unnecessary luxury in the developing debated the merits of metastasectomy in urothelial urology such as social media in clinical medicine. J. Tidman world.” cancer and Profs. Peter Wiklund ( SE) and Paolo J. Vega Gontero (IT) discussed the necessity of intracorporeal Prof. Declan Murphy (AU) argued against Prof. Jim X. Zheng Dasgupta rebutted the arguments of Dr. Sudhir Rawal diversion. Catto (GB) with the latter warning of the potential Communications and Promotion (IN) noting that a centre needs to perform over 100 disadvantages of frequent social media use, such as J. Bloemberg cases of robot-assisted surgery in order for it to be Bex said the likelihood of lymph node involvement is loss of confidentiality, the limited understanding of M. van Gurp cost-effective. He also examined the issue of a shorter small and the low overall rate of local recurrence does complex issues that cannot be properly examined on I. Moerkerken hospital stay, stating that hospital stay depends on the not seem to be altered by lymphadenectomy. social media platforms, and the loss of a doctor’s country where the patient lives. “Between 58 to 95% of patients with lymph node professional boundaries. Advertising R. A. Matser L. Schreuder Lay-Out/Printing D. Blom G. Smit Biomarkers: A new pillar in diagnosis of BCa? EUT Editorial Office PO Box 30016 Major shift in EAU Guidelines anticipated 6803 AA Arnhem The Netherlands T +31 (0)26 389 0680 Prof. Arnulf Stenzl (DE), Scientific Congress Office need to find more data, and we are getting closer. Debate “winners” [email protected] Chairman looked back on a well-attended Specialty You could almost say that it’s done. Several Experts like Profs. David McConkey (USA), Joan Session on bladder cancer on Friday, the first day of speakers and audience members are already using Palou (ES), Maurizio Brausi (IT) and Jim Catto Disclaimer EAU18. The session consisted of a series of case- molecular markers, despite not being in the (GB) presented cases and led discussions on No part of European Urology Today (EUT) may be based debates between some of the biggest names in guidelines.” topics like cystoscopy, treatment options reproduced without written permission from the uro-oncology. following molecular classification and what to do Communication Office of the European Association of Urology (EAU). The comments of the reviewers are their Despite not being part of the EAU Guidelines when BCG fails. own and not necessarily endorsed by the EAU or the The wide variety of debates had a common theme: recommendations yet, Prof. Stenzl anticipates a Editorial Board. The EAU does not accept liability for the consequences of inaccurate statements or data. Despite biomarkers are maturing as a third pillar in diagnosis. “major shift” in the coming years. “This is a “It’s hard to say that there were winners in these of utmost care the EAU and their Communication Office Stenzl: “We don’t want to rely just on the pathologist, pressing issue, there’s a lot of uncertainty at the ‘debates’,” Prof. Stenzl conceded. “This topic is Colophon cannot accept responsibility for errors or omissions. so we’ve used clinical assessment as well. And now moment. We know that these things will be much too sophisticated and grey to have clear the use of biomarkers is evolving into a feasible third changing, there’s not been a change for decades in “winners”. Nevertheless, this session was one of pillar.” bladder cancer Guidelines. Studies with thousands the most important and well-attended of the day. of patients are being published. There is an unmet These kinds of case-based debate sessions could “All these discussions took place in areas where need, and there is good data. I expect a change to be something we will be seeing more of at the the EAU Guidelines are not conclusive. Urologists the EAU Bladder Cancer Guidelines soon.” Annual Congress.”

2 EUT Congress News Saturday, 17 March 2018 Raising the next generation of key opinion leaders Young Academic Urologists report on recent achievements

By Jen Tidman generation of key opinion leaders, award winners “At the end of the day, the future is in your hands,” • Best paper published in 2017 by the Prostate and Association of Academic European Urologists Chapple said, “Look on the website for grants, Cancer YAU group – Dr. Roderick Van den Bergh The Young Academic Urologists (YAU) showcased the members. “The future belongs to those who believe activities, how to get involved, and help the EAU (NL) achievements of their talented and already- in the beauty of their dreams,” said Silay, quoting achieve its mission statement.” • Best poster presented at EAU 2018 by the Mens renowned members at a specialty session. Dr. Eleanor Roosevelt. He encouraged EAU members Health YAU group – Dr. Giorgio Ivan Russo (IT) Michiel Sedelaar (NL) introduced Chairman Prof. under 40, affiliated to an academic institution, and Dr. Panagiotis Kallidonis (GR) said it was difficult to • Reviewer of the year from YAU – Dr. Andrea Selçuk Silay (TR) who has not only expertly guided with at least five publications to their names, to apply report on all of the YAU non-oncology working Necchi – collected by Prof. Evangelos Liatsikos the YAU over the past two years, but is also this to join the group. groups’ achievements over the past 12 months into a (GR) on behalf of winner year’s Crystal Matula award winner. ten-minute presentation, but managed to show that Prof. Chris Chapple (GB), giving the Secretary the Functional, Men’s Health, Paediatrics, Trauma & Silay ran through the accomplishments of the group General’s perspective of the role of YAU within EAU, Reconstructive, and Endourology-Lithiasis groups all over the six years since its inception. 84% of YAU said the Executive and Board were very keen to made robust contributions to the peer-reviewed members are presenting at EAU18, 44.1% have include members in all activities, but they should be literature, academic meetings, educational courses, received a local or international scientific award, proactive in getting involved: “Things don’t just and ongoing research. “There is a lot of work being 37.7% are journal editors or associate editors, 19.4% happen, they have to be made to be happen. You are done in these groups. All of these people are going to have presentation or hands-on tutor responsibilities at the stage in your careers when you have to make develop themselves and provide something better for at ESU courses, 50.6% are involved in the EAU things happen.” our specialty.” Sections, 11.6% are involved in Guidelines panels, four members have won Matula awards, and over 80 He said members should join the Sections to build Dr. Guillaume Ploussard (FR) said that the technology PubMed papers have been published (21 in 2017). The expertise, get involved with the Research Foundation, (UroTechnology and Robotics) and oncology (Bladder, group has also contributed to EAU Section and submit to the three EAU journals, work on ESU Renal and Prostate) working groups had been Regional meetings, organised its own specific courses, and contribute to the Guidelines and Patient similarly successful in the same areas, “Last year was meetings, and at EAU18 will be running courses on Information groups. He stressed the importance of very good for these groups. I am sure 2018 will be presentation and leadership skills. networking, evidence-based rather than eminence- even better.” based medicine, and embracing the whole field in Through teamwork and a formula of “enthusiasm + order to maintain control as a urologist rather than The following YAU awards were presented by Prof. Dr. Sedelaar and Prof. Silay chairing the meeting of the Young trust + respect”, the YAU is raising the next becoming a technician. Hein Van Poppel (BE): Academic Urologists.

Award Gallery

Congress news...... 1

Congress highlights ...... 2/3

What does the urologist need to know about EDCs...... 5

Complications after open radical cystectomy . 6

Novel antibiotics in treating Urinary Tract C. Chapple awards V. Mirone with the D. Jacqmin receives the EAU Frans Debruyne S. Musitelli receives the EAU Ernest Desnos Prize from Infections...... 7 EAU Willy Gregoir Medal Life Time Achievement Award from C. Chapple C. Chapple Novel modalities for nodal staging in prostate cancer...... 8

Precision medicine in bladder cancer. . . . 9

Infectious complications and fURS. . . . .11

Ernest Desnos: Honouring urology historians.12

EAU Guidelines: Ensuring consistent European urological care...... 13

Update in vaginoplasty technique. . . . . 14 S. Silay receives the EAU Crystal Matula Award from D. Dalela accepts the EAU Hans Marberger Award from H. Ahmed accepts the EAU Prostate Cancer Research C. Chapple and M. Frazzette from LABORIE C. Chapple and E. Dourver from KARL STORZ Award from C. Chapple and F. Schröder from the Managing complex cases in functional FHS FOUNDATION urology...... 15

Residual fragments - an ongoing headache after fURS...... 16

Is TURP safe in frail elderly men or is MIT better?...... 18

My journey in prosthetic urology . . . . . 19

Oncological outcomes following robotic-assisted RC...... 20

Antibiotic treatment’s collateral effects. . . 22

C. Chapple congratulates G. Aus with his C. Chapple congratulates P. Coloby with his C. Chapple congratulates M. Menon with his Office Urology: Meeting the challenges. . . 23 EAU Honorary Membership EAU Honorary Membership EAU Honorary Membership Introducing European Urology Oncology . . 24

Predicting resistance to BCG therapy . . . 25

Robotic radical cystectomy...... 26

Best Abstracts: First prize winners. . . . 28

ESU Masterclasses: Designed and aimed to educate...... 29

Low-intensity ESWT...... 30

Prof. C. Chapple congratulates A. Vaze with his If you want to find out more about our upcoming meetings and projects, please visit the EAU Wall in the Green Area. Shared decision-making in prostate EAU Honorary Membership cancer care...... 31

Saturday, 17 March 2018 EUT Congress News 3 BAVARIAN NORDIC IS STRIVING TO BRING NOVEL TARGETED VACCINES TO MAXIMIZE IMMUNOTHERAPY IMPACT FOR CANCER PATIENTS

Our innovative oncology platform is designed to specifically target a variety of challenging tumor types. We have developed a portfolio of active cancer immunotherapies, designed to alter the disease course by eliciting a robust and broad anti-cancer immune response while maintaining a favorable risk-benefit profile.

Multiple clinical trials are ongoing in collaboration with the NCI, NIH, academia and industry partners. Through numerous industry collaborations, we seek to explore the potential synergies of combining our immunotherapies with other immune-modulators.

BAVARIAN-NORDIC.COM 4 EUT Congress News Saturday, 17 March 2018

1023433_Annonce_EUA_Jan_2018.indd 1 24/01/2018 09.46 What does the urologist need to know about EDCs? Multi-sectoral action is needed to reduce and eliminate Endocrine Disrupting Chemicals

Prof. Gert R. Dohle intra-uterine exposure to pseudo-estrogens and observed an significant increase in the incidence of wecf.org. Special attention is focused on alternatives Erasmus MC anti-androgens. Recently, it was shown that the use of testicular cancer (TC) in western countries. In the for pesticides and plastics. Rotterdam paracetamol during pregnancy doubles the risk of Netherlands, as in most other European countries, the Rotterdam (NL) cryptorchidism. Other exposures possibly involved in incidence of testicular cancer has more than doubled Key points male maldevelopments are air pollutions (diesel), in the last two decades. Although prognosis is good in 1. Testosterone is essential for normal male maternal and paternal smoking. Children born after terms of disease survival, many of these men will be development; IVF have an increased risk of hypospadias. hypogonadal after treatment. Infertility is high in 2. Testicular maldevelopment can result in these men: at time of diagnosis 50% of these men cryptorchidism, hypospadias, male infertility and In animal studies different industrial chemicals have have low sperm quality and 12% are azoospermic. testicular cancer: testicular dysgenesis syndrome been shown to cause maldevelopment of the male (TDS) is the common links between these genitalia. These chemicals have a similar structure to At Erasmus MC we have shown that the origin of diseases; estrogens and are also named pseudo-estrogens or testicular cancer occurs during fetal life. TC arises 3. Genetic abnormalities, life style factors and Endocrine disrupting chemicals (EDCs) influence our xeno-estrogens. They can easily pass the placenta and from embryonic germ cells that have failed to endocrine disrupting chemicals (EDCs) are the health, including male genital development and male act as estrogen, disrupting testicular development. mature appropriately. These precursor cells of TC main causes of TDS; reproduction. There is an increase in most western Other chemical compounds have an anti-androgenic are known as carcinoma in situ (GNCIS). Only after 4. Male infertility and congenital male societies in male reproductive disorders: the most action in the male fetus. EDCs are common in our puberty, when testosterone levels increase, TC will hypogonadism are associated with obesity, type 2 striking ones are the decline in sperm quality and the daily environment and are used in many products, develop. Multiple genes that play a role in diabetes mellitus and cardiovascular diseases; increase in testicular cancer. including plastics, flame retardants, cosmetics and embryonic development of the testes are also 5. Endocrine related cancers have increased pesticides. involved in the developments of carcinoma in situ substantially in the last decades, including These problems arise from a maldevelopment of the of the testes: OCT3/4, SRY, SOX2, SOX17, KIT-ligand. testicular cancer, breast cancer, prostate cancer testes during early pregnancy, also known as The number of diseases potentially linked to early life Novel insights indicate a subtle interplay of specific and thyroid cancer; and testicular dysgenesis syndrome (TDS). Both in wildlife EDCs exposure is substantial and include; single nucleotide polymorphisms (SNPs), 6. Public awareness campaigns are needed to observations and in animal experiments TDS develops 1) obesity and diabetes. environmental factors, and epigenetic aberrations protect especially pregnant woman and young after exposure to EDCs, resulting in abnormal genital 2) female reproduction (premature ovarian failure, in the etiology of germ cell cancers. children against the harmful effects of EDCs. development, a short anogenital distance and female infertility). infertility. Data from ongoing longitudinal studies in 3) male reproduction (cryptorchidism, hypospadias, Late consequences of TDS References children confirm that our western lifestyle is a major male infertility, male hypogonadism). Male infertility and primary hypogonadism are 1. G.R. Dohle, S. Arver, C. Bettocchi, T.H. Jones, S. Kliesch,. contributing factor in the etiology of male genital 4) hormone-sensitive cancers in males and females related to health problems later in life. These men European Association of urology guidelines on male development disorders. (breast cancer, testicular cancer, ovary tumors, have an increased risk for obesity, type 2 diabetes hypogonadism. Update 2018. Uroweb.org/guidelines thyroid cancer). mellitus, cardiovascular disease and depression. 2. Skakkebaek NS, Rajpert-De Meyts E, Main KM. Testicular Male genital development 5) neurodevelopment and neuroendocrine systems Men with azoospermia have a 2.2 fold increased risk dysgenesis syndrome: an increasingly common The male genitalia develop between week 7 and week disorders (ADHD, Autism). of developing cancer later in life, including germ cell developmental disorder with environmental aspects. 14 of pregnancy. The activity of the sex region of the Y 6) Immune system defects (asthma, food allergies). cancers, prostate cancer and lymphomas. Poor Hum Reprod 2001; 16: 972-78. chromosome (SRY gene complex) results in semen quality and low testosterone are biomarkers 3. Gore AC, Chappell VA, Fenton SE, et. al. The Endocrine differentiation of the fetal gonad into a fetal testis. Many of these diseases will only appear later in life, for future health problems. Life expectancy is shorter Society’s Second Scientific Statement on Endocrine- Already early in pregnancy the fetal testis starts thus making it difficult to prove a causal relation with in these men. Disrupting Chemicals. Endocr Rev. 2015 Dec;36(6): producing hormones, like testosterone, anti- prenatal EDCs exposure. However, in the last years E1-E150. Muellerian hormone (AMH) and Insl-3 (Figure 1). both animal and human studies have strongly Action needed against EDCs 4. Levine H, Jørgensen N, Martino-Andrade A, Mendiola J, Testosterone plays a central role in the further indicated this relationship. Animal studies and The World Health Organization and the Endocrine Weksler-Derri D, Mindlis I, Pinotti R, Swan SH. Temporal differentiation of the male genitalia, either direct observation in wildlife provide strong evidence that Society have urged policymakers to take measures trends in sperm count: a systematic review and (development of the epididymis and vas deferens) or manmade chemicals can disrupt the hormone against EDCs. The estimated costs of inaction against meta-regression analysis. Hum Reprod Update. 2017 after conversion into dihydrotestosterone (DHT, dependent pathways responsible genital the effects of EDCs of male health in Europe are 1;23(6):646-659. development of the external genitalia and prostate). development. estimated to be 592 million euros per year (Nordic 5. van der Zwan YG, Biermann K, Wolffenbuttel KP, Cools Male under-virilization can be caused by different Council report 2014). Well-designed studies are M, Looijenga LH. Gonadal maldevelopment as risk factor defects in this system, including low fetal testosterone Consequences of TDS in adult life needed to show how EDCs exposures in early life are for germ cell cancer: towards a clinical decision model. production, absence of 5α-reductase and malfunction A decline in sperm quality has recently been the basis of many diseases later in life. Eur Urol. 2015;67(4):692-701. of the androgen receptor. confirmed by a large meta-analyses of more than 6. Eisenberg ML, Li S, Cullen MR, Baker LC. Increased risk of 5,000 publications: the authors found a 50–60% The Health commission of the EU has invited research incident chronic medical conditions in infertile men: Maldevelopment of the fetal testes and low fetal decline in sperm counts among men unselected by groups to initiate further investigations and 50 million analysis of United States claims data. Fertil Steril. testosterone production can result in birth defects, fertility from North America, Europe, Australia and euros are made available within the program Horizon 2016;105(3):629-636. like cryptorchidism and hypospadias. Later in life New Zealand, without signs of “leveling off” in more 2020 for this type of studies. However, more action is 7. Latif T, Kold Jensen T, Mehlsen J, Holmboe SA, Brinth L, these men will have small testes, low testosterone recent years (Levine et.al.). A recent study from China needed: we need to reduce and eliminate those EDCs Pors K, Skouby SO, Jørgensen N, Lindahl-Jacobsen R. production (congenital hypogonadism), defective in more than 30,000 young man found a decline in that have already been shown to be harmful for Semen Quality as a Predictor of Subsequent Morbidity: spermatogenesis and an increased risk for testicular sperm concentration of 35% in a 15-year study period. human health (Bisphenol A, DEHP, flame retardants, A Danish Cohort Study of 4,712 Men With Long-Term cancer (Figure 2). parabens, PCBs). Hundreds of manmade substances Follow-up. Am J Epidemiol. 2017 15;186(8):910-917. Studies in humans now also show a negative effect of in our daily environment have been indicated to act Epidemiology and etiology of TDS EDCs on male fertility: in a recent study the effects of as EDCs. Furthermore, public awareness needs to be Saturday, 17 March The incidence of cryptorchidism and hypospadias is pesticides exposure in early life resulted in a decline improved, such as explaining to pregnant women and 08.15- 10.00: Plenary Session 1. Hot topics, rising in some western countries. Both conditions of sperm quality of 30% later in life compared to men young mothers how to limit and avoid exposures to evidence quality and advances in andrology have mixed etiology, including genetic factors and that were not exposed. In the same period, we have EDCs. Campaigns have already been launched: www.

Figure 1.: Fetal development of the male genitalia

Figure 2. Adapted from: N.E. Skakkebaek et. al. Hum Reprod 2001: 16: 972-78. Fetal pituitary SRY gene

complex Environmental and life style factors Genetic defects LH FSH H HH Endocrine disrupting chemicals (EDCS) SRY gene complex, SOX genes

Leydig cells Fetal testis Sertoli cells

Testosterone INSL3 Anti-Müllerian Testicular dysgenesis syndrome (TDS) hormone (AMH) e

5α-reductase Regression of the Müllerian Sertoli cell dysfunction Leydig cell dysfunction ducts Impaired germ cell differentiation Androgen deficiency Differentiation Testicular Dihydrotestosterone of the

(DHT) Wolffian ducts descent

Differentiation of Male infertility Hypospadias the genital tubercle Epididymis Testicular Tumors Cryptorchidism and Vas deferens the urogenital sinus Congenital hypogonadism External genitalia Prostate

Figure 1.: Fetal development of the male genitalia Figure 2. Adapted from: N.E. Skakkebaek et. al. Hum Reprod 2001: 16: 972-78.

Saturday, 17 March 2018 EUT Congress News 5 Complications after open radical cystectomy Open RC remains most effective treatment despite complications risks

Prof. Georgios Gakis correlation was reported between pelvic venous Venous thromboembolism (VTE) improved perioperative gastrointestinal (GI) recovery 3 16,17 Department of pressure and central venous pressure . Continuous Postoperative venous thromboembolism (VTE) occurs and lower rates of GI complications . Urology and Pediatric norepinephrine administration resulted in lower in 2.5-10% of all patients undergoing radical Urology blood loss and rate of transfusions4. Moreover, in cystectomy for bladder cancer9-11. The wide range in In some studies additional benefits were reported Julius-Maximillians patients with neobladder, restrictive intraoperative reported rates is possibly related to an under-reporting with the adoption of ERAS protocols resulting in University of fluid management was associated with improved bias across different countries which, in turn, is likely shorter time intervals on intensive care units, lower Würzburg continence and potency results postoperatively5. due to under-registration of thromboemblic events rates of wound healing disorders and VTE events18. Würzburg (DE) after discharge in different health care systems. It is Moreover, a randomized study revealed that total Pulmonary complications important to note that the majority of thromboembolic parenteral nutrition for the first five days after surgery The occurence of pulmonary complications is often events occur after discharge of the patient10. resulted in higher number of postoperative associated with patient risk factors. Approximately complications which was mainly due to a higher rate 6% of patients develop postoperative pulmonary Risk factors for the development of VTE include a high of infectious complications19. Complications during or after radical cystectomy are complications after cystectomy. Risk factors for BMI, positive surgical margins, type of urinary frequent with delayed diagnosis and treatment postoperative pulmonary complications were reported diversion and prolonged duration of hospitalization10 Summary resulting in severe chronic morbidity. Therefore, its to be higher age (75 years and older), very low (<18.5) and non-O blood type11. Of the thromboembolic events Given the tumor aggressiveness of muscle-invasive management requires a high level of knowledge and or very high (>=30) body mass index (BMI), smoking, 40% of cases relate to deep vein thrombosis and 60% bladder cancer open radical cystectomy is nowadays experience as this surgical procedure may cause chronic obstructive pulmonary disease, insulin- to pulmonary embolism10. In various studies it was still the most effective treatment option for the severe morbidity in fourth of the patients with treated diabetes and low albulin levels (<3.5g/dL)6. consistently reported that extended duration of treatment of muscle-invasive bladder cancer. The mortality rates rapidly increasing with complications1. Therefore, some efforts have been undertaken to thromboprophylaxis using low-molecular weight increasing use of neodjuvant and adjuvant treatment This article summarizes recent studies with high level reduce the risk of pulmonary complications heparin derivates for four weeks after discharge modalities mandates further attempts to reduce the of evidence in this field. postoperatively. One strategy that has been reduces the relative risk of VTE by approximately rate and severity of perioperative complications. investigated was to compare the rate of complications 70%12 while the risk of delayed bleeding during Intraoperative blood loss using either a low vs. high positive end-exspiratory extended treatment is low13. Importantly, a recent In recent years an increasing number of randomized Open radical cystectomy is still the mainstay of pressure and alveolar recruitment manoeuvres during study also revealed that thromboembolic events are trials have addressed critical issues of perioperative treatment for muscle-invasive bladder cancer1. surgery. Looking into the literature there is divergent more frequent in patients receiving neoadjuvant care. Further well-designed trials are warranted in It has been consistently reported that open radical data on whether this anesthesiologic strategy during chemotherapy for muscle-invasive bladder cancer this major urological field of surgery to improve our cystectomy, as a major surgical procedure, is surgery may have beneficial effects on pulmonary (17%) supporting the use of agents for understanding in refinements of perioperative care associated with a higher estimated blood loss function postoperatively. thromboembolic prophylaxis during chemotherapy14. for improved functional and oncological outcomes during surgery compared to robotic cystectomy2. after cystectomy. Therefore, reducing blood loss has come to the In the largest study, Hemmes et al. did not find a Gastrointestinal complications focus of surgeons experienced in open significant impact of this manoeuvre on outcomes The construction of urinary diversion is the main Editorial Note: Due to space constraints, the techniques. after major abdomimal surgery. On the contrary, reason for postoperative complications after reference list can be made available to interested Easy and intuitive PDD in Precision Modularitya trend towards improved Flexibility outcomes S-Technologies was noted cystectomy. 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Flexibility TP 61 2.0 02/2018/A-E S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility Ergonomic Intuitive S-TECHNOLOGIES PDD in Precision Flexibility Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Tech- nologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modu- larity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergono- mic Easy Stopand intuitive Guessing. PDD in Precision Modularity Start Flexibility Knowing. S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies PDD in PrecisionErgonomic Easy and intuitive Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity PDDFlexibility – S-Technologiesflexibility in Ergonomic visualization Easy and withintuitive IMAGE1 PDD in Precision S™ Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergo- nomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy S-Tech- nologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modu- larity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergono- mic Easy KARLand STORZ intuitive SE & Co. PDD KG, Dr.-Karl-Storz-Straße in Precision Modularity 34, 78532 Tuttlingen/Germany, Flexibility www.karlstorz.comS-Technologies PDD in PrecisionErgonomic Easy and intuitive Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy

6 EUT Congress News Saturday, 17 March 2018 Novel antibiotics in treating Urinary Tract Infections Antimicrobial stewardship is crucial to maintain efficacy of current antibiotic agents

Assoc. Prof. Kurt G. ceftazidime/avibactam vs doripenem was Naber demonstrated for the FDA co-primary endpoints Department of (symptomatic resolution/microbiological eradication Urology at test of cure (TOC): 280 of 393 (71.2%) vs 269 of 417 Technical University (64.5%) patients (difference, 6.7% [95%CI, 0.3% to of Munich 13.1%]). Munich (DE) Microbiological eradication at TOC occurred in 304 of 393 (77.4%) ceftazidime/avibactam vs 296 of 417 (71.0%) doripenem patients (difference, 6.4% [95% CI, 0.3% to 12.4%]), demonstrating superiority at the 5% significance level. Both treatments Co-Author: Florian M.E. Wagenlehner, Clinic for showed similar efficacy against ceftazidime- Urology, Pediatric Urology and Andrology, Justus nonsusceptible pathogens. Ceftazidime/avibactam Figure 1: Global and regional resistance rates of uropathogens (total spectrum) in health-care associated urinary tract infections Liebig University, Giessen (DE) had a safety profile consistent with that of (HAUTI)2 ceftazidime alone. Thus, ceftazidime-avibactam was Antibiotic resistance in Gram-negative uropathogens highly effective for the empiric treatment of cUTI/ is increasing worldwide. A compilation of worldwide APN and may offer an alternative to carbapenems in participants with IMP- and colistin-resistant eradication, clinical, and composite (microbiological studies showed resistance rates of Gram-negative this setting8. pathogens received open-label IMP/CS - relebactam and clinical) cure rates at the end-of-IV therapy (EOIV) uropathogens against fluoroquinolones in 10 to 80%, (200mg/100mg to 500mg/250mg) IV q6h. Treatment and TOC (Day 15-19) in mMITT population were against cephalosporines in 5 to 70% and against 3. Meropenem / Vaborbactam duration: five to 21 days. (https://clinicaltrials.gov/ct2/ analyzed for cUTI and APN subgroups. At TOC, PLZ carbapenems in 0 to 35%1. Vaborbactam is a novel cyclic boronic acid inhibitor of show/NCT02452047). achieved higher composite cure rates than many class A and class C enzymes. It is a potent meropenem in cUTI (84/107=78.5% vs. 82/119=68.9%; A specific surveillance study in urology is the Global inhibitor of serine carbapenemases, and KPC in 5. Cefiderocol difference 9.6 (95%CI; -2.6 to 21.3) and APN Prevalence of Infections in Urology (GPIU), which is a particular. In-vitro data suggest that meropenem- Cefiderocol (S-649266) is a novel parenteral (72/84=85.7% vs. 56/78=71.8%; difference 13.9 worldwide point prevalence study performed every vaborbactam (M-V) is highly active against KPC- siderophore cephalosporin conjugated with a catechol (95%CI;0.4 to 27.1), driven by higher microbiological November since 2003. This study is intended to create producing Enterobacteriaceae. Little effect on A. moiety at the third-position side chain. Cefiderocol eradication rates in each subgroup. The incidence of surveillance data in patients at urological baumannii containing OXA-type carbapenemases was utilizes a novel mechanism of entry into the AEs, including SAEs and AEs leading to departments with health-care associated urinary tract observed7,9. periplasmic space of Gram-negative bacteria and is discontinuation of IV study drug, was low and infections (HAUTI)2. Resistance rates of most broadly stable to ESBLs and carbapenemases. The in comparable between treatment arms20. uropathogens against all tested antibiotics were high, A phase-3 study (TANGO-1) evaluated the efficacy, vitro activity of cefiderocol against Pseudomonas particularly with regards multidrug resistance safety, and tolerability of M-V (Vabomere®) compared aeruginosa was enhanced under iron-depleted 7. Finafloxacin (Figure 1). In many countries the resistance rate of to piperacillin/tazobactam (P-T) in the treatment of conditions, whereas that of ceftazidime was not Finafloxacin, an investigational fluoroquinolone, Gram-negative uropathogens only against cUTI/APN in adults. M-V (meropenem 2 g plus affected. Cefiderocol was shown to have potent suitable for IV and oral administration, is being carbapenems is below 10%, a threshold used for vaborbactam 2 g), administered IV q8h vs P-T chelating activity with ferric iron, and extracellular developed as sequential therapy of bacterial empiric therapy of severe infections, such as (piperacillin 4 g plus tazobactam 0.5 g), q8h. After a iron was efficiently transported into P. aeruginosa infections including UTIs. The compound exhibits urosepsis. A worrying finding in the GPIU study was minimum of 15 IV doses LVX 500mg could be cells in the presence of cefiderocol as well as good activity against Gram-positive, Gram-negative also that the severity of HAUTI is also increasing, 25% administered orally q24h, if clinically indicated. Total siderophores. Cefiderocol forms a chelating complex and anaerobic pathogens with a bactericidal being urosepsis in recent years. treatment was 10 days, unless a participant had with iron, which is actively transported into P. mechanism of action, a high level of excretion in the baseline bacteremia where up to 14 days of therapy aeruginosa cells via iron transporters, resulting in urine and increased potency at acidic pH21. Need for novel antibiotics could be administered IV. (https://clinicaltrials.gov/ potent antibacterial activity of cefiderocol against P. Although for uncomplicated cystitis old antibiotics, ct2/show/NCT02166476). aeruginosa14. In a phase-2 trial finafloxacin (IV and oral) was such as fosfomycin trometamol, nitrofurantoin, examined for a total of five days (FINA05) or 10 days pivecillinam, and nitroxoline are still recommended Of 550 subjects randomized, 374(68.0%) included In total, 189 non-fermentative Gram-negative bacteria (FINA10) versus ciprofloxacin (IV and oral) for 10 days as first-line3,4, for complicated and especially HAUTI in m-MITT (165/192[85.9%] in M-V and (107 Acinetobacter baumannii and 82 Pseudomonas (CIPRO10) for the treatment of cUTI/APN. Patients novel antibiotics need to be developed. Several 154/182[84.6%] in P-T groups had baseline aeruginosa ) and 282 Enterobacteriaceae were were randomized 1:1:1 into one of the three treatment strategies are currently employed in the development Enterobactericeae. Mean duration of IV therapy was studied. Cefiderocol exhibited greater antimicrobial arms. The study lasted 24±2 days with examinations of novel antibiotics: Beta-lactam/Beta-lactamase eight days. At the end of IV treatment clinical cure activity in vitro against carbapenem-resistant on Day 3, on 10±2 and 17±2 days (TOC). inhibitor combinations are extended to was observed with M-V in 162/165=98.2% and with Gram-negative bacteria than several comparator cephalosporins and also carbapenems. So called P-T in 147/154=95.5% of the patients. antibiotics15. The treatment success (combined clinical and siderophore antibiotics (beta-lactams) are tested. Microbiological eradication was found in microbiological response) for the m-ITT population Novel aminoglycosides, novel fluoroquinolones and 161/165=97.6% with M-V and 142/154=92.2% with In a phase-2 study efficacy and safety of IV TOC was 70.3%(95%CI: 57.6%-81.1%) in the FINA05 novel tetracyclines are also in clinical development. P-T. Clinical outcomes were >90% across all MICs. cefiderocol versus IV IMP/CS was tested in group, 67.6%(55.2 78.5%) in the FINA10 group and hospitalized adults with cUTI/APN. Patients with 57.4%(44.1%-70.0%) in the CIPRO10 group. 1. Ceftolozane / Tazobactam Although 19.5% of baseline Enterobacteriaceae Gram-negative pathogens were randomized 2:1 to Finafloxacin dosed for five or 10 days showed higher Ceftolozane/tazobactam is a novel cephalosporin isolates were non-susceptible to P-T, clinical and receive cefiderocol(2 g) IV q8h, or high-dose IMP/ treatment success rates than ciprofloxacin dosed for combined with an established beta-lactamase inhibitor microbiologic outcomes were similar for subjects with CS (1g/1 g) IV q8h, for seven to 14 days. Of the 452 10 days. The microbiological eradication rate of (BLI). This drug has in-vitro activity against multidrug- susceptible and non-susceptible isolates10. The most patients randomized, 448 were treated and 371 of ciprofloxacin was lower in patients with acidic resistant strains of Pseudomonas aeruginosa and other common adverse reactions in patients taking M-V the micro-ITT population were assessed for urine- pH as compared to those with alkaline common Gram-negative pathogens, including most were headache, infusion site reactions and diarrhea. efficacy. urine-pH, while finafloxacin’s microbiological ESBL-producing Enterobacteriaceae spp. M-V is associated with serious risks including allergic eradication rate was equally high at either pH range reactions and seizures11. Cefiderocol met the FDA primary efficacy endpoint of on Day 3. The safety profiles of the three treatment In a phase-3 study ceftolozane/tazobactam was composite of clinical cure and microbiologic groups were equivalent and the majority of the AEs compared with levofloxacin (LVX) in hospitalized TANGO-2 trial including also cUTI/APN caused by eradication at TOC in 72.6% of patients(n=252) which were mild to moderate in severity and regarded to be patients with complicated UTI (cUTI) or acute carbapenem-resistant Enterobacteriaceae (CRE) was superior to IMP/CS at 54.6%(n=119), difference unrelated to study medication21. pyelonephritis (APN). Patients were randomly stopped early for superior benefit-risk with M-V 18.58% (95%CI: 8.23, 28.92). Cefiderocol was well assigned 1:1 to receive 1.5g intravenous (IV) compared to best available therapy for CRE12. tolerated; 40% of patients experienced an adverse 8. Eravacycline ceftolozane-tazobactam q8 h or 750mg IV LVX qd, event (AE) with cefiderocol vs 50% of patients with Eravacycline is a novel synthetic fluorocycline that is both for seven days. Of 1083 patients enrolled, 4. Imipenem /Relebactam IMP/CS. Serious adverse events (SAEs) occurred in 14 active against most Gram-negative species. In vitro 800(73.9%), of whom 656(82.0%) had APN, were Relebactam is a non-beta-lactam serine BLI, similar patients (4.7%) who received cefiderocol and 12 eravacycline is two- to four-fold more potent than included in the m-MITT population. Ceftolozane/ to avibactam, that has inhibitory activity against class patients (8.1%) who received IMP/CS16. tigecycline against CRE7. tazobactam was non-inferior to LVX for composite A and C beta-lactamases. In vitro assays with (microbiological/clinical) cure (306[76.9%] of 398 carbapenem-resistant Enterobacteriaceae isolates 6. Plazomicin A phase-3 study evaluating eravacycline 1.5mg/kg vs. 275[68.4%] of 402, 95%CI 2,3-14.6) and, as the demonstrated that MICs were significantly lowered Plazomicin (PLZ) is a novel aminoglycoside that was versus 750mg LVX for the treatment of cUTI/APN lower bound of the 95%CI was >0, superiority was when imipenem(IMP) was tested with relebactam synthetically derived from sisomicin. Like other (IGNITE2) with an oral step-down did not achieve indicated. Adverse event profiles were similar in against KPC-producing K. pneumoniae. Compared to aminoglycosides, it is a bactericidal agent that works non-inferiority. These data remain unpublished to the two treatment groups and were mainly IMP alone, little reduction in imipenem-relebactam primarily through inhibition of protein synthesis. PLZ date and thus further studies are needed to establish non-serious. Thus, ceftolozane/tazobactam led to MICs were noted in OXA-48-producing K. is structurally similar to the traditional the role of eravacycline in treating CRE7. better responses than high-dose LVX in patients pneumoniae or OXA-23-producing A. baumannii, aminoglycosides (amikacin, gentamicin, tobramycin), with cUTI/APN5. suggesting that relebactam, unlike avibactam, does though was modified to resist aminoglycoside- Crucial role of antimicrobial stewardship not have significant activity against the class D modifying enzymes that are often present in CRE. PLZ Several antibiotic substances are currently upon 2. Ceftazidim /Avibactam enzymes7,9. Phase 2 clinical trials investigating the is not affected by carbapenemase production and has marketing, or in the late clinical phase of Avibactam, a non–beta-lactam BLI, restores the safety, tolerability, and efficacy of IMP/CS-relebactam good in-vitro activity against carbapenem-resistant development. Nevertheless, unique novel substances activity of ceftazidime against Ambler class A (eg,ESBL in treating complicated urinary tract infections and isolates of K. pneumoniae, E. coli, and Enterobacter are rare, therefore antimicrobial stewardship plays an and KPC), class C (eg, AmpC), and some class D complicated intra-abdominal infections have been species producing a variety of carbapenemases and important role to preserve the antibiotic substances beta-lactamase–producing bacteria. It is not active completed13. ESBLs. The presence of 16S rRNA methyltransferase in available. against metallo-beta-lactamases6,7. Enterobacteriaceae, which modifies the ribosomal site A phase-3 trial (RESTORE-IMI-1) is underway that binds PLZ, leads to plazomicin resistance. PLZ is Editorial Note: Due to space constraints the reference RECAPTURE 1 and 2 comprised two identical phase-3 investigating efficacy and safety of IMP/CS + more potent than other aminoglycosides in treating list has been omitted. Interested readers can email at studies in patients with cUTI/APN. Eligible patients relebactam vs colistin + IMP/CS for cUTI/APN due to Enterobacteriaceae7,17,18. [email protected] for a complete listing. were randomized 1:1 to IV ceftazidime-avibactam IMP-resistant pathogens. Group 1: IMP/CS - 2000 mg/500 mg every 8 hours or IV doripenem 500 relebactam IV (200mg/100mg to 500mg/250mg A phase-2 study was performed in patients with cUTI/ Saturday 17 March mg every eight hours. Of 1033 randomized patients, depending on renal function) q6h and placebo APN compared PLZ with LVX19. In a phase-3 study 10.00-14.00: Joint meeting of the EAU Section 393 and 417 treated with IV ceftazidime/avibactam colistimethate sodium (CMS) IV q12h. Group 2: CMS (EPIC) hospitalized patients with cUTI/APN received IV of Andrological Urology (ESAU) and the EAU and IV doripenem, respectively, were eligible for the [colistimethate base activity (CBA) 300mg] IV loading PLZ (15mg/kg q24h) or IV meropenem (1g q8h) for Section of Infections in Urology (ESIU); When primary efficacy analyses; 19.6% had ceftazidime- dose, followed by CBA 75mg to 150mg) IV q12h and four to seven days, followed by optional oral therapy, basic science meets clinical practice nonsusceptible baseline pathogens. Non-inferiority of IMP/CS (200mg to 500mg) IV infusion q6h. Group 3: for a total of seven to 10 days. Microbiological

Saturday, 17 March 2018 EUT Congress News 7 Novel modalities for nodal staging in prostate cancer Burden of nodal disease is linked with poorer outcomes

Dr. Henk van der Poel Moreover, molecular staging by RT-PCR showed nodal 4. Thoeny HC, Barbieri S, Froehlich JM, Turkbey B, Choyke Dept. of Urology metastases in up to 30% of men with routinely- PL. Functional and Targeted Lymph Node Imaging in Netherlands Cancer assessed node negative disease and these men were Prostate Cancer: Current Status and Future Challenges. Institute at risk of disease recurrence13,14. On the other hand, Radiology. 2017;285(3):728-43. Amsterdam (NL) 68Ga-PSMA-PET scanning had high accuracy in 5. Udovicich C, Perera M, Hofman MS, Siva S, Del Rio A, detecting non-local recurrences after radical Murphy DG, et al. (68)Ga-prostate-specific membrane prostatectomy8 even at PSA levels below 0.5 ng/ml. antigen-positron emission tomography/computed This indicates that PSMA-PET scanning may help to tomography in advanced prostate cancer: Current state select men for salvage local radiotherapy after and future trends. Prostate Int. 2017;5(4):125-9. prostatectomy9,10. 6. Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, Specificity, and Predictors of Surgery Positive 68Ga-Prostate-specific Membrane Antigen Co-Author: Dr. Nikos Grivas (GR) From surgical studies on lymph node dissection we Positron Emission Tomography in Advanced Prostate already know that the removal of more nodes during Cancer: A Systematic Review and Meta-analysis. In prostate cancer, nodal metastases are an initial an (extended) lymph node dissection results in a European urology. 2016. step in the development of distant disease in the vast higher yield of nodal metastases and potentially 7. Jilg CA, Drendel V, Rischke HC, Beck T, Vach W, Schaal K, majority of men. Moreover, disease recurrence after longer biochemical recurrence-free survival1,11. Even et al. Diagnostic Accuracy of Ga-68-HBED-CC-PSMA- local therapy is most frequently caused by the though an extended dissection of nodal tissue may Figure 2: ICG provides intraoperative near infra-red (NIR) Ligand-PET/CT before Salvage Lymph Node Dissection for presence of nodal metastases. These observations result in better outcome when compared to no or imaging of lymph nodes Recurrent Prostate Cancer. Theranostics. 2017;7(6): supported the notion that nodal metastases do limited dissection, still the addition of adjuvant 1770-80. develop early in the progression process of prostate radiotherapy and androgen ablation further improved 8. van Leeuwen PJ, Stricker P, Hruby G, Kneebone A, Ting F, cancer. outcome1. We therefore studied the role of a lymph drainage Thompson B, et al. (68) Ga-PSMA has a high detection tracer to direct extended lymph node dissection and rate of prostate cancer recurrence outside the prostatic Nodal metastases and survival These observations from retrospective series seem to we observed both an improved nodal metastases fossa in patients being considered for salvage radiation Still the precise moment of nodal metastases support two notions: a. that imaging of all relevant yield as well as decreased biochemical recurrence treatment. BJU international. 2016;117(5):732-9. development remains illusive. Yet, understanding nodal metastases is not feasible with current rates in comparison to a historic control population14. 9. Schmidt-Hegemann NS, Fendler WP, Buchner A, Stief C, how and when nodal disease develops is crucial in imaging modalities; b. that complete ablation of Rogowski P, Niyazi M, et al. Detection level and pattern understanding cancer progression and determining nodal metastases will require more than removing Prognosis prediction of positive lesions using PSMA PET/CT for staging prior timing of treatment as opposed to active surveillance. visible metastases only. Considering these Older studies showed a non-linear correlation to radiation therapy. Radiat Oncol. 2017;12(1):176. Prognosis of men with nodal metastases-only is far observations it can be assumed that, although between androgen receptor expression in nodal 10. Calais J, Czernin J, Cao M, Kishan AU, Hegde JV, better than that for men with metastases to other imaging may direct treatment to specific nodal zones metastases and overall survival15. For Shaverdian N, et al. (68)Ga-PSMA PET/CT mapping of sites and the majority of men are alive 10 years after where metastases are most likely, better predictors immunohistochemical detection of lymph node prostate cancer biochemical recurrence following radical diagnosis15,19. Moreover, recent analyses suggested a of nodal metastases are needed to fully eradicate metastases from prostate cancer Queisser et al.16 prostatectomy in 270 patients with PSA<1.0ng/ml: Impact survival benefit of early nodal metastases treatment1,2. remnant disease. The same seems to apply to the use suggested to use PSA, PSMA and androgen receptor on Salvage Radiotherapy Planning. Journal of nuclear The number of removed nodes as well as the number of radio-guided-PSMA tracer directed surgery as expression. In light of PSMA tracing it is interesting to medicine : official publication, Society of Nuclear of nodes containing metastases is predictive of recently very elegantly introduced by the group of note that the percent of PSMA-positive cells was Medicine. 2017. survival outcome15,19,20. Tobias Maurer12. similar for primary tumor and nodal metastases, but 11. Abdollah F, Karnes RJ, Suardi N, Cozzarini C, Gandaglia the levels of expression per cell were lower in nodal G, Fossati N, et al. Predicting survival of patients with Imaging Although interesting to guide towards nodes most metastases17. node-positive prostate cancer following multimodal In prostate cancer, nodal metastases conventional likely to contain metastases, this method still will treatment. European urology. 2014;65(3):554-62. imaging has long been limited due to its inadequacy leave untreated the nodal metastases which are Bostrom et al.18 reported that although PTEN loss 12. Rauscher I, Duwel C, Wirtz M, Schottelius M, Wester HJ, to detect pelvic nodal lesions smaller than 7-8mm. under the detection threshold. A nodal-template was an independent predictor of outcome in men Schwamborn K, et al. Value of (111) In-prostate-specific Therefore, current guidelines do not recommend directed treatment rather than targeting visible nodal with node positive disease, TMPRSS2:ERG fusion membrane antigen (PSMA)-radioguided surgery for imaging for nodal staging in localized prostate metastases could improve outcome. This would not status was not. Cell proliferation had an additional salvage lymphadenectomy in recurrent prostate cancer: cancer3. only apply to men with macroscopic nodal prognostic value to the number of positive nodes19. correlation with histopathology and clinical follow-up. metastases but might also improve outcome in men Interestingly, neuroendocrine differentiation as BJU international. 2017;120(1):40-7. With the advent of novel imaging modalities, even with microscopic or molecular metastases where a assessed by chromogranin A expression was found 13. Wit EM, Acar C, Grivas N, Yuan C, Horenblas S, Liedberg metastases of 2mm can be detected using either benefit may even be higher as implied by the more frequently in nodal metastases (2.6% of cells) F, et al. Sentinel Node Procedure in Prostate Cancer: A 68Ga-PSMA-PET or USPIO (nano-)MRI4. Sensitivity of observation that men with less nodal metastases compared to the primary tumor (1%), in particular Systematic Review to Assess Diagnostic Accuracy. 68Ga-PSMA-PET scanning was found around 60% have generally better outcome after surgical in Gleason pattern 5 tumors (7.8% vs 1.4% of European urology. 2017;71(4):596-605. whereas specificity is generally reported over 95%5. treatment. cells)20. 14. Grivas N, Wit E, Pos F, de Jong J, Vegt E, Bex A, et al. In a systematic review solely on studies using Sentinel Lymph Node Dissection to Select Clinically 68Ga-PSMA-11 PET tracing (Figure 1), positive scans Nodal template Clearly, management of nodal metastases in prostate Node-negative Prostate Cancer Patients for Pelvic were more frequently encountered in studies Non-tumor specific tracers depicting nodal drainage cancer is still in its infancy. Routine radiation of nodal Radiation Therapy: Effect on Biochemical Recurrence and including men with recurrent disease compared to patterns such as those applied in the sentinel node basins in localized prostate cancer was not associated Systemic Progression. International journal of radiation those with primary disease6 Jilg et al. found biopsy method have the potential to tailor nodal with improved survival21 but selective radiation of oncology, biology, physics. 2017;97(2):347-54. remarkably high sensitivity of 94% when the results surgery, in particular, in those men with increased areas most likely to contain or even have proven 15. Sweat SD, Pacelli A, Bergstralh EJ, Slezak JM, Cheng L, were assessed on the main nodal regions7 but this risk of nodal metastases where novel imaging nodal disease was shown to be associated with a Bostwick DG. Androgen receptor expression in prostate dropped to 81% in the sub-regions indicating that methods such as USPIO-enhanced mpMRI and better than expected recurrence-free outcome2,14. cancer lymph node metastases is predictive of outcome removal of only PET-positive nodes would result in 68Ga-PSMA- PET fail to reveal macroscopic after surgery. The Journal of urology. 1999;161(4):1233-7. under-sampling. metastases and the proper template remains illusive. Moreover, the true role of nodal dissection is still 16. Queisser A, Hagedorn SA, Braun M, Vogel W, Duensing debated22. A nomogram to predict outcome showed S, Perner S. Comparison of different prostatic markers in Mean size of positive nodes was as high as 8.5mm These lymph node tracers currently consist of both that presence of Gleason sum score > 7 was the lymph node and distant metastases of prostate cancer. whereas false negative nodal metastases still had a radionuclides such as 99Tc and fluorophores such as strongest risk factor predicting cancer-specific survival Mod Pathol. 2015;28(1):138-45. mean size of 3.8mm7. From studies on lymph node indocyanine green (ICG). The former allowing for in men with nodal metastases. These men were 5x 17. Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate- dissection in early nodal metastasized prostate cancer lymph drainage imaging preoperatively using more likely to die of disease11. In the same series, with specific membrane antigen expression is greatest in it became apparent that one in five metastases found scintigraphy, whereas ICG provides intraoperative each positive node removed cancer-specific mortality prostate adenocarcinoma and lymph node metastases. on routine immunohistochemistry are smaller than near infra-red (NIR) imaging29 (Figure 2). In a increased by 10%. Urology. 1998;52(4):637-40. 2mm12. There is no sign whatsoever that the 2mm systematic review the diagnostic accuracy of sentinel 18. Bostrom PJ, Bjartell AS, Catto JW, Eggener SE, Lilja H, cutoff is associated with a clinically relevant nodal node techniques far exceeded that of any preoperative Locally treating nodal metastases Loeb S, et al. Genomic Predictors of Outcome in Prostate metastases. Therefore, at the moment by definition imaging technique for the detection of nodal In prostate cancer an increase in the burden of nodal Cancer. European urology. 2015;68(6):1033-44. 68Ga-PSMA-PET scanning will, always underestimate metastases with the extended lymph node dissection disease is associated with poorer outcome. Local 19. Cheng L, Pisansky TM, Sebo TJ, Leibovich BC, Ramnani nodal metastases presence. as reference standard13. treatment of nodal metastases with surgery or DM, Weaver AL, et al. Cell proliferation in prostate cancer radiotherapy may improve outcome, but clinical and patients with lymph node metastasis: a marker for in particular molecular predictors are only poorly progression. Clin Cancer Res. 1999;5(10):2820-3. understood. Template-guided surgery based on novel 20. Genitsch V, Zlobec I, Seiler R, Thalmann GN, Fleischmann pre- and intraoperative imaging may improve nodal A. Neuroendocrine Differentiation in Metastatic dissection. Conventional Prostate Cancer Is Significantly Increased in Lymph Node Metastases Compared to the Primary References Tumors. Int J Mol Sci. 2017;18(8). 1. Touijer KA, Karnes RJ, Passoni N, Sjoberg DD, Assel M, 21. Muller AC, Eckert F, Paulsen F, Zips D, Stenzl A, Schilling Fossati N, et al. Survival Outcomes of Men with Lymph D, et al. Nodal Clearance Rate and Long-Term Efficacy of Node-positive Prostate Cancer After Radical Individualized Sentinel Node-Based Pelvic Intensity Prostatectomy: A Comparative Analysis of Different Modulated Radiation Therapy for High-Risk Prostate Postoperative Management Strategies. European Cancer. International journal of radiation oncology, urology. 2017. biology, physics. 2016;94(2):263-71. 2. James ND, Spears MR, Clarke NW, Dearnaley DP, Mason 22. Colicchia M, Sharma V, Abdollah F, Briganti A, Jeffrey MD, Parker CC, et al. Failure-Free Survival and Karnes R. Therapeutic Value of Standard Versus Extended Radiotherapy in Patients With Newly Diagnosed Pelvic Lymph Node Dissection During Radical Nonmetastatic Prostate Cancer: Data From Patients in the Prostatectomy for High-Risk Prostate Cancer. Curr Urol Control Arm of the STAMPEDE Trial. JAMA Oncol. Rep. 2017;18(7):51. 2016;2(3):348-57. 3. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch Friday 16 March MG, De Santis M, et al. EAU-ESTRO-SIOG Guidelines on 12.30-15.45: Joint Session of the European Prostate Cancer. Part 1: Screening, Diagnosis, and Local Association of Urology (EAU) and the Korean Treatment with Curative Intent. European urology. Urological Association (KUA) Figure 1: A scan using 68G-PSMA PET tracing 2017;71:618-29.

8 EUT Congress News Saturday, 17 March 2018 Precision medicine in bladder cancer How can we precisely select the best systemic treatment?

Asst. Prof. Günter biomarkers are a recently proposed 20-gene model Niegisch predicting the likelihood of lymphnodal disease as Department of well as a recently proposed risk model developed Urology by an integrated analysis of the TCGA data2,12. Medical Faculty Heinrich-Heine- In addition, predictive biomarkers will help to University delineate the optimal therapy to each individual Düsseldorf (DE) patient. In retrospective analyses of patients undergoing platinum-based neoadjuvant chemotherapy, the potential value of predictive biomarkers has already been demonstrated. As example, response to neoadjuvant chemotherapy has Following a recent suggestion by the American been demonstrated to be dependent on molecular Society of Clinical Oncology (ASCO), precision subtypes of bladder cancer4,13. medicine in oncology aims to improve efficacy, to minimize side effects and to overcome acquired However, these data lack prospective evaluation. resistance of anti-cancer therapies by delivering Further, even with an appropriate predictive ”the right cancer treatment to the right patient at the subtype, a significant number of patients will not right dose and the right time”1. benefit from neoadjuvant chemotherapy nevertheless. Lastly, it remains unclear if any Figure 1: Diagnostic and therapeutic algorithm as proposed by the TCGA consortium as a framework for prospective hypothesis To achieve these aims, appropriate prognostic and systemic treatment should be offered to patients testing in clinical trials2 predictive biomarkers are required. Prognostic who are assumed to be non-responders based on biomarkers may stratify patients according to their their molecular subtype. individual risk in order to decide whether systemic in urothelial urinary bladder cancer. Cancer Control, 2013. “...it remains unclear if any systemic therapy is justified balancing potential toxicities With regard to the latter point, integration of 20(3): p. 200-10. treatment should be offered to against potential benefits (“who to treat”). high-throughput data may predict individual 8. Bellmunt, J., et al., Pembrolizumab as Second-Line Predictive biomarkers may predict treatment treatment approaches beyond conventional systemic Therapy for Advanced Urothelial Carcinoma. N Engl J patients who are assumed to be responses to be expected by individual treatment therapy as well. Only recently, the TCGA consortium Med, 2017. 376(11): p. 1015-1026. non-responders based on their approaches (“how to treat”). proposed a potential diagnostic and therapeutic 9. Sharma, P., et al., Nivolumab in metastatic urothelial treatment workflow based on their multi-platform carcinoma after platinum therapy (CheckMate 275): a molecular subtype.” Clinical use of appropriate biomarkers not only analyses identifying key drivers within the specific multicentre, single-arm, phase 2 trial. Lancet Oncol, 2017. requires their identification by modern “pan-omics” molecular subtypes (Figure 1). 18(3): p. 312-322. 13. Choi, W., et al., Identification of distinct basal and methods (whole-genome sequencing, transcriptome 10. Rosenberg, J.E., et al., Atezolizumab in patients with luminal subtypes of muscle-invasive bladder cancer with analysis, proteomic and metabolomics approaches) Next to conventional chemotherapy, novel locally advanced and metastatic urothelial different sensitivities to frontline chemotherapy. Cancer but also their bioinformatic and functional integration antineoplastic treatment (immune-oncological carcinoma who have progressed following treatment Cell, 2014. 25(2): p. 152-65. in the pathophysiologic framework of the according approaches, FGFR3 inhibitors, other targeted with platinum-based chemotherapy: a single-arm, neoplastic disease. agents) have been included in this proposal as multicentre, phase 2 trial. Lancet, 2016. 387(10031): Saturday 17 March well. However, both preclinical as well as clinical p. 1909-20. 10.15-14.00: Joint meeting of the EAU Section of Precision oncology approaches have already been validation is needed before translation into clinical 11. Faltas, B.M., et al., Clonal evolution of chemotherapy- Urological Imaging (ESUI), the EAU Section of adopted or are getting more and more adopted practice is possible. resistant urothelial carcinoma. Nat Genet, 2016. 48(12): p. Uropathology (ESUP) and the EAU Section of regarding the treatment of a variety of malignancies 1490-1499. Urological Research (ESUR) (e.g. chronic myelogenous leukaemia, breast cancer, 12. Smith, S.C., et al., A 20-gene model for molecular nodal How tumour heterogeneity influences our advanced non–small cell lung cancer). Recent “Future precision oncology staging of bladder cancer: development and prospective practice today and tomorrow high-throughput analyses may provide the scientific approaches are likely to focus first assessment. Lancet Oncol, 2011. 12(2): p. 137-43. basis for a potential future implementation of precision oncology in the treatment of bladder cancer on perioperative therapy before as well2-4. according options in the metastatic Currently, unselected platin-based combination setting may become tangible.” therapies are the mainstay both in the curative perioperative systemic treatment of muscle-invasive non-metastatic bladder cancer as well as in palliative Intra-tumor heterogeneity treatment of non-resectable or metastatic bladder While advances in precision oncology in the cancer. However, neoadjuvant (NAC) or adjuvant (AC) perioperative systemic treatment of bladder cancer perioperative chemotherapy, using cisplatin-based clinical may be expected in the medium term, UROLOGY regimes, improves oncological outcome only implementation in the metastatic, especially in the marginally (<10% improvement in five-year overall post-platinum, setting may be limited not only by survival)5,6. inter- but also by intra-tumor heterogeneity. CLEARLY

In the palliative setting, initial responses are observed In this context, a recent comparative analysis of DEFINED only in up to 70% of patients and long term-survival primary and metastatic tumor tissue before and is below 20%7. These observations in perioperative after platin-based chemotherapy demonstrated the and palliative systemic treatment imply that in many evolution of distinct molecular features during UC patients a subpopulation of cancer cells evades growth and metastasis as well as before and after cytostasis or cell death by inherent or acquired systemic therapy11. resistance to systemic treatments. This is apparently also true for recently introduced immune-oncological In summary, important initial steps towards approaches as only about 25% of patients respond8-10. precision oncology in bladder cancer therapy have been taken. Nevertheless, validation of these data Precision oncology as well as integration of these data in the Recent high-throughput analyses may provide the pathophysiologic mainframe of bladder cancer in scientific basis for a potential future order to allow tailoring individual diagnostic and implementation of precision oncology in the therapeutic approaches are essential. treatment of bladder cancer as well and may improve treatment outcomes2-4. However, validation References of these data in a prospective clinical setting is still 1. Schwartzberg, L., et al., Precision Oncology: Who, How, missing as is integration of a substantial part of What, When, and When Not? Am Soc Clin Oncol Educ these data in the mainframe of pathophysiology of Book, 2017. 37: p. 160-169. bladder cancer. 2. Robertson, A.G., et al., Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. Cheers! Further, available data from these analyses as well Cell, 2017. 171(3): p. 540-556 e25. as of other projects is largely restricted to primary 3. Sjodahl, G., et al., Molecular classification of urothelial cancer tissue. Biology of these primary tissues may carcinoma: global mRNA classification versus tumour- Have an after-work beer with us differ significantly from metastatic tissue, especially cell phenotype classification. J Pathol, 2017. 242(1): at our booth D58 and discover 11 following an antineoplastic therapy . Accordingly, p. 113-125. our Clearly Defined Urology Solutions. response prediction in primary tissues may not be 4. Seiler, R., et al., Impact of Molecular Subtypes in related to actual response of metastases. Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy. Eur Urol, First come, first served. Future precision oncology approaches are likely to 2017. 72(4): p. 544-554. On Saturday and Sunday as of 17.00! focus first on perioperative therapy before 5. Advanced Bladder Cancer Overview, C., Neoadjuvant according options in the metastatic setting may chemotherapy for invasive bladder cancer. Cochrane become tangible. Database Syst Rev, 2005(2): p. CD005246. 6. Leow, J.J., et al., A systematic review and meta-analysis In this context, prognostic biomarkers may help to of adjuvant and neoadjuvant chemotherapy for upper identify patients unlikely to benefit from tract urothelial carcinoma. Eur Urol, 2014. 66(3): p. Hitachi Medical Systems Europe Holding AG perioperative systemic therapy, as well as patients 529-41. www.hitachi-medical-systems.eu most likely to benefit. Examples for prognostic 7. Gupta, S. and A. Mahipal, Role of systemic chemotherapy

Saturday, 17 March 2018 EUT Congress News 9 Today’s European Urology Events

How to write the introduction and methods 1. Welcome Jim Catto, Sheffield (GB) ESU Writing Course Aims and objectives: 2. How to write an introduction Understand how to construct a well written Giacomo Novara, Padova (IT) Part 1 introduction and methods section for your 3. Group working I manuscript. Learn how to work through 4. How to write the methods section examples of good and bad practices, and Christian Gratzke, Munich (DE) understand key points when writing. Obtain 5. Key features for a systematic review insight from editors on what they expect Marcus Cumberbatch, Sheffield (GB) to see. 6. What to look for in the statistics section Christian Gratzke, Munich (DE) • To understand what makes a 7. Group working II th good introduction 8. Questions and answers March 17 • To understand what makes a good methods section 8.30 – 10.30 • To understand about systematic reviews Orange Area, Room 1 (Level 0) and meta-analysis • To learn from experienced editors

How to write results and discussion 1. Welcome Jim Catto, Sheffield (GB) ESU Writing Course Aims and objectives: 2. How to write the results chapter Learn the best way to draft the results and Stephen Boorjian, Rochester (US) Part 2 discussion section of a scientific paper. 3. Choosing and presenting your Understand how to work through examples statistical analyses of good and bad practices, to find the key Melissa Assel, New York (US) points of the manuscript. Obtain insight 4. Group working I from editors on what they expect to see. 5. Writing the discussion section Jean-Nicolas Cornu, Rouen (FR) • To understand what makes a good results 6. What the editor looks at when reviewing section and how to best present your data the results and discussion th • To understand what makes a Stephen Boorjian, Rochester (US) March 17 good discussion 7. Group working II • To learn from experienced editors 8. Questions and answers 12:00 – 14:00 Orange Area, Room 1 (Level 0)

We would like to invite you to attend the Platinum Hour drinks reception to meet and greet the editors, authors and reviewers of the European Urology Platinum hour family of three: European Urology, European Urology Focus and European Urology Oncology. Please join us to toast to the family’s new sister journal European Urology Oncology.

This new journal complements the family by delivering high quality research while pursuing the goal of a multi-disciplinary approach. Urology, Medical Oncology, Radiation Therapy, Imaging, Pathology and Basic Research working together with the same final aim: to improve patient care. If you’ve got practice changing, groundbreaking research in urological oncology, you th th can directly submit your original article via this link: ees.elsevier.com/euonco. March 17 - 18 We look forward to answer any questions about the new journal, or 16.00 – 18.00 another member of the European Urology family, during the drinks reception European Urology booth #C3-C29 at our booth!

europeanurology.com eufocus.europeanurology.com europeanurology.com/euoncology

10 EUT Congress News Saturday, 17 March 2018 Infectious complications and fURS fURS procedure may lead to severe infective complications if crucial measures are not properly taken

Prof. Kemal Sarica operative urine culture prior to procedure however Chairman has not been found to guarantee the absence of EAU Section of post-operative infection. Urolithiasis ( EULIS) Chief, Dept.of Urology fURS procedure could be associated with higher risk Medical School of post-operative infection in cases with infected Kafkas University stones, longer operative times, and the presence of Kars (TR) residual fragments as well as foreign bodies (10).On the other hand, again higher intrapelvic pressure levels during fURS procedure could be associated with post-operative sepsis and Zhong et al demonstrated that the patients who had sustained Surgical management of renal stones has an intrapelvic pressure ≥30 mmHg were more likely substantially changed in the last two decades to develop post-operative fever11. where endourological procedures, such as percutaneous nephrolithotomy (PCNL) and flexible However, although the UAS reduces the renal pelvic uretero(reno)scopy (fURS) became the standard pressure and may help to reduce the intra-operative treatment options for the minimal invasive removal absorption of lavage fluid, the authors did not find of renal stones. any increased risk of infective complications when it was not used (p = 0.43). In the same direction, Related with this issue, increasing experience several reports have not found any association gained in the ureteroscopic management of upper between intrapelvic pressures and the incidence of urinary tract calculi as well as the marked post-operative fever after PCNL12. improvements in the instrument technology have increased the popularity of fURS as a safe and Regarding the other possible risk factors for acceptable treatment alternative for small-to- infectious problems after fURS, in their original moderate-sized renal stones up to 20 mm1. study Martov et al.13 have reported that the patients with such infective complications had significant Published data on this aspect so far has clearly comorbidities (coronary heart disease, CKD, demonstrated that fURS in experienced hands may alteration of lipid metabolism, anticoagulant Surgeons should be aware of potential serious infectious complications arising from fURS procedures and the corresponding reveal potentially higher stone-free rates (SFR) than therapy) at univariate analysis. An increased risk of management strategies. extracorporeal shock wave lithotripsy (ESWL) and infectious complications following FURS was found lower morbidity than PCNL in the treatment of such to be associated with some comorbidities like stones. Morover, flexible uretero(reno)scopic laser Crohn’s, cardiovascular disease, high ASA score and higher complication rates, including post-operative 6. Rao PN, Dube DA, Weightman NC et al (1991) Prediction disintegration and successful removal of these high stone burden. high fever and sepsis, than URS without pre- of septicemia following endourological manipulation stones with high SFR did reduce the morbidity and operative sepsis19. for stones in the upper urinary tract. J Urol 146:955. hospital stay to a certain extent in the majority of Thus, the increased risk of infectious complications 7. O’Keeffe NK, Mortimer AJ, Sambrook PA, Rao PN (1993) the cases. among cases with greater comorbidities emphasizes Infective complications Severe sepsis following percutaneous or endoscopic the importance of judicious patient selection for this In the light of the facts mentioned above and procedures for urinary tract stones. Br J Urol 72:277–283 However, despite its minimal invasive and efficient type of procedure. Additionally, Fan et al. found that despite its minimal invasive nature and successful 8. Geavlete P, Georgescu D, Niţa ̆ G, Mirciulescu V, Cauni V natüre, fURS procedure is not completely pyuria, operative duration, and infectious stones outcomes, fURS procedure may results in severe (2006) Complications of 2735 retrograde semirigid complication-free and some certain problems could were independently related to infectious infective complications if necessary measures are ureteroscopy procedures: a single-center experience. J be encountered either during and/or early complications14. not taken well among which the proper selection of Endourol 20:179–185 post-operative follow-up period. Such problems the cases is of utmost importance. 9. Troxel SA, Low RK (2002) Renal intrapelvic pressure could be partly explained with the rapid expansion On the other hand, and equally important, during percutaneous nephrolithotomy and its of URS indications to larger and more complicated intraoperative stone culture has been found to be correlation with the development of postoperative stones and to elderly patients with significant more reliable than a pre-operative urine culture in “...intraoperative stone culture has fever. J Urol 168:1348–1351 comorbidities originating from such a high success guiding both the antibiotic therapy in patients who been found to be more reliable 10. Sohn DW, Kim SW, Hong CG, Yoon BI, Ha US, Cho YH rate and low complication rates obtained. develop sepsis and also identifying patients at risk (2013) Risk factors of infectious complication after for post-operative sepsis. These results have clearly than a pre-operative urine culture ureteroscopic procedures of the upper urinary tract. J Relevant studies indicated well that inappropriate outlined the importance of obtaining an intra- in guiding both the antibiotic Infect Chemother 19:1102–1108 widening of the indications might result in a higher operative stone culture in a routinely performed 11. Zhong W, Zeng G, Wu K, Li X, Chen W, Yang H (2008) incidence of severe complications, including febrile manner. therapy in patients who develop Does a smaller tract in percutaneous nephrolithotomy urinary tract infection (UTI), need for blood sepsis...” contribute to high renal pelvic pressure and transfusion, renal dysfunction or septic shock. Studies have shown that 8% of the patients with postoperative fever. J Urol 22:2147–2151 positive stone cultures developed sepsis and this 12. Troxel SA, Low RK (2002) Renal intrapelvic pressure Related with this issue, by using the Clinical value was significantly greater than the percentage Surgeons have to be aware of the possibility of during percutaneous nephrolithotomy and its Research Office of the Endourological Society with negative stone cultures who developed sepsis serious infectious complications and their correlation with the development of postoperative (CROES) database in their original study, De la (1 %). As a result, data from the stone culture were management strategies. It is obvious that urine fever. J Urol 168:1348–1351 Rostte et al., analyzed 11,885 patients treated with found to be critical in determining the proper culture findings should be obtained in all patients 13. Alexey Martov, Stavros Gravas, Masoud Etemadian et al URS (consisted of data from 114 centers in 32 treatment in these patients and more importantly, before the procedure and an infection-free urine (2015) Postoperative infection rates in patients with a countries) and reported the stone-free as well as the stone culture seemed to have a higher noted after an appropriate antibiotic management negative baseline urine culture undergoing post-operative complications rates to be 85.6 % and association with post-operative sepsis than did the will certainly limit the risk of infectious ureteroscopic stone removal: a matched case-control 3.5 % respectively2. pre-operative urine culture (15,16). complications to a considerable extent after fURS. analysis on antibiotic prophylaxis from the CROES URS global study. J Endourol 29:171–180 The most frequent complication noted was fever (2.8 Additionally, published data do indicate that the 14. Fan S, Gong B, Zet Hao et al (2015) Risk factors of %) in that study. Of the complications noted so far “...despite its minimal invasive proper and careful use of an appropraitely sized infectious complications following flexible ureteroscope after fURS, while infection affecting up to 1.8 % of nature and successful outcomes, ureteral access sheath during the procedure may with a holmium laser: a retrospective study. Int J Clin patients undergoing flexible uretero(reno)scopy and allow a successful and, more importantly, infection- Exp Med 8(7):11252 laser lithotripsy has been reported1.More recently, fURS procedure may results in free procedure. 15. Wollin DA, Joyce AD, Gupta M, Wong MYC, Laguna P, Fan showed in a retrospective study that the severe infective complications if Gravas S, Gutierrez J, Cormio L, Wang K, Preminger incidence of infectious complications after fURS may In summary, culture antibiogram-based appropriate GM1. : Antibiotic use and the prevention and range between 1.7 and 18.8 %3. necessary measures are not taken antibiotic administration, lower irrigation pressure management of infectious complications in stone well...” during the procedure along with an unobstructed disease. World J Urol. 2017 Sep;35(9):1369-1379. Several subsequent studies have also reported that peri-operative urinary drainage, obtaining 16. Motamedinia P, Korets R, Badalato G, Gupta M.: urosepsis can be a majör problem for management intra-operative urine or stone culture are the Perioperative cultures and the role of antibiotics during despite the use of appropriate antibiotics prior to Last but not least, sepsis after URS is a major established important factors in effectively stone surgery. Transl Androl Urol. 2014 Sep;3(3):297- the endourological procedures4-6. complication which should inevitably be avoided. preventing post-operative infectious complications, 301. However, only a few studies clearly described the including sepsis. 17. Eswara JR, Shariftabrizi A, Sacco D (2013) Positive stone As previously mentioned, infective complications incidence of sepsis after URS or endourological culture is associated with a higher rate of sepsis after following fURS remain a decisive issue and it has procedures. Geavlete reported that the incidence of References endourological procedures. Urolithiasis 41:411–414 been reported that this procedure may still have fever and sepsis was 1.13 % among 2,735 cases 1. Knopf HJ, Graff HJ, Schulze H (2003) Perioperative 18. Sohn DW, Kim SW, Hong CG, Yoon BI, Ha US, Cho YH unforeseen post-operative systemic and sometimes treated with semi-rigid URS at a single center8. antibiotic prophylaxis in ureteroscopic stone removal. (2013) Risk factors of infectious complication after life-threatening infection despite a well-performed Eswara et al. reported that the incidence of sepsis Eur Urol 44:115 ureteroscopic procedures of the upper urinary tract. J appropriate pre-operative antibiotic therapy along was 3.0 % (11/328) after endourological procedures, 2. de la Rosette J, Denstedt J, Geavlete P et al (2014) The Infect Chemother 19:1102–1108 with the use of ureteral access sheath (UAS) which including 54 cases of percutaneous clinical research office of the endourological society 19. Youssef RF, Neisius A, Goldsmith ZG et al (2014) Clinical effectively reduces the likelihood of pyelolymphatic nephrolithotomy17. ureteroscopy global study: indications, complications, outcomes after ureteroscopic lithotripsy in patients or pyelovenous backflow7. Access sheaths also allow and outcomes in 11,885 patients. J Endourol 28:131–139. who initially presented with urosepsis: matched pair for continuous irrigation of the renal pelvis and Finally,Youssef et al. reported sepsis developed 3. Fan S, Gong B, Zet Hao et al (2015) Risk factors of comparison with elective ureteroscopy. J Endourol improved stone clearance, as well as lower renal post-operatively in two patients (1.4 %) with diabetes infectious complications following flexible ureteroscope 28:1439–1443 pelvic pressures that may be protective against (one with and one without previous sepsis), and with a holmium laser: a retrospective study. Int J Clin pyelovenous and pyelolymphatic backflow8,9. post-operative fever developed in five patients with Exp Med 8(7):11252 . Saturday 17 March previous sepsis. Regarding the possible risk factors, 4. Lee WJ, Smith AD, Cubelli V et al (1987) Complications 10.15-14.30: Meeting of the EAU Section of Regarding the risk of infective complications after a while Sohn and colleagues reported that bacteriuria of percutaneous nephrolithotomy. AJR Am J Roentgenol Urolithiasis (EULIS), Management of stones: successful fURS, while it is highly crucial to postpone and catheterization were the strongest risk factors for 148:177. Advancing technology, increasing experience and the treatment of stones in the presence of an urinary severe febrile complications18, Youssef et al. 5. Michel MS, Trojan L, Rassweiler JJ (2007) Complications changing concepts. Where are we in 2018? tract infection, a well-confirmed negative pre- demonstrated that URS with pre-operative sepsis had in percutaneous nephrolithotomy. Eur Urol 51:899.

Saturday, 17 March 2018 EUT Congress News 11 Ernest Desnos: Honouring urology historians Historical Exhibition features artefacts from Desnos’ career and much more

By Loek Keizer from the early 20th century on which the EAU Ernest Desnos Prize is based. Last night saw the presentation of the first EAU Ernest Desnos Prize for contributions to the field of the In honour of our host country this year, the exhibition history of urology. The EAU History Office also features several highlights from the history of unanimously voted to honour Prof. Sergio Musitelli urology in Denmark and the Scandinavian countries. It (IT), long-term expert of the Office and (co)-author of is completed with items related to the First World several unique volumes dedicated to the earliest War, the end of which was one century ago this year. history of urological procedures. The First World War disrupted the development of urology, and particularly the international cooperation Musitelli, who turned 90 this year, was Visiting within the field just as it was reaching maturity. Professor of the History of Urology, Sexology and Several prominent British urologists were veterans of Andrology at the University of Pavia for many years, the Great War, and the exhibition explores their time following a long career in philosophy, ancient arts, of service and subsequent accomplishments in oriental literature and languages and the history of urology. ancient science and medicine. New publications Since the start of the EAU History Office, Mustelli A good opportunity to visit the Historical Exhibition functions as a professional history expert and Prof. Sergio Musitelli, recipient of the first EAU Ernest Desnos would be when you collect your copies of the latest participates in all activities. Based on his position as Prize EAU publications. EAU members can collect their an expert in history, he was one of the most active copy of the 25th Anniversary Edition of De Historia contributors to the work of the EAU History Office, Urologiae Europaeae, the congress gift For this Relief, not only with numerous articles and books but also accomplishments are co-founding the AFU and later Much Thanks! by Dr. Johan Mattelaer, as well as other in reviewing submitted articles for the annual De the SIU, as well as treating Emperor Napoleon III for a membership benefits, depending on your Historia Urologiae Europaeae volumes. Furthermore, bladder stone in 1873 and major pioneering work on entitlements. The original Desnos medal from the early 20th century on he was responsible for a detailed and reliable index prostate brachytherapy. which the EAU Ernest Desnos Prize medal is based of all published volumes of these series. Mattelaer’s latest publication explores the depiction However his most significant contribution was in the of urination in art, both classical and contemporary. It In the words of EAU History Office Chairman Prof. field of the History of Urology. Therefore his ‘magnum is a beautifully illustrated coffee table book that The 25th Anniversary Edition of De Historia features Philip Van Kerrebroeck (BE): “Sergio’s own opus’ is the first book on the History of Urology ever. celebrates our field and offers unique insights. contributions from past editors, special attention for publications bring in an original viewpoint, always This book was published in 1914 as “Histoire de the inaugural Ernest Desnos Prize winner, as well as based on extensive literature search, but with a very l’Urologie” (History of Urology, Paris. Doin éditeur, the usual wide-ranging articles that cover the history critical interpretation of the available material. He 1914). The large volume presents, in 294 pages with of urology. teaches us all that history, and hence also history of 196 beautiful black and white illustrations and nine urology is much more than telling an interesting story, coloured reproductions, a complete overview on the but that it is also a science. Hence he was responsible History of Urological Surgery and Urology from its The Historical Exhibition is located across the for a further professionalization of historiography in origins to the beginning of the 20th century. EAU Booth (H69). Publications can be collected the field of urology, and we all profit from his efforts.” at the EAU Booth. The EAU Booth is open on Historical Exhibition the following days: The prize bears the name of Dr. Ernest Desnos This year’s Historical Exhibition, which is to open at (1852-1925), as a tribute to this pioneering French the EAU Booth in the Exhibition Hall this morning Saturday 17 March, 09:30-18:15 urologist who was also an eminent urology historian features several items from Desnos’ impressive Sunday 18 March, 09:30-18:15 and who wrote the first book devoted solely to the oeuvre. His most notable historical works, some Desnos’ Histoire de l’Urologie (1914), considered to be the first Monday 19 March, 09:30-15:30 history of urology. Not least of Desnos’ personal artefacts, and the original Desnos medal single volume publication on the history of urology

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12 EUT Congress News Saturday, 17 March 2018 EAU Guidelines: Ensuring consistent European urological care Variations in practice exist despite high-quality standards

Prof. Dr. James Reasons for variation in practice and non-adherence Guideline developers need to ensure that guidelines N’Dow to guidelines have a clear structure and local applicability in order Chairman, EAU Guidelines are ideally informed by systematic reviews for guidelines to be useful in different settings and Guidelines Office of the evidence and those systematic reviews are in healthcare systems. Although guidelines have the Dept. of Urology turn informed by primary research of treatment potential to improve care by promoting effective University of effectiveness. A major hurdle for conducting interventions and discouraging ineffective ones, Aberdeen systematic reviews occurs when outcomes are not publication of guidance alone is unlikely to optimise Aberdeen (GB) defined, measured and reported in the same way and practice. Development of guidelines must be at the same time point across the included studies. supported by an effective dissemination and This heterogeneity means that synthesising and implementation strategy. The EAU have successfully creating meaningful and impactful evidence developed an effective mass dissemination platform summaries is often difficult in urology. For guideline through Twitter. The EAU Twitter platform has also Adherence to national and international guidelines is panels, it is difficult to make strong recommendations been used to estimate adherence to EAU guidelines sub-optimal throughout Europe. In fact, significant for or against treatment interventions in the most recommendations. The EAU Guidelines Office gaps currently exists in terms of the application and transparent way because they must rely on sub- ‘IMAGINE’ project (IMpact Assessment of Guidelines use in clinical practice of the EAU Guidelines, even optimal summaries of the evidence. Implementation and Education) has been developed though they are based on standardised high-quality to effectively tackle the issues of non-adherence and methodology and are endorsed by all 28 European Another limitation in relation to guidelines implementation with the ultimate goal of ensuring all Member States. development is that guideline panels are often limited patients across Europe receive the best evidence- to those with clinical and methodological expertise. based standardised care. For example, we are aware that in some countries, The voice of the other stakeholder groups in the approximately one out of four men with prostate design and delivery of healthcare (e.g. patients, Why should we improve clinical practice guidelines cancer received androgen deprivation therapy despite carers, charitable organisations and industry) is often adherence? the fact it is not recommended by the EAU Guidelines. missing from these discussions. Given the emphasis If evidence-based best practice recommendations are Cover of the new 2018 EAU Guidelines edition This in turn increases the risk of short- and long-term on patient-focused outcomes and the need for not disseminated effectively and knowledge is not side effects in these patients, and the costs related to guidelines to be responsive to stakeholder needs, actively transferred, variations in practice are likely to disease management. strong arguments exist for the inclusion of all of the occur. Where variations in practice occur, healthcare is harmonisation across all EU member states. It is key stakeholder groups in the guidelines development unequal within nation states and across European fundamentally important that such guidelines have a In addition, studies have reported that despite clear process. Achieving true stakeholder engagement in member states, whilst health systems are most likely high degree of visibility, uptake and adherence by EAU guideline recommendations advocating the use the Guidelines development, delivery and inefficient. Furthermore, if all stakeholders, including clinicians and healthcare providers. of intravesical chemotherapy post-surgical resection implementation process will: patients, are not meaningfully included in in non-muscle invasive bladder cancer, adherence to consultations to prioritise research areas, to Whilst the EAU guidelines are now endorsed by all EU these guidelines is low and varies widely, with • Guarantee that all stakeholders have confidence determine which outcomes are the most important, member states, European Union/European estimates ranging from 22% to 71% in a sample of in the guidelines development process and as and to ensure recommendations are phrased Commission endorsement would undoubtedly five European Union countries. such the resulting recommendations; appropriately, then they are denied informed increase the recognition of the importance of shared-decision making. guidelines in general, as well as their visibility, There are also similar concerns regarding • Ensure that the recommendations are dissemination and implementation. If this integrated non-adherence to non-oncological guidelines in appropriate, achievable and can be translated There is an urgent need to harmonise clinical practice model for the development, dissemination and urology. A study conducted to assess adherence into corresponding health behaviour leading to throughout Europe and guidelines are the ideal implementation of European-wide guidelines for levels to the Guidelines on Urinary Incontinence better treatment compliance and better health framework for doing so. The key to this is to ensure urology could be achieved, the potential for other of the Dutch College of General Practitioners outcomes; and the availability of high-quality European-wide clinical areas to apply this cohesive model would be found that approximately only a third of surveyed guidelines, which are robustly established, fit for promising with the prospective overwhelmingly clinicians complied with treatment • Result in recommendations and guidelines which purpose and comprehensive. The EAU guidelines are positive impact on harmonisation and a far more recommendations. facilitate person-centred care. an excellent demonstrator model for achieving effective healthcare provision in Europe. URO 84 2.0 02/2018/A-E

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Saturday, 17 March 2018 EUT Congress News 13 Update in vaginoplasty technique Prospective randomized studies needed to identify ‘ideal’ vaginopasty

Prof. Ervin Kocjancic Regarding nontransgender vaginoplasty; the Frank University of Illinois method, which was described in 1938, involves the Dept. of Urology utility of graduated vaginal dilators to create a vagina Chicago (USA) or augment an existing structure inadequate for sexual intercourse (Davies et al., Ismail Pratt et al.). The “semisurgical” Vechietti procedure, which requires elasticity of the vaginal skin, allows creation of neovagina by passive traction rather than dilation. Herein an acrylic “olive” with attached tension threads is placed at the vaginal dimple and the threads are passed under laparoscopic control from the vaginal dimple to a traction device on the abdominal wall Co-Author: Ömer Acar, Istanbul (TR) (Davies et al.). The Davydov technique, which may also be performed laparoscopically and is more suitable for Gender dysphoria (GD) can be described as a those patients with perineal scarring and/or vaginal discrepancy between the gender assigned at birth inelasticity, includes liberation of peritoneum from the and gender identity (Bizic et al.). Patients with GD pelvic side walls and the Pouch of Douglas. Neovagina exhibit strong cross-gender identification, persistent is created by suturing a vaginal “roof” of peritoneum discomfort with their anatomical sex and a sense of and then filled with a soft mould which remains in inappropriateness in the gender role of that sex place for one week (Davies et al., Ismail I et al.). which lead to distress and bother in social, Intestinal vaginoplasty, which will be discussed in occupational, and other important areas of more detail as related to transgender vaginoplasty, can functioning (Horbach et al.). also be applied for non-transgender patients.

Recent studies have shown that the prevalence of In transgender vaginoplasty, surgical techniques can be trans females and trans males to be 1:12,900 and divided into three main categories according to the 1:33,800, respectively. Individuals with GD are nature and origin of the tissue(s) used for Figuur 2: Disasembeling of the penis and preparation of the neo clitoris becoming increasingly more accepted in society reconstruction: Skin grafts; Penile-scrotal skin flaps (Colebunders et al., De Cuypere et al.) and therefore (Penile skin inversion technique); and pedicled small the number of patients who feel confident enough to or large bowel segments (Intestinal vaginoplasty) bearing surface, sensate nature, thin connective tissue formation between the rectum and neovagina. The seek gender reassignment surgery has increased and relatively minimal tendency to contract represent overall incidence of rectovaginal fistula was reported to substantially (Dhejne et al.). The main goals of vaginoplasty are to achieve an the main advantages of using penile skin-based flaps be 1% (Bouman et al.). In such an event, surgical esthetically and functionally ideal perineogenital (Bizic et al.). In cases where the penile skin is deficient correction can be done via double-layer of vascularized The treatment of patients with GD requires a complex that will satisfy the patient (Bizic et al., Karim (circumcision, micropenis etc.), several technical tissue +/- temporary colostomy. Being aware of this multidisciplinary approach which consists of et al.). The neovagina should be moist, elastic and refinements can be applied such as combining the possibility, prompt intraoperative recognition, psychiatric and psychologic evaluation, cross-sex hairless with a depth of at least 10 cm and a diameter penile skin flap with scrotal (Bizic et al., Selvaggi et al.) appropriate surgical correction, preoperative bowel hormonal therapy and reconstructive surgical of 3-4 cm. The clitoris should be small, obscured and and/or urethral flaps (Bizic et al., Perovic et al.). preparation and perioperative antibiotic prophylaxis procedures aiming to modify the body image and sensitive enough to enable complete arousal. Labia Utilizing a perineal flap together with a scrotal graft in will help to minimize the potential problems function toward the desired gender (Bizic et al.). The minora and majora should resemble the female vulva addition to penile skin may also serve well to lengthen associated with rectal injury. World Professional Association of Transgender Health as much as possible. Innervation of the new genitalia the neovaginal cavity (Kocjancic et al.). (WPATH) has established the standards of care for the complex should be functionally intact in order to offer Labiaplasty and clitoroplasty are integral parts of a multidisciplinary treatment of such individuals. Before a satisfactory level of erogenous stimulation during Van Noort et al. combined penile skin with a scrotal full vaginoplasty procedure. Usually the scrotal skin and the undergoing genital reconstruction; transgender sexual intercourse (Bizic et al., Karim et al., Selvaggi et thickness skin graft and/or a posteriorly based scrotal base of the penile skin is used to create labia majora patients are required to provide two recommendation al.). Transwomen who prefer an esthetic outcome skin flap. The major drawback of this modification and miora, respectively. Adipose tissue around the letters from two independent, certified pyschiatrists without a functional vagina can undergo a vulvoplasty would be the introduction of hair-bearing scrotal skin spermatic cord can additionally be used for labiaplasty. and a letter of confirmation documenting their without vaginoplasty. within the posterior lining of the vagina if hair removal Spatulated distal urethra can be used to create the floor compliance with the hormonal therapy arranged by has not been done peroperatively. To avoid this, of the vestibulum. Clitoris is constructed with the dorsal the endocrinologist for a period of at least one year 1. Skin grafts permanent epilation can be accomplished before portion of the glans penis in a horseshoe or W-pattern (wpath.org). Local nongenital skin flaps, full-thickness skin grafts vaginoplasty via laser therapy or electrolysis in patients (Colebunders et al., Perovic et al.). It is of utmost (FTG) or split-thickness skin grafts (STG) have been with a limited amount of penile skin. Alternatively, the importance to preserve the dorsal neurovascular The core surgical interventions that are applied used for neovagina formation. Hage and Karim graft can be meticulosly cleared off adipose tissue and pedicle to enable the neoclitoris react to sexual within the context of trans women are; facial harvested FTG from the lower abdomen and a used a hair follicles immediately after harvest at the stimulus. Additionally, the labia majora and minora feminizing surgery, voice surgery and mold to insert it in the neovaginal cavity. They backbench. Perovic and Djordevic has described should be sutured to the de-epithelialized area of the chondrolaryngoplasty, breast augmentation, and mentioned no postoperative complications after a another technique in which a spatulated urethral flap neoclitoris so that the neoclitoris looks conical and orchiectomy, penectomy and vaginoplasty. follow-up duration of seven months. All of their was fixed onto the penile skin flap to increase hidden. This type of clitoroplasty provides good Vaginoplasty, which is the last step of the transition patients (n= 6) were reported to be “subjectively” neovaginal length and width. This addition also served sensitivity and sexual satisfaction for the patients (Bizic process, depicts the construction of a vagina that pleased with the cosmetic and functional outcome. well for the vaginal moisture and lubrication given the et al., Selvaggi et al.). Although flaps contract much less resembles a biological vagina in form and function. Mean neovaginal depth and width was 12 and 3 cm, well vascularized nature of the urethral flap. often than grafts, patients are still required to use a This procedure includes orchiectomy (can be respectively (Horbach et al., Hage et al.). dilator postoperatively for at least one year to prevent performed as a first stage procedure before vaginal Buncamper et al. used additional full-thickness skin neovaginal and introital stenosis. reconstruction), amputation of the penis, creation Siemssen and Matzen used FTG of penile skin, STG or a graft in the penile inversion vaginoplasties of and lining of the neovaginal cavity, reconstruction of combination of both in a group of 11 patients. They did transgender women who have a penile skin length of 3. Pedicled small or large bowel segments (intestinal the urethral meatus and construction of the labia and not report on neovaginal dimensions, patient less than 12cm in an effort to obtain more vaginal vaginoplasty) clitoris. Vaginoplasty can also be applied to biological satisfaction and quality of life outcomes. Overall, depth and create an esthetically superior vulva. In their Intestinal vaginoplasty has become a valid option that women with disorders of sexual development (such vaginal stenosis was the most frequently (45%) case-control study (n= 100, 32 with and 68 without can be used for constructing a neovagina. Especially in as Mayer-Rokitansky-Kuster-Hauser (MRKH) encountered complication and it was noted in all (three additional FTG), none of the tested parameters cases where no redundant penile and/or scrotal skin is syndrome) and those who underwent vaginectomy out of three) of the patients who were reconstructed by (patient-reported esthetic outcome, overall satisfaction available for grafting, intestinal grafts provide a good due to gynecological malignancy or trauma. STG alone with the neovagina, sexual function and genital image) alternative. Some authors used 7 cm as the cut-off for differed significantly between the two groups. Recently, penile skin length below which bowel-based options Vaginoplasty techniques 2. Penile skin inversion technique Papadopulos et al. assessed the surgical outcome of should be offered (Buncamper et al.) A lack of penile Different nonsurgical and surgical techniques have Penile skin inversion technique remains the method of their combined vaginoplasty technique in which and scrotal skin is often present in transwomen who been developed and utilized for the purpose to choice for vaginoplasty in MTF transition. Its origin spatulated urethra together with a scrotal skin graft started hormonal therapy (puberty blockers) at a reconstruct a normal functioning vagina with a dates back to 1957, when Gillies and Millard reported was used in addition to the penile skin flap to form the younger age. Pedicled bowel segments can also be satisfactory sexual function and appearance for these on the use of penile skin as a pedicled flap for the neovagina. The main aim of this procedure was to used when prior neovaginal reconstructive attempts patients. vaginal lining. Later on, Burou popularized the utility achieve the largest possible vaginal depth and width, with skin flaps and/or grafts failed in transgender of anteriorly pedicled increasing the lubrication level of the neovagina and patients. The need to elongate the vagina in penile skin flaps for the providing a more esthetic mons pubis by decreasing transwomen requiring greater depth after a previous inversion technique. the abdominal tension that might be more pronounced neovaginal construction is another indication to Currently, penile skin where solely penile skin was used for reconstruction. proceed with intestinal vaginoplasty. inversion technique is the They also created a “clitoral hood” with an esthetic most frequently prepuce by dividing the foreskin into an inner and Use of pedicled bowel segments offers some performed and hence the outer layer in an effort to prevent clitoral advantages regarding cosmesis and sexual function. most extensively studied desensitization. Measured postoperative neovaginal First of all, it provides sufficient amount of tissue for surgical procedure within depth ranged from 11,77 to 14,99 cm, depending on the optimal vaginal depth and width. Moreover, this tissue the context of MTF gender size of the dilator used (25-40 mm). All of the patients is self-lubricating given the secretory potential of the reassignment. Herein; the further reported intact and favorable vaginal, clitoral intestinal mucosa. Additionally, intestinal inner lining inverted penile skin on an and labial sensitivities. resembles the vaginal mucosa in texture and abdominal or more appearance. Lastly, the lumen of the isolated intestinal inferior pedicle is used as Denonvillier’s fascia should be opened to create a segment has little tendency to shrink which eliminates an outside-in skin tube space for the neovagina. Dissection should be carried the need for lifelong postoperative vaginal dilatation for the lining of the out up to the level of pouch of Douglas superiorly and which is almost always necessary in non-intestinal neovagina (Bizic et al., ischial spines laterally. This type of extended dissection graft/flap based neovaginal constructions (Bouman et Horbach et al.). of the rectoprostatic space allows for omission of al., DeMarco et al.). Intestinal vaginoplasty has also sacrospinal fixation, thus preventing damage to the some inherent disadvantages such as; the need for Preserved vascularization pudendal neurovascular bundle (Kocjancic et al.). intestinal anastomosis, the risk of postoperative of the penile skin, its Inadvertent rectal injuries can occur during the Figuur 1: Penile skin inversion mobility, non-hair- development of this space and may lead to fistula Continued on page 15

14 EUT Congress News Saturday, 17 March 2018 Managing complex cases in functional urology How many drugs my BPH/BPE patients may need to control LUTS?

Dr. Frank Van der Aa For current medical LUTS treatment, one can choose LUTS due to BPH are a Functional and between several medications. When considering combined symptom Reconstructive medical LUTS treatment, one should take into account complex, often presenting Urology the risk of progression of the underlying BPH, the with voiding and with Neurourology invalidating nature of the symptom complex, the storage symptoms, with Department of predominant symptom(s), the risk of side effects and day- and nighttime Urology the cost of the treatment2. symptoms and there is a UZ Leuven known association with Leuven (BE) Prior to considering treatment, it is evident that erectile dysfunction. When symptoms should be bothersome for the patient. patients present with a Patients with light to moderate symptoms should be combination of these reassured and given lifestyle advice3. symptoms, it is a normal Male lower urinary tract symptoms (LUTS) are an reflex to prescribe increasingly frequent encountered symptom complex. The risk of progression is easily defined as increasing medications that treat the Due to the increased life expectancy and the high LUTS (for the majority of patients). In a subset of different aspects of the quality of life, people seek improvement or cure for patients, acute urinary retention (AUR) and need/ symptom complex. A LUTS. demand for surgical treatment define progression. second reason is to have a Patients who are at risk for progression, might benefit faster and stronger The majority of male LUTS is still caused by benign from hormonal treatment with 5 alpha-reductase response by combining prostatic hyperplasia (BPH). Mostly, but not always inhibitors since this treatment has a well proven risk different working BPH is associated with benign prostatic enlargement reduction for surgery and AUR. Certainly when mechanism to treat (BPE). When patients seek help for invalidating LUTS comorbidities put the patient at risk for surgical BPH-related LUTS. due to BPH, the treating clinician should elucidate treatment, this treatment should be offered. Easily certain elements in order to select the right treatment detectable risk factors for progression are patient age, An example is the direct for the right patient. prostate volume, PSA level and presence of PVR4. relaxing effect on smooth muscle from alpha- Firstly, the clinician should confirm that the patient Voiding symptoms blocking agents combined is suffering from uncomplicated BPH related LUTS. The nature of the symptom complex will determine with the slow but The functional lower urinary tract disorder should the medical treatment. The majority of patients will sustained effect on not be associated with complications of the lower have voiding symptoms as part of male LUTS. Voiding prostate stroma and gland urinary tract (such as high PVR, bladder stones, symptoms in the presence of a small prostate will tissue of 5-alpha-reductase bladder diverticula, recurrent bleeding and direct the clinician to the use of alpha-blocking agents inhibitors. Another recurrent infections) or complications of the upper or phosphodiesterase-5 inhibitors. The presence of example is the combination urinary tract (such as hydro-ureteronephrosis, renal storage symptoms will direct the clinician to treatment of alpha-blocking agents function deterioration or ascending urinary tract with antimuscarinic agents or beta-3-adrenoreceptor with antimuscarinics to Most male LUTS is caused by benign prostatic hyperplasia (BPH) which, in turn, is linked to infections). These cases mandate (surgical) agonists. Depending on the size of the prostate, also treat both prostate/bladder benign prostatic enlargement (Photo: Getty Images) treatment. hormonal therapy with 5-alpha-reductase inhibitors neck and detrusor muscle can be considered. In the case of bothersome in patients with In the case of uncomplicated BPH-related LUTS, nocturia, desmopressin could be an option. predominant storage LUTS. Both above mentioned combinations are also patients generally prefer medical treatment over recommended by the EAU guidelines. After surgical treatment. In the last decades, the incidence There are several reasons to combine different agents Unfortunately, there are also downsides on monotherapy, these combinations are the most of surgical treatment for BPH-related LUTS has of the above-mentioned treatment options in one combination therapy. First of all, the combination of frequently prescribed medications12. significantly declined. The incidence of medical patient. A first reason is to tackle the different aspects several active components not only increases efficacy treatment however has increased significantly1. of the symptom complex. but also comes with an increased rate and spectrum There is limited but promising evidence for some of side effects. Secondly, taking more than one pill a other dual combinations, such as alpha-blocking day increases the likelihood of intake errors and of agents with phosphodiesterase-5 inhibitors and adherence problems. Fixed dose combinations, phosphodiesterase-5 inhibitors with 5-alpha- Update in vaginoplasty... Continued from page 14 derived vaginoplasties, respectively). Introital combining two active ingredients in one tablet reductase inhibitors13,14. stenosis, necessitating revision surgery, was the diminish these problem5. In some healthcare settings, bowel-related complications (ileus, anastomosis leak, main postoperative complication and this was seen the price of combination therapy might be high for Triple combinations are not studied. In prevalence peritonitis etc.), excessive mucus production, introital in 4.1% and 1.2% of the sigmoid-derived and the average level income earner. studies, only a marginal number of patients is on stenosis, bleeding after intercourse, malodor and ileum-derived vaginoplasties, respectively (Bouman triple therapy for BPH related LUTS. This number although anecdotal the potential for developing et al.). The rate of sexual satisfaction, which was Paradoxically, combination therapy can also might be underestimated. Patients might take, for diversion colitis, ulcerative colitis and cancer. usually assesed in a subjective fashion and without counteract some of the side effects. The sexual side example, short acting phosphodiesterase-5 inhibitors the use of Female Sexual Function Index (FSFI), was effects of alpha blocking agents or 5-alpha-reductase for erectile dysfunction or desmopressin for nocturnal The basic steps of intestinal vaginoplasty can be reported to be 85.7% (Davies et al., Hensle et al.). inhibitors can theoretically be attenuated by polyuria, besides combination therapy for BPH- summarized as; harvest of the intestinal segment phosphodiesterase inhibitors, for example6. related LUTS. (through median or Pfannenstiel laparotomy, Integrated multidisciplinary approach laparoscopy-assisted laparotomy and total Gender dysphoria and patients complaining about Dual combination thearapies It has to be emphasized that no evidence exists for laparoscopy), perineal incision, dissection of the this disorder have started to gain wider acceptance There is strong evidence for dual combination triple therapy. A clinician prescribing more than the neovaginal cavity, perineal-vaginal-bowel by the community which translated into increased therapies. The best studied combination consists of well-studied dual combination therapies, should warn anastomoses and neovaginal fixation to prevent number of patients engaging into this transition and alpha blocking agents combined with 5-alpha- the patient on possible side effects and interactions. prolapse (Bouman et al.). Sigmoid colon and ileum are seeking for treatment. Authorities and global reductase inhibitors. Since more than 10 years, level 1 the most commonly preferred intestinal segments for organizations have established standards related evidence exists. Several prospective randomized Combination therapy offers benefits vaginoplasty. Sigmoid colon possesses the advantages with the diagnosis and management (medical and controlled trials have been conducted and have In conclusion, combination therapy is a recognized of having a thicker wall, larger diameter, better surgical) of gender dysphoria which requires an shown both an additive effect of the dual therapy on and well-taken option for BPH related LUTS. Probably tolerance to trauma and more similarities to the integrated multidisciplinary approach. Vaginoplasty symptom relief as a decreased risk for disease about one in five to one in four patients is treated vaginal lining in terms of appearance, texture and represents the last step of the MTF transition progression in the long run7,8. with combination therapy, mostly 5-alpha-reductase natural lubrication (Colebunders et al.). Despite being process. Penile skin inversion technique is the most inhibitors with alpha-blocking agents and, secondly, stated as an advantage of intestinal segments, mucus investigated and therefore the most evidence-based It is important to realize that this combination therapy antimuscarinics with alpha-blocking agents. production may lead to excessive discharge and be the technique for vaginoplasty. Surgical outcome and should only be offered to patients with a certain Combination therapy offers advantages in onset and cause of malodor, especially when ileum is used. sexual function associated with this technique are prostate volume. Alpha-blocking agents will have an magnitude of effect of symptom relief in patients with generally acceptable to good. Using additional immediate effect voiding symptoms, whereas BPH-related LUTS. Increased costs and side effects are Laparoscopic harvest of the bowel for vaginoplasty was urethral and penoscrotal flaps may provide benefit 5-alpha-reductase inhibitors will result in a decreased the down side of this treatment option. introduced in order to minimize the inevitable in terms neovaginal depth and lubrication. prostate volume in the long run. The total symptom morbidity associated with open transperitoneal Intestinal vaginoplasty is a viable alternative, improvement with the combination treatment is The key lies in selecting the appropriate patients for a surgery. The length of harvested segments vary especially for secondary procedures. Overall, the higher than the symptom relief achieved by either specific combination treatment. In this way, the considerably, ranging from 7,5 cm to 20 cm. Different outcome of vaginoplasty with pedicled bowel monotherapy. It is not useful to prescribe 5-alpha- benefit outweighs the risks. Combining more than folding techniques (U-pouch, J-pouch, detubularization segments does not seem to be inferior to the penile reductase inhibitors if the patent is not motivated to two medications is not well-studied and is probably and retubularization technique) can be utilized to skin inversion technique. There is a need for take the medication for at least six months. not often done in real-life practice. In difficult-to-treat create a neovaginal pouch. Depending on the vascular prospective randomized studies with standardized patients with persisting symptoms, it can be anatomy of the patient, the intestinal graft can be surgical procedures, larger patient cohorts and The down side of combination treatment is the considered at an individual patient level. The patients transferred to the perineum in an isoperistaltic or longer follow-up period in order to make a valid increased risk of side effects associated with has to be warned about possible interactions and antiperistaltic fashion to minimize the tension on the comparison between the available vaginoplasty prescribing two active components with different increased risk for side effects. Cost might also be vascular pedicle (Bouman et al.). Usually a two-finger- techiques and identify the “ideal” one. working mechanisms. It is generally believed that, if high. wide space between rectum and urethra is created by side effects occur, they are reversible after therapy blunt dissection. Fixing the neovagina to the sacral Editorial Note: Due to space constraints, the cessation9. Adequate patient selection is key for Editorial Note: Due to space constraints, the promontory, the uterosacral ligament and adjacent reference list can be made available to interested having a good benefit-risk ratio. reference list can be made available to interested muscle fascia of the pelvic floor are the commonly readers upon request by sending an email to: readers upon request by sending an email to: applied maneuvers to prevent prolapse (Bouman et al., [email protected] Alpha-blocking agents combined with antimuscarinics [email protected] Moudouni et al. Karateke et al.). is a second well-studied dual combination treatment Saturday 17 March in male LUTS patients with predominant or residual Saturday 17 MSaturday 17 March In a recent review, which included 21 retrospective 10.15-15.35: Meeting of the EAU Section of storage symptoms. There exists level 1 evidence that 10.15-14.00: Meeting of the EAU Section of studies and 894 patients, the prevalence and Genito-Urinary Reconstructive Surgeons in male patients with a minimum threshold storage Female and Functional Urology (ESFFU), severity of periprocedural complications were (ESGURS); Updates in genito-urinary symptoms, a fixed dose combination of an alpha- Management of complex cases in male and reported to be low after intestinal vaginoplasty reconstruction blocking agent with an antimuscarinic improves the female functional urology (6.4% and 8.3% for sigmoid-derived and ileum- response in comparison to monotherapy10,11.

Saturday, 17 March 2018 EUT Congress News 15 Residual fragments - an ongoing headache after fURS Patient follow-up and counselling are crucial in renal stone cases

Prof. Dr. Arkadiusz Miernik Dept. of Urology Medical Centre - University of Freiburg Freiburg (DE)

The surgical treatment of urolithiasis has evolved substantially over the last three decades. Open surgery has been replaced by endoscopic techniques. In addition, new disintegration energy sources such as holmium laser lithotripsy gained supremacy in endourological theaters. The role of shock wave lithotripsy (SWL) has been decreasing, however. Figure 1: High-risk (A) and low-risk (B) stone formers with (green line)/without RF (blue line) (according to Hein et al. 2016)3 The widespread use of SWL led to the introduction of the term “clinically insignificant residual fragments” (CIRF) to urological vocabulary. These stone fragments Our study’s most important finding was that 33.3% significant ergonomic improvements. Conventional References are defined as post-lithotripsy disintegrates measuring of the low-risk stone patients with RFs after RIRS master-slave systems for laparoscopic surgery in 1. De la Rosette J, Denstedt J. Update from third 4mm or less in diameter. From the practical experienced an ipsilateral SRE, while low-risk urology such as DaVinci® might also prove useful for international consultation on stone disease. Springer; perspective, it is assumed that these fragments pass individuals with no RFs suffered no SRE on the stone retrieval, particularly for large and very large 2017. spontaneously through the urinary tract without ipsilateral side (p < 0.001). renal and ureteric calculi2. 2. Hein S, Miernik A, Wilhelm K, Adams F, Schlager D, causing the patient any clinically relevant conditions. Herrmann TR, et al. Clinical significance of residual Residual fragments (RF) may also remain in the After the initial euphoria that accompanied the Residual fragments are clinically important fragments in 2015: impact, detection, and how to collecting system after any kind of surgical intervention introduction of highly miniaturized endoscopic There is now high quality evidence and knowledge avoid them. World Journal of Urology. also, especially after shock wave lithotripsy (SWL), instruments and advanced lithotripsy systems allowing regarding RF after RIRS that confirm that RFs are 2016;34(6):771-8. percutaneous litholapaxy (PCNL), and retrograde safe, rapid, and precise treatment of urinary stones, clinically important. They affect significantly the 3. Hein S, Miernik A, Wilhelm K, Schlager D, Schoeb DS, intrarenal surgery (RIRS). the long-underrated problem of RFs might indeed give patient’s post-interventional clinical course. Low-risk Adams F, et al. Endoscopically determined stone the endourologist a headache. stone formers benefit especially from complete stone clearance predicts disease recurrence within 5 years after In recent years a shift has occurred worldwide towards clearance. Differences between patients with or retrograde intrarenal surgery. Journal of Endourology. RIRS as represented by flexible ureteroscopy (fURS) in There is now evidence that endoscopically-determined without RF become apparent over the long term, 2016;30(6):644-9. combination with laser lithotripsy. fURS enables RFs are an independent predicting factor for SRE in probably due to a delayed Nidus effect in recurrent relatively “straightforward” and rapid access to the low-risk stone formers, and that they threaten the stone formation. The term “clinically insignificant rest Saturday 17 March upper urinary tract, allowing the endourologist to postoperative course especially over longer follow-up fragments” (CIRF) should therefore be abandoned. 10.15-14.30: Meeting of the EAU Section of inspect all its areas and target stones easily. periods. Thus every effort must be made to achieve Urolithiasis (EULIS) complete stone clearance after endoscopic The awareness that RF may not always be avoidable Management of stones: Advancing technology, This trend is affecting both the absolute number of interventions and SWL to treat upper urinary tract means that conscientious patient follow-up and increasing experience and changing concepts. fURS procedures for urolithiasis-related interventions urolithiasis. Patients presenting RF are at risk for counselling are extremely important in case of RS after Where are we in 2018? and stone size. Large renal stones (LRS) also tend to be (ipsilateral) SREs requiring medical and/or surgical treatment. treated by RIRS. Because of the retrograde route’s interventions. anatomical limitations, namely a relatively thin ureter diameter and access sheaths (UAS) smaller than those The lessons we learned from this evidence are that: used in PCNL, LRS extraction can become very • the current surgical management of urinary stones IPSEN SATELLITE SYMPOSIUM 2018, 33RD ANNUAL EAU CONGRESS, COPENHAGEN time-consuming. To overcome this obstacle, several should always aim for total stone clearance, and disintegration concepts have been developed. One • that patients with miniscule RFs should not be recommends the creation of very small pieces (of stone declared stone-free. dust, or sand) that pass spontaneously after treatment1. What has the future in store for us? Optimising patient management Admittedly, little is known about the natural history and Several technical improvements have been validated in clinical relevance of RF on patients’ course or their vitro and in small case series. SWL technology is in urogenital cancers impact on subsequent stone-related events (SRE). Little providing new camera systems for continuous has been published on long-term outcomes, and the monitoring of SWL head coupling during the evidence level in what has been reported is low. Most procedure, which might significantly decrease the Date: 18:00–19:30, Saturday 17 March 2018 publications discuss case series, and even the RF number and energy levels of shockwaves to achieve Venue: Green Area, Room 2 (Level 0), Bella Center, Copenhagen definition (size, detection) and follow-up strategies are comparable results and high stone-free rates. quite heterogeneous. In the literature, the postoperative Publications addressing new lens designs have also Chaired by Dr Maria Ribal (Spain) observation of patients with RF ranges from 15 months reported greater focusing precision and efficacy. to 4.9 years. More interesting, are retreatment rates Interestingly, a novel technology described as ‘burst between 19.6 and 58.6% during follow-up2. wave lithotripsy’ might also enhance SWL’s efficacy. Agenda

Status quo Some interesting future developments should be Time Topic Speaker Is the presence of RS after stone interventions a reason discussed concerning the RIRS techniques now leading to worry? Several investigations were conducted to among the modalities applied in modern stone 18:00–18:05 Welcome and introduction Dr Maria Ribal answer this question. Our group assessed stone- therapy. 18:05–18:30 The significance of testosterone and gonadotropin suppression in advanced Dr Peter Busch Østergren related events (SRE) requiring retreatment in a series prostate cancer treatment of 100 consecutive patients treated by RIRS for renal First, innovations in disintegration technology are most stones and evaluated potential risk factors thereof3. We welcome and important if RFs are to be avoided. 18:30–18:55 Predicting the future of PDD – blue skies or dark clouds Pr Morgan Rouprêt defined RF as fragments measuring <1mm (i.e., Present-day Ho:YAG lasers are the gold standard in 18:55–19:20 Current strategies and future challenges in 2nd line therapy Pr Petri Bono fragments too small for retrieval). Our primary endoscopic lithotripsy in both RIRS and PCNL. The in advanced RCC outcome was the incidence of SRE requiring medical or latest technological innovations are aiming for safer surgical treatment during the follow-up period. The and faster disintegration achieving similarly-sized 19:20–19:30 Discussion and closing remarks Dr Maria Ribal secondary parameters we investigated were SRE, time fragments. Holmium laser devices now offer higher to SRE, and late complications. energy and frequencies, but also longer pulses, causing less retropulsion and producing smaller To distinguish between RF related conditions and fragments (dust, stone sand). The management of patients with urogenital cancers continues to detection. In addition, new optical diagnostic tools can provide metabolic factors, our follow-up cohort was stratified advance, driven by the release of new clinical data and the progression real-time information on tumour invasiveness and grade to help into low- and high-risk stone formers. We also Second, we need better retrieval instruments such as of available interventional and imaging techniques. For the treatment differentiate tumour types and guide treatment decisions. of prostate cancer, hormone manipulation remains a key therapeutic considered obesity, high stone burden, and lower pole graspers and baskets. The size of novel endoscopic Finally, the treatment landscape of 2nd line advanced renal cell strategy. Recent data has provided new insights on the impact of stones as independent parameters, and included those instruments requires new concepts and designs of carcinoma (aRCC) has evolved rapidly during recent years, with androgen deprivation therapy on testosterone levels, compared with data in our statistical evaluation. extraction devices. New grasper designs cannot be data from clinical trials investigating the impact of targeted subscapular orchiectomy in patients with advanced disease. simply adopted from open stone surgery or semi-rigid therapies and immuno-oncology agents. The availability of new Mean follow-up was 59 months (31–69) in 85 out of 99 ureteroscopy for ureteral fragments. Ultimately, Advancements in imaging techniques have been crucial for improving agents and changes to treatment guidelines have optimised patients, among whom 26 (30.1%) suffered an SRE. completely new RIRS approaches need to be management of patients with non-muscle-invasive bladder cancer. management for patients with aRCC. Thirty-four of the 85 (40%) patients were high-risk developed. These include irrigation and suction Techniques such as photodynamic diagnosis (PDD), play a key role This meeting is initiated and funded by Ipsen. stone formers. Twenty-two of them experienced SREs devices, gluing agents, magnetic extractors, etc. in identifying suspect lesions, which may result in increased tumour (both sides) during follow-up (64.7%, p < 0.001). Eight of the 17 patients (47.1%) with SRF experienced an SRE Last but not least, the slow fusion of flexible on the ipsilateral side, compared with 13 (19.1%) of the ureteroscopy with master-slave robotic platforms is 68 without SRF (p = 0.022, hazard ratio 2.823, 95% currently a hot topic, similar to urologic laparoscopy. confidence interval [95% CI] 1.16, 6.85). Risk for an Several robotic systems for urolithiasis therapy have Please visit the Ipsen booth E15 ipsilateral SRE was unaffected by the presence of SRF been introduced. Despite some limitations in the active CBZ-ALL-000560 13 February 2018 among HRSFs p = 0.561). extraction of stone fragments, these solutions offer

16 EUT Congress News Saturday, 17 March 2018 Visit us in the

Exhibition hall Booth E57 TOOKAD® (padeliporfin) Vascular Targeted Photodynamic Therapy1 Marketing Authorization (EMA) granted by European Commission November 10th 20172

Together

Created by Steba Biotech from ref. 5 Non Thermal Light3 padeliporfin4

Date & Time: Sunday March 18 17:45 – 19:15 SYMPOSIUM Location: Blue Area, Room 5 (Level 0)

Chairman: M. Wirth, Dresden (DE) M. Wirth, Dresden (DE) F. Montorsi, Milan (IT) I.S. Gill, Los Angeles (US) Welcome Clinical Results (Ph. III) Active surveillance & TOOKAD® 17:45 - 17:50 17:50 - 18:10 18:10 - 18:30

A. Scherz, Rehovot (IS) A.R. Azzouzi, Angers (FR) M. Wirth, Dresden (DE) Focal Therapy & Non thermal light Procedure & Practical training Conclusion 18:30 - 18:50 18:50 - 19:10 19:10 - 19:15

TOOKAD (padeliporfin) 183 mg or 366 mg powder for solu�on for injec�on Pa�ents should avoid exposure to direct sunlight (including through windows) and all bright light Abbreviated prescribing informa�on – please consult the full summary of product characteris�cs before sources, both indoors and outdoors. For specific instruc�ons on light protec�on measures, see the prescribing. SmPC sect. 4.4. Erectile dysfunction. Erec�le dysfunc�on may occur even if radical prostatectomy is ▼ This medicinal product is subject to addi�onal monitoring. This will allow quick iden�fica�on of new avoided. Some degree of erec�le dysfunc�on is possible soon a�er the procedure and may last for more safety informa�on. Healthcare professionals are asked to report any suspected adverse reac�ons. than 6 months. Extra-prostatic necrosis. There may be extraprosta�c necrosis in the peri-prosta�c fat. Therapeu�c indica�ons: TOOKAD is indicated as monotherapy for adult pa�ents with previously Excessive extraprosta�c necrosis occurred as a result of incorrect calibra�on of the laser or placement untreated, unilateral, low-risk, adenocarcinoma of the prostate with a life expectancy ≥ 10 years and: - of the light fibres. In consequence there is a poten�al risk of damage to adjacent structures, such as the Clinical stage T1c or T2a, - Gleason Score ≤ 6, based on high-resolu�on biopsy strategies, - PSA ≤ 10 bladder and/or rectum, and development of a recto-urethral or external fistula. A urinary fistula has ng/mL, - 3 posi�ve cancer cores with a maximum cancer core length of 5 mm in any one core or 1-2 occurred in one case due to incorrect fibre placement. The equipment should be carefully calibrated and posi�ve cancer cores with ≥ 50 % cancer involvement in any one core or a PSA density ≥ 0.15 use the treatment guidance so�ware to reduce the risk of clinically significant extraprosta�c necrosis. ng/mL/cm3. Urinary retention/urethral stricture. Pa�ents with a history of urethral stricture or with urinary flow Posology and method of administra�on: TOOKAD is restricted to hospital use only. It should only be problems may be at increased risk of poor flow and urinary reten�on post the TOOKAD-VTP procedure. used by personnel trained in the Vascular-Targeted Photodynamic therapy (VTP) procedure. The Urinary incontinence. The risk of sphincter damage can be minimised by careful planning of the fibre recommended posology of TOOKAD is one single dose of 3.66 mg/kg of padeliporfin. TOOKAD is placement using the treatment guidance so�ware. The TOOKAD-VTP procedure is contraindicated in administered as part of focal VTP. The VTP procedure is performed under general anaesthe�c a�er pa�ents with any previous prosta�c interven�ons where the internal urinary sphincter may have been rectal prepara�on. Prophylac�c an�bio�cs and alpha-blockers may be prescribed at the physician’s damaged. Inflammatory bowel disease. TOOKAD-VTP should only be administered a�er careful clinical discre�on. Retreatment of the same lobe or sequen�al treatment of the contralateral lobe of the evalua�on, to pa�ents with a history of ac�ve rectal inflammatory bowel disease or any condi�on that prostate are not recommended. may increase the risk of recto-urethral fistula forma�on. Use in patients with abnormal clotting. Special populations. In pa�ents with severe hepa�c impairment TOOKAD should be used with cau�on. Pa�ents with abnormal clo�ng may develop excessive bleeding due to the inser�on of the needles In pa�ents with renal impairment or in elderly pa�ents no dose adjustment is needed. This medicinal required to posi�on the light fibres. product contains potassium. Illumination for photoactivation of TOOKAD. The solu�on is administered Interac�ons: The use of medicinal products that are substrates of OATP1B1 or OATP1B3 (repaglinide, by intravenous injec�on over 10 minutes. Then the prostate is illuminated immediately for 22 minutes atorvasta�n, pitavasta�n, pravasta�n, rosuvasta�n, simvasta�n, bosentan, glyburide) for which 15 seconds by laser light at 753 nm delivered via inters��al op�cal fibres from a laser device at a power concentra�on-dependent serious adverse events have been observed should be avoided on the day of of 150 mW/cm of fibre, delivering an energy of 200 J/cm. Treatment should not be undertaken in TOOKAD infusion and for at least 24 hours a�er administra�on. Medicinal products which have pa�ents where a Light Density Index (LDI) ≥ 1 cannot be achieved. See the SmPC for further instruc�ons. poten�al photosensi�sing effects (such as tetracyclines, sulphonamides, quinolones, phenothiazines, Contraindica�ons Hypersensi�vity to the ac�ve substance or to any of the excipients. Any previous sulfonylurea hypoglycaemic agents, thiazide diure�cs, griseofulvin or amiodarone) should be stopped at prosta�c interven�ons where the internal urinary sphincter may have been damaged, including least 10 days before the procedure with TOOKAD and for at least 3 days a�er the procedure. trans-urethral resec�on of the prostate (TURP) for benign prosta�c hypertrophy. Current or prior An�coagulant medicinal products and those that decrease platelet aggrega�on treatment for prostate cancer. Pa�ents who have been diagnosed with cholestasis. Current (e.g. acetylsalicylic acid) should be stopped at least 10 days before the procedure with TOOKAD. exacerba�on of rectal inflammatory bowel disease. Any medical condi�on that precludes the Medicinal products that prevent or reduce platelet aggrega�on should not be started for at least 3 days administra�on of a general anaesthe�c or invasive procedures. a�er the procedure. Special warnings and precau�ons for use: Tumour localisation. Before treatment, the tumour must be Fer�lity, pregnancy and lacta�on: Contraception. If the pa�ent is sexually ac�ve with women who are accurately located and confirmed as unilateral using high-resolu�on biopsy strategies based on current capable of ge�ng pregnant, he and/or his partner should use an effec�ve form of birth control to best prac�ce, such as mul�-parametric MRI-based strategies or template-based biopsy procedures. prevent ge�ng pregnant during a period of 90 days a�er the VTP procedure. Pregnancy and breast- Simultaneous treatment of both prostate lobes was associated with an inferior outcome in clinical trials feeding. TOOKAD is not indicated for the treatment of women. and should not be performed. Insufficient pa�ents underwent retreatment of the ipsilateral lobe or Effects on ability to drive and use machines: TOOKAD has no influence on the ability to drive or use sequen�al treatment of the contralateral lobe to determine the efficacy and safety of a second machines. TOOKAD-VTP procedure. Follow-up post TOOKAD-VTP. There is limited biopsy data beyond 2 years Undesirable effects: Very common (≥ 1/10): Urinary reten�on, haematuria, dysuria, micturi�on a�er TOOKAD treatment, so long-term efficacy has not been determined. Residual tumour has been disorders, perineal pain, male sexual dysfunc�on. Common (≥ 1/100 to < 1/10): Genito-urinary tract found on follow-up biopsy of the treated lobe at 12 and 24 months, usually outside of the treated infec�on, haematoma, hypertension, haemorrhoids, anorectal discomfort, abdominal pain, rectal volume, but occasionally within the area of necrosis. There is limited data on long-term outcomes and haemorrhage, hepatotoxicity, ecchymosis, back pain, urethral stenosis, urinary incon�nence, prosta��s, on poten�al consequences of post-TOOKAD local scarring in case of disease progression. At present genital pain, prosta�c pain, haematospermia, fa�gue, abnormal clo�ng, perineal injury. For undesirable TOOKAD-VTP has been shown to defer the need for radical therapy and its associated toxicity. Longer effects with an incidence lower than 1/100, please refer to the SmPC. follow-up will be required to determine whether TOOKAD-VTP will be cura�ve in a propor�on of Overdose: Limited informa�on. A prolonga�on of photosensi�sa�on is possible and precau�ons against pa�ents. Following TOOKAD VTP, pa�ents should undergo digital rectal examina�on (DRE) and have light exposure should be maintained for an addi�onal 24 hours. An overdose of the laser light may their serum PSA monitored, including an assessment of PSA dynamics (PSA doubling �me and PSA increase the risk of undesirable extraprosta�c necrosis. velocity). PSA should be tested every 3 months for first 2 years post VTP and every 6-months therea�er Prescrip�on status: BEGR in order to assess PSA dynamics (PSA Doubling Time (DT), PSA velocity). Digital Rectal Examina�on (DRE) Packages: 183 mg, powder for solu�on for injec�on, 1 vial; 366 mg, powder for solu�on for injec�on, 1 is recommended to be performed at least once a year and more o�en if clinically jus�fied. Rou�ne vial. The price will be published at www.medicinpriser.dk, when the product is on the market. biopsy is recommended at 2-4 years and 7 years post VTP, with addi�onal biopsies based on clinical/ The Prescribing Informa�on (FEB2018) has been rewri�en and/or abbreviated as compared to the PSA assessment. Radical therapy post VTP procedure. Limited informa�on is available regarding the European Medicines Agency approved SmPC (NOV2017), which can be requested free of charge from safety and efficacy of radical prostatectomy a�er TOOKAD-VTP. Photosensitivity. There is a risk of skin the Marke�ng Authoriza�on Holder: Steba Biotech S.A., 7 Place du Théâtre, L-2613 Luxembourg, and eye photosensi�vity with exposure to light post TOOKAD-VTP. It is important that all pa�ents follow Luxembourg. [email protected] the light precau�ons for 48 hours post-procedure to minimize the risk of damage to the skin and eyes. Adverse events can be reported to [email protected] 1 - SmPC TOOKAD®. European Medicines Agency November 2017 2 - Community register of medicinal products for human use: http://ec.europa.eu/health/documents/community-register/html/h1228.htm#EndOfPage 3 - Azzouzi et al. Lancet Oncol. 2017 Feb;18 (2): 181-191 4- WHO Drug Information, Vol. 20, No. 4, 2006 5 - Azzouzi et al. World J Urol. 2015; 33:937-944 Saturday, 17 March 2018 EUT Congress News 17 www.stebabiotech.com | [email protected] Is TURP safe in frail elderly men or is MIT better? Minimally invasive treatment (MIT) is recommended for frail elderly patients but studies are needed

Prof. Andrea Tubaro Table 1: Morbidity and Mortality of BPE surgery in elderly patients Department of Urology Authors Country and Study N° of Age at Mean Age Surgery Morbidity Mortality Comments and Limitations Interval enrolled inclusion (Years) Technique (%) (%) Sapienza University patients (Years) performed of Rome Rome (IT) Reich et al. Germany, 2002-2003 10654 - 71 TURP 11.10 0.10 Strength: Good sample size, prospective design. Limitations: No qualitative assessment of ageing status, not focused on elderly patients. Matani et al. Germany, 1996 166 > 80 82 TURP 26 1.20 Strength: Good sample size. Limitations: No qualitative assessment of ageing status, retrospective design. Wyatt et al. UK, 1989 94 > 80 - TURP 71 5 Limitations: No qualitative assessment of ageing Co-Author: F. Presicce, Rome (IT) status, retrospective design. Brierly et al. UK, 1993-1997 90 > 80 84 TURP 39 0 Limitations: No qualitative assessment of ageing The medical treatment of lower urinary tract symptoms status, retrospective design. (LUTS) secondary to benign prostatic enlargement (BPE) Mebust et al. US, 1978-1987 472 > 80 - TURP 22.60 0.20 Strength: Good sample size. is certainly a successful story in the field of urology. During the last two decades, the introduction of several Limitations: Dated, no qualitative assessment of ageing status, retrospective design. pharmaceutical agents has dramatically decreased the rates of BPE surgery all over the world and has Marmiroli et al. Brazil, 2008-2010 100 > 75 79 TURP, Open 20 1 Strength: prospective design. prostatectomy significantly postponed its indication over time. Limitations: No qualitative assessment of ageing status, no inclusion of frail patients. In addition, an increase in life expectancy associated Pichon et al. France, 2013-2016 60 > 75 84 Mixed (TURP, 22 1.70 Strength: Qualitative assessment of ageing status, with an increasing proportion of elderly men in general PVP, HoLEP) prospective design. population results in more octogenarians presenting Limitations: small sample size, different procedures bothersome LUTS, refractory to medications, requiring (TURP, PVP, HoLEP) evaluated together in the study. prostate surgery. Thus, the clinical scenario for prostate Elshal et al. Canada, 1998-2012 264 > 80 84 Laser Surgery 19.6 0 Strength: Good sample size, standardized collection surgery is evolving: nowadays patients, who undergo (HoLEP, PVP) of complication with Clavien-Dindo Classification. BPE surgery, may be generally older, with more severe Limitations: retrospective design, long study interval, comorbidities and with larger prostates, possibly no qualitative assessment of ageing status. necessitating more challenging procedures. Piao et al. Korea, 2009-2013 38/579 > 80 86 HoLEP 13.2 0 Strength: Prospective design, standardized collection of complication with Clavien-Dindo Classification. The difference between adult and frail elderly patients Limitations: Small sample size, no qualitative is fourfold: aging per se is considered a risk factor for assessment of ageing status. surgery, aging is associated with comorbidities, aging is associated with larger prostate volumes and aging patients have a limited life expectancy so that durability general population of Reich study. Wyatt et al., in 1989 of the population and to adopt a therapeutic strategy From these preliminary evidences laser surgery seem of the treatment effect can be of different importance. first assessed TURP outcomes in octogenarians, showed adapted to the level of vulnerability. to be an effective and safe option for elderly patients a significantly higher morbidity and mortality rate, 71% lowering morbidity, in particular the high-grade For years, transurethral resection of the prostate (TURP) and 5% respectively. A decade later, in 1996, Matani et Consequently, we should seek alternative therapeutic complications. However, no qualitative assessment of has been considered the gold standard for the relief of al. reported, in octogenarians undergoing TURP, a strategies to TURP in particular in the most vulnerable ageing status in the abovementioned studies has been prostate outlet obstruction (BPO) secondary to BPE. In morbidity rate of 26% and a mortality rate of 1.2%, portion of the elderly population. In recent years, performed, therefore no definitive recommendations fact, as shown by several evidences in the literature, respectively. In most recent series exploring the same several randomized clinical trials (RCTs) compared can be drawn in particular in the frailest segment of TURP provided a high rate of efficacy and long-term topic, a downward trend regarding complications different laser techniques versus TURP and open the elderly population. durability with an acceptable number of complications. (about 20%) and mortality (0-1%) has been found prostatectomy, showing lower morbidity of laser However, these data are mainly extrapolated from (Table 1); however morbidity remains persistently procedures and at least equivalent functional outcomes. In this subgroup of patients, Prostatic Urethral Lift e multicenter studies and meta-analyses with the vast higher than in the general population of Reich study. The advantages of laser prostate surgery included in PAE may be more attractive options. In fact as majority of patients generally approximately 65 to 75 particular a superior haemostatic ability in extrapolated from RCTs and real-life studies in general years old. Unfortunately very few studies, in general Nevertheless, except in the Pichon series, none of the anticoagulated patients, reduced blood losses and population, these therapeutic alternatives may be dated and with several methodological bias, specifically above studies performed a qualitative analysis of the consequently a diminished blood transfusion rate. performed in almost all cases under local anaesthesia addressed the efficacy and safety profile of TURP in ageing status. They focused only on age and had not However, the vast majority of patients enrolled in these as a day case with a very low rate of low-grade over 75 years old patients. made any distinction between patients with RCTs generally approximately 65 to 75 years old. A very complications. The most common adverse events harmonious aging and patients with pathologic aging. limited number of studies directly addressed the experienced in the studies were dysuria, haematuria, On the other hand, several minimally invasive While Pichon et al. classified their elderly population, efficacy and safety profile of laser procedures in over 75 and pelvic pain. These adverse events were mostly procedures for treating BPE [i.e.: vaporization with 532 according the brief geriatric assessment (BGA) and the years old patients. short-lived, typically resolving within two weeks nm Greenlight Laser, Holmium/Thulium Laser comprehensive geriatric assessment (CGA), into three without further sequelae. Nevertheless to our Enucleation (HoLEP/ThuLEP), Prostatic Urethral Lift groups: ‘‘vigorous’’, ‘‘vulnerable’’, and ‘‘sick’’. The Elshal et al. performed a retrospective analysis of their knowledge no studies have specifically assessed the (Urolift®), Prostate artery embolization (PAE)] have mean morbidity rate in this study was in line with the patients who underwent laser prostate surgery safety of these surgical procedures in frail elderly been developed in recent years. Preliminary other studies (22%) in ageing population, but it was between 1998 and 2012. They identified 264 patients. experiences with these techniques suggest a shorter significantly higher for the ‘‘vulnerable” and “sick’’ octogenarians, 16.5% of the enrolled population. For hospitalization, a reduced number of complications groups (44%) compared with the ‘‘vigorous’’ group this category the mean age at time of procedure was Standardised geriatric assessment and, for some of these methods, even the possibility of (15%) (p < 0.05). In this selected category the 84±3.5 years. Holmium laser enucleation of the In conclusion, the available evidences suggest that performing them as day-cases and with no need for complications was almost comparable with the general prostate was performed in 171 (64.7%), holmium laser octogenarians undergoing BPE surgery have general anaesthesia. The lower morbidity and the population of the Reich study. In addition BGA can ablation of the prostate in 16 (6%), holmium laser acceptable perioperative morbidity regardless of the higher safety profile of these procedures compared to predict a poor result of surgery, ‘‘vulnerable” and transurethral incision of the prostate in 13 (5%) and selected surgical procedure. However, ageing men are TURP could make them a particular attractive option in “sick’’ patients had a higher risk to keep their photoselective vaporization of the prostate in 64 a heterogeneous cluster of population and a frail elderly men. However, as well as for TURP, very indwelling catheter after the surgery compared with (24.3%). Procedures for octogenarians almost doubled standardised geriatric assessment should be the key few studies have specifically assessed the safety of ‘‘vigorous’’ patients. In line with Pichon study, Tai et al. in a decade, passing from 11% at the end of 2002 to instrument to better stratify patients according to their these methods in frail elderly patients and head-to- found that poor cognitive and functional statuses are 19% at 2012. Likewise, the most recent studies about surgical risk. Data extrapolated from RCTs in general head comparison studies with the TURP on this independent predictors for an increased risk of the safety of TURP in elderly, about 20% of population suggest that minimally invasive treatment particular population are not available. postoperative delirium in the elderly patients perioperative complications has been recorded even for should be preferred in (very) frail elderly patients; undergoing TURP. laser surgery. however, no conclusive recommendations can be draw Morbidity and perioperative outcomes without specific study on this topic. In this report, we collected the existing evidences about Lower complication risks However, the vast majority (82.3%) was low-grade morbidity and perioperative outcomes of different In synthesis, the collected evidences suggest that TURP complications (Clavien grade I-II); high-grade References techniques for treatment of BPE among frail elderly is burdened by a two-fold complication rate in ageing complications (Clavien grade ≥ III) were only 17.7% of 1. Presicce F, De Nunzio C, Tubaro A. Can Long-term LUTS/ patients. In 2008 Reich et al prospectively evaluated patients when compared with general population the total and no perioperative deaths occurred in the BPH Pharmacological Treatment Alter the Outcomes of morbidity, mortality and early outcome of TURP in more undergoing the same procedure. However this study. A longer operating time was an independent risk Surgical Intervention? Curr Urol Rep. 2017 Sep;18(9):72. than 10,000 patients. The mean age of the enrolled unfavourable clinical scenario is evolving over time. As factor for perioperative morbidity in octogenarians, 2. Pichon T, Lebdai S, Launay CP, Collet N, Chautard D, population was 71.1 years old, the mortality rate was suggested by the downward trend in morbidity and while functional outcomes were good and comparable Cerruti A, et al. Geriatric Assessment Can Predict 0.1% and the overall morbidity was 11.1%. The most mortality in most recent studies, we may speculate that with younger patients. Outcomes of Endoscopic Surgery for Benign Prostatic common complications during the first month were advancement in surgical techniques and devices has Hyperplasia in Elderly Patients. J Endourol. 2017 urinary catheter withdrawal failure (5.8%), re- probably lowered the risks of complications associated Similarly, Piao et al. evaluated prospectively the effect Nov;31(11):1195-1202. intervention (5.6%), symptomatic urinary tract with TURP in older frail population. Moreover, we of age on the efficacy and safety of HoLEP. 3. Elshal AM, Elmansy HM, Elhilali MM. Transurethral laser infections (3.6%), bleeding requiring transfusions should keep in mind that there is a wide heterogeneity surgery for benign prostate hyperplasia in octogenarians: (2.9%), and TURP syndrome (1.4%). Reich et al did not within the geriatric patients, with a considerable In this study, patients ≥80 years had significantly higher safety and outcomes. Urology. 2013 Mar;81(3):634-9. focus their attention towards frail elderly men in their variability of life expectancy and health status within rate of of hypertension, higher values of ASA scores, 4. Piao S, Choo MS, Kim M, Jeon HJ, Oh SJ. Holmium Laser study; however morbidity was significantly increased by the same age group. total prostate volumes, higher rates of urinary Enucleation of the Prostate is Safe for Patients Above 80 age, polymedication, and preoperative indwelling retention, and use of anticoagulants at baseline. Years: A Prospective Study. Int Neurourol J. 2016 catheter. This study has been considered the milestone Therefore, the quantitative assessment of age should Moreover, the mean operative time and enucleation Jun;20(2):143-50. with which to compare other studies on the same topic not be the only predictive factor to define a therapeutic weight were higher in octogenarians when compared due to the sample size and the accuracy with which it strategy in the elderly. As yet proposed by the European with younger patients. In addition, elderly men had a Saturday, 17 March was carried out. Urology Association (EAU) in agreement with the Society longer hospital stay time (2.9±1.8 days) than general 10.15-14.00: Meeting of the EAU Section of of Geriatric Oncology (SGO) for the management of population (2.3±0.7 days; p = 0.001). Nevertheless the Female and Functional Urology (ESFFU); In Table 1 we summarized the outcomes, morbidity and prostate cancer, a standardised geriatric assessment that morbidity rate assessed by Clavien-Dindo classification Management of complex cases in male and mortality rate from TURP in studies that directly takes into account the multidimensional aspect of aging (about 13%) and the functional outcomes were female functional urology addressed the frail elderly population, comparing to the would make possible to better identify the heterogeneity comparable regardless of age.

18 EUT Congress News Saturday, 17 March 2018 My journey in prosthetic urology Teaching is the most difficult task in surgery but is also the mark of an expert

Dr. Ignacio Moncada method for penile prosthesis complications is the you never introduce improvements. On the contrary, Dept. of Urology standard practice. This was my first “important” you need to analyze your results, particularly when Hospital Sanitas La paper, published in Journal of Urology and some of something goes wrong and make the changes and Zarzuela the pictures in the paper were used by others to innovation needed to do it better (improving your Madrid (ES) illustrate their presentations. (Figure 1) results).

Use of a penile extender ...2 Twenty years ago And last but not least, my final reflection is, in my infections were much more common, and removal opinion, the most important of all: to teach others of the prosthesis was the standard of care of those what you have learned. Teaching is the most difficult cases. The consequence was a fibrotic shortened task in surgery; you start by assisting an expert, next penis, very difficult to re-implant. We published for step is to be assisted by an expert, then would come the first time the efficacy of a penile stretcher in being assisted by someone less experienced than you They say that nothing happens by chance, everything facilitating re-implantation surgery. Now the use of and finally the most difficult is to assist someone less has a purpose and you only know that purpose when a penile extender is common practice for all patients expert than you, making you the expert. you are far along the journey. When you connect all with any kind of penile fibrosis before surgery. This the dots, then the picture appears. article prompted the medical use of a penile In surgery, you are at the top when you are mentoring extender, now a recommendation in the EAU Figure 1: This photo was part of the author’s first key other surgeons. If someone considers you his mentor, My journey Guidelines for the conservative treatment of publication on penile prosthesis complications his master in surgery, when he/she has a doubt of Mine is the fourth generation of doctors, I was Peyronie’s disease. what to do in a difficult case and calls you for an born with Medicine in my blood. When I was a opinion, that is when you can finally consider yourself medical student, in 1980, I spent three months in Dual implant in patients ...3 The popularity of radical time probably correlates with being decently good at an expert. US with a friend of my father who was a urologist. prostatectomy as a treatment for prostate cancer led it but committing in advance for the long haul I never thought that urology could be my specialty to an increasing number of patients with severe ED changes it completely. Commonly we have colleagues References but it turned out to be my passion too. In those and stress urinary incontinence. The usual treatment who are interested in everything: oncology, lithiasis, 1. Buckling of cylinders may cause prolonged penile pain days, I witnessed for the first time in my life a is first to correct the incontinence and then proceed incontinence, andrology but they do not focus on after prosthesis implantation: a case control study using penile implant. The patient was a diabetic with a with the penile implant in those patients still willing anything specific and try different areas. It is very magnetic resonance imaging of the penis. J Urol, 160; very large penis and I was astonished with the to undergo further surgery. The alternative would be hard to become an expert in anything if you don’t 67-71, 1998. procedure. to perform this double implant at the same time focus on one specific area with the intention of 2. Use of a penile extender to facilitate penile prosthesis through the same incision. We depicted in this paper developing that chosen area. re-implantation after removal for infection. J Urol, 165, So, I said to myself, I want to do this surgery. When I our technique of doing this procedure pioneered by 1048, 2001. finished medical school, I started training as a S. Wilson. Now, the double implant is also Study and practice are the basis of the learning 3. Dual implant in patients with incontinence and erectile resident doctor in one of the best hospitals in Madrid recommended as an option in the EAU Guidelines in process in surgery: understand what to do and do it dysfunction. J Sex Med; 3(2):367-70, 2006. (Gregorio Marañón) where I spent five years such patients. repeatedly. In penile prosthetic surgery you cannot 4. Inflatable Penile Prosthesis Implantation Without completing a fantastic urology residency. When I was fail, if there is an infection it won’t heal by itself, it Corporeal Dilation: A Cavernous Tissue Sparing a fourth-year resident I spent a few months in Boston Inflatable Penile Prosthesis Implantation Without will probably need removal of the device and this will Technique J Urol 183, 1123-1126, 2010. with Bob Krane’s group learning about Sexual Corporeal Dilation…4 Typically, the implant involves be a disaster. So you need to program your steps, 5. Abdominoplasty and scrotal z-plasty associated to penile Medicine and penile surgery. Irwin Goldstein and the dilatation of the cavernosal bodies to make carry them out in a systematic way with no hesitation prosthesis implantation in patients with buried penis J Iñigo Saenz de Tejada were the big names there and I enough space to insert the cylinders. We and no time for doubts, be quick and clean. If you Sex Med, Vol. 7, 403–464, 2010. kept up my connection with them for many years. demonstrated that this is not necessary in the virgin change your technique continuously it always will be They were the pioneers of Sexual Medicine and I was case, so you can avoid it with all the benefits of being a new one for you and everyone in the OR (and that’s Saturday 17 March lucky to be close to them at that time and for many less invasive: it saves surgical time decreasing not good!). 10.15-15.30: Meeting of the EAU Section of Genito- years afterwards. Iñigo moved to Madrid and complications, preserves complimentary erection and Urinary Reconstructive Surgeons (ESGURS), although he was not a surgeon he became my mentor avoids retraction of the penis helping to maintain the Analyze your results and get feedback from patients. Updates in genito-urinary reconstruction and my close friend until his premature death. penile length after implantation. Many implanters in Being systematic in your surgery does not mean that the world are using this technique now. When I finished my residency in urology, I took a position as urologist in Gregorio Marañón Hospital Abdominoplasty and scrotal z-plasty…5 This paper on and I was very fortunate to have a Head of penile prosthesis in obese patients with hidden penis Department, Carlos Hernandez, who wanted to give opened a discussion about the importance of the ENUCLEATION OF THE PROSTATE doctors responsibility very soon. He put me in cosmetic aspect in penile surgery including Peyronie’s using Hemera Pulsed Thulium laser charge of andrology at a young age. However, I liked disease, as well as the role of lengthening procedures surgery more than research, so I got involved in in patients with a short penis. with updated settings penile implant surgery and Peyronie’s disease surgery and started to publish, to participate in and These papers were innovative in the field and to organize courses and seminars. As we were reflected both the insight and the experience of based in a University Hospital with residents and surgeons interested in the search for better outcomes visiting doctors, we soon created a “school” with a for our patients. It is also true that innovation is style of implant that is still used today. We learnt wholly linked to constancy and permanence in any Dr J.B Roche from all the big names in Prosthetic Urology in the medical field. Receiving recognitions like the Nikolay Groupe Urologie Saint- Augustin - Bordeaux (Fr) world such as Steve Wilson, John Mulcahy, David Alekseevic Bogoraz Medal awarded by the Russian Ralph or Mariano Rossello just to name a few. But Association of Andrology in 2010, or the Brantely-Scott as much as with the masters, I also learned a lot Award of Excellence presented during AUA 2015 In this video, we will present a laser prostate enucleation using from the young people who were once residents reflect the appreciation of my peers. In the end and then became masters themselves- Juan I. however, the most important acknowledgment comes updated settings, along with a modified en bloc dissection. At last Martinez-Salamanca, Enrique Lledo, Javier Romero from our patients. year’s ESUT session, we showed an original approach to enucleation or Agustin Fraile just to mention a few. using a pulsed Thulium laser. Having come this far, I feel I am still learning every Penile prosthetic implantation day. Sharing my experience with my colleagues and Nowadays penile prosthetic implantation surgery urologists in training is very professionally satisfying, For better performance, we changed settings to achieve a better has an important role in the management of long may it last. bubble effect, thus achieving a clearer enucleation plane. organic end-stage erectile dysfunction. The European Guidelines on Erectile Dysfunction How to become an expert recommend the implantation of a penile prosthesis. The second part of this article is “How to become an We will show how the thulium laser used in a pulsed mode can be The evidence of high efficacy, safety and expert”; it sounds a little pretentious for me to combined with a minimally invasive endoscopic technique to treat satisfaction rates of both patients and partners is pretend to know how to become an expert as it robust. Nevertheless, outcomes are not always assumes I am one. But in any case, as this is the title I large prostatic adenomas. perfect, complications arise and malfunctions are have been given for this presentation at the EAU, I somewhat frequent. will outline my own experience. Probably this reflection can be applied to any discipline in life, it Mastering the surgical techniques for the implantation could be called “how to become an expert in of virgin cases but particularly when complications anything”. But for sure in my case it all comes from Pre-recorded video arise is a must for the modern urologist. Our my experience as a surgeon. experience, with around 1,000 penile prosthesis March, 17th implanted in the last 25 years, has allowed us to The first thing I believe to be fundamental is to get explore different aspects of prosthetic surgery and to help: find a mentor who can help you develop that make innovations that improve the surgical outcomes. image in your head of the best way to do something. 16:54 I want to take you with me on my journey in Mentors act like a role model, giving you something eUro Auditorium (Level 0) Prosthetic Urology which can be better done from the to emulate and to aspire to. I have had several standpoint of some landmark papers, breakthrough mentors in my life, but if I had to name only one that papers, that led to a change in penile prosthetic would be Iñigo Saenz de Tejada, he always supported surgery and prompted some other publications. These and inspired me. To have a good mentor is not easy, are examples of these papers: maybe is just a matter of luck, but it can make all the difference in your professional career. Procedure performed with 200 W Buckling of cylinders may cause ....1 This paper was the first to demonstrate the role of MRI in penile The second thing I consider having utmost importance Hemera ® Thulium Rocamed Laser prosthesis to assess the correct position and right is the commitment factor. Ask yourself: How long am I function. Since then the use of MRI as a diagnostic going to be doing this? Doing something for a long

Saturday, 17 March 2018 EUT Congress News 19 Oncological outcomes following robotic-assisted RC Tumour recurrence after RARC linked to biology, not to surgical procedure

Dr. Justin W. Collins and that the technique is evolving, with an increasing A multi-centre RARC series Dept. of Urology number of centres performing totally intracorporeal published by the EAU Scientific 6 Karolinska University RARC . Working Group (ESWG) Hospital identified that early recurrences Stockholm (SE) Despite the apparent advantages of RARC, debate at any site occured in 4.1% of remains as to whether minimally invasive surgery patients at three months, 19.8% negatively impacts survival outcomes, potentially due at 12 months and 25.4% at 24 to inadequate resection, suboptimal lymph node months20, which is equivalent to dissection or alteration of recurrence patterns due to early recurrence rates seen in ‘tumour seeding’ related to the pneumoperitoneum ORC series18,21-23. The ESWG or insufflation12-14. A recent multicenter study reporting series identified that distant early recurrences in laparoscopic radical cystectomy recurrences in the bones, lungs New cases of bladder cancer are diagnosed in (LRC) found 8.7% of patients with favorable and liver were most frequent approximately 110,500 men and 70,000 women each pathological characteristics (pT2 N0 R0 or less) and that pelvic lymph nodes year1. In 2018, it is predicted to be the fourth and developed disease progression in the first 24 months were the commonest site of twelfth most common malignancy in males and post-operatively, concluding that the local recurrence. This is also females, respectively in the United States2. 38,200 pneumoperitoneum may have contributed to these consistent with the pattern of patients in the European Union and 17,000 US patients relapses15. recurrences seen in previous die from urothelial bladder cancer each year1. studies of ORC and in autopsy Figure 1a: K-M estimates of recurrence free survival ORC vs RARC series21,24. Regarding ‘unusual Mortality rates have remained relatively stable in Another single-centre publication compared open recurrence patterns’14,17, they recent years2. At presentation approximately 20-30% radical cystectomy (ORC) with RARC, reporting a identified five patients (0.7%) of bladder cancers are muscle-invasive and would higher incidence of peritoneal carcinomatosis and with peritoneal carcinomatosis likely be fatal for patients within two years if left extraperitoneal lymph node recurrences in patients and two patients (0.3%) with untreated. Radical cystectomy and extended pelvic undergoing RARC and concluding that the distribution port site (wound site) lymphadenopathy provide the best chance for of distant recurrences differed between the two metastasis, which are both of long-term survival and are considered the standard of approaches14. The potential for ‘differences’ in low incidence and consistent care for clinically localized muscle-invasive bladder recurrence patterns was again recently noted by Dr. with published open series25. cancer and high-grade recurrent non muscle invasive Marzouk and colleagues from Memorial Sloan disease3. Kettering Center, when they reported oncological Whilst debate remains on the outcome updates from their randomized control trial potential for detrimental effects The incidence of bladder cancer increases with comparing open (ORC) to RARC16. Between 2010 and from RARC on early recurrence advancing age. Considering the increasing life 2013, 118 patients with clinical stage Ta-T3 bladder patterns, there is little evidence expectancy and the increasing proportion of elderly cancer were randomized to RARC (n=60) or ORC of an overall higher incidence of people in the general population, radical cystectomy (n=58). In this latest update the median follow-up for early recurrences following will be considered for a growing number of elderly these patients was 4.9 years (IQR 3.9, 5.9)17. They RARC. Early RFS rates correlate patients. However, radical cystectomy by any identified 44 patients with recurrences: 25 after ORC, closely with five-year RFS and approach is complex surgery associated with and 19 after RARC. There were 14 abdominal overall survival18 and current significant peri-operative morbidity in a susceptible recurrences in five RARC patients, and four evidence from cumulative patient cohort who are frequently elderly with recurrences in two patients following ORC. analysis indicates satisfactory Figure 1b: K-M estimate comparing RFS between patients with non-favorable (pT>2 or associated co-morbidities. The risks of surgery medium and long-term RFS N+ or R+) and favorable pathological characteristics (pT≤2 N0 R0) therefore need to be balanced with the benefits of Concluding that although the RCT revealed no rates and cancer specific treatment4,5. significant difference in disease recurrence rates or survival19,22. In a recent review cancer-specific survival between RARC and ORC, they RFS rates at two years post-operatively ranged from associated with extensive metastases at multiple Potential advantages of robotic –assisted radical had observed patterns of recurrence based on 67-81% in RARC series22. Even papers highlighting sites24. In RARC series the incidence of peritoneal cystectomy (RARC) include reduced complications6, surgical technique, which were of interest. Stating unusual recurrence patterns as a possible indicator of carcinomatosis has been found to be low at 3.5%, less intra-operative blood loss due to the prolonged that the study was not powered to establish detrimental effect have not shown an increased even with long-term follow-up19. pneumoperitoneum, quicker return of bowel function, differences in patterns of recurrence17. incidence of recurrences compared to the ORC, in fact shorter hospital stay and earlier return to normal in both these series the overall incidence of recurrence Review of patients in the ESWG series with peritoneal activities, which would all theoretically allow more It is recognised that early recurrences are a poor was lower in the RARC group14,17. carcinomatosis and port-site metastasis revealed all immediate administration of adjuvant chemotherapy prognostic indicator, which correlates closely with patients to have high-grade urethelial cancer20. Four when required7. RARC has been shown to be five-year RFS and overall survival18. However, the Recurrence patterns of the five patients with peritoneal carcinomatosis advantageous in elderly patients and other current evidence for long-term outcomes following Previously hypothesised potential negative effects of presented with multiple metastases and 80% had susceptible groups8. The combination of RARC with an RARC shows acceptable oncological outcomes RARC, such as insufflation, the pneumoperitoneum upstaging of disease, from organ-confined to enhanced recovery program has been shown to comparable to open series19. A multi-centre study and methods of specimen extraction remain non-organ confined disease and only one (20%) further reduce the recovery time after cystectomy9,10. analyzing 702 RARC patients with a minimum of five unproven. Recurrence patterns attributed to the received NAC. These findings further indicate that years follow-up (median 67 months) reported a pneumoperitoneum and insufflation include peritoneal carcinomatosis from tumour seeding is The number of RARC’s performed in the United States five-year recurrence- free survival (RFS) of 67%. peritoneal carcinomatosis and port site metastasis14. related to tumour biology rather than the is steadily increasing, however, <20% of radical Factors associated with any recurrence were positive Peritoneal carcinomatosis incidence has been found pneumopertineum or other ‘effects’ of a RARC cystectomies are currently performed robotically11. lymph nodes, non-organ confined disease, and to be as high as 19% in bladder cancer patients at approach. Hypothesising that tumour biology is the Indications are that RARC is gradually being adopted positive surgical margin rates (all p<0.001)19. autopsy, but importantly it is most frequently main causative factor for early recurrence is also consistent with the laparoscopic cystectomy series that described unusual early disease recurrence patterns among patients with favorable disease characteristics (pT≤2N0R0)13. This series reported 8.7% of patients with pT≤2N0R0 developed recurrences within 24 months, with most of these patients showing progression to high-volume disseminated metastatic disease. Multi-variate logistic regression analysis identified pT stage as the only factor significantly associated with early recurrence in this multi-centre study13.

The ESWG series20 reported similar early recurrence rates (See Figure 1). But when you consider that approximately 80% of recurrences occur in the first two years [18,26], recurrence rates of 8.7% in pT≤2N0R0 in the first two years, equates to the five-year RFS of 89% in pT2N0 patients previously reported in a ‘Gold Standard’ ORC series21. Indeed, early recurrences with ‘favorable disease’ can be expected in a proportion of patients, pT2N0 has been shown to be a heterogeneous group with approximately a third being stratified as high-risk, showing oncological outcomes similar to pT3N0 disease27.

Accepted early indicators of oncological efficacy include PSM rates and lymph node yields3. Several cumulative analyses of RARC series have shown respectable PSM rates and median extended pelvic lymph node yields consistent with open series and RARC series11,19-22. PSM rates were strongly associated with pathological staging19-21.

Other factors consistently associated with early Figure 1: Unpublished K-M estimates from the ESWG multi-institutional database focusing on the centres performing totally recurrence are lymph node involvement, advanced intracorporeal RARC pathological stage and positive surgical margin

20 EUT Congress News Saturday, 17 March 2018 compared to organ confined the heterogeneity of aggressive disease, was also a significant urothelial cancer, it is difficult to risk factor for early recurrence accurately identify the best (HR=3.8 p<0.0001), as was a prognosis patients prior to PSM (HR 4.5 p<0.0001)20. surgery. To enable true Female gender was also seen comparison between to be a risk factor (HR 1.63 treatments, robust molecular or p<0.05) and has previously biological markers associated been identified as an with accelerated disease independent adverse prognostic progression are required, but factor for both recurrence and they are currently lacking in the progression of bladder cancer28. clinical setting. This inability to accurately predict metastatic Survival benefits risk pre-operatively is a Whilst reported early and late possible explanation for why outcome measures of smaller study numbers have oncological efficacy will rightly concluded differences in early dictate future adoption rates of recurrence patterns between 14 RARC, current evidence RARC and ORC . indicates survival benefits of radical cystectomy in elderly or Oncological efficacy co-morbid patients previously Indicators of oncological considered unsuitable for major efficacy following RARC, surgery29. The need for namely PSM rates and PLND oncological efficacy therefore yields are comparable to ORC needs to be increasingly series. Whilst several groups balanced with the risks of have indicated potential for surgery. It is recognized that an unusual recurrence patterns RARC approach is advantageous after RARC, their findings do in elderly patients and other not correlate with either an susceptible patient groups7 and increase in recurrence rates or there is evidence of changing decrease in cancer specific patient demographics in RARC survival. Current evidence series10. indicates that early recurrence rates and RFS rates following The potential additional RARC appear equivalent to

advantages of a totally published ORC series. Figure 2a: K-M estimates of recurrence free survival depending on pathological T stage intracorporeal RARC technique, Figure 2b: K-M estimates of recurrence free survival depending on pathological include less morbidity from the In all series, positive lymph Node stage operation, reduced transfusion nodes, non-organ confined rates19. In the ESWG cohort20, we see early recurrences rates and enhanced recovery8,10. Quicker recovery disease and PSM’s were associated with these variables on the Kaplan Meier following surgery should also result in improved associated with poor oncological outcomes, indicating estimates (See Figure 1), giving further evidence that opportunities for earlier administration of adjuvant tumour recurrence following RARC are primarily early recurrences following RARC are primarily chemotherapy, when pathological results or early related to tumour biology and not the modality of related to tumour biology and not the modality of recurrences indicate the need8. surgical treatment. Friday 16 March surgical treatment. On regressional analysis of the 12.30-15.45: Urology Beyond Europe, Joint ESWG series, the risk of recurrence was associated Although the selection biases of patients for optimum Editorial Note: Due to space constraints, the Session of the European Association of Urology with positive compared to negative lymph nodes management outside of prospective randomized reference list can be made available to interested (EAU) and the Korean Urological Association (N1 vs N0 HR= 3.6 p<0.0001 and N2 vs N0 HR=5.6 controlled trials can limit direct comparison with readers upon request by sending an email to: (KUA) p<0.0001). Pathological non-organ confined, when alternative treatments, it is also evident that due to [email protected]

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204_17_ENDOCAM_Logic_4K_270_194_en_EAU18_day1.indd 1 05.02.2018 09:58:06 Saturday, 17 March 2018 EUT Congress News 21 Antibiotic treatment’s collateral effects Antimicrobial stewardship, critical antibiotic use are crucial to minimise bacterial infections

Dr. José Medina-Polo Antibiotic selection microorganisms. Moreover, a proper indication is suspected, the patient must be considered to be Department of A correct selection of antibiotics is of paramount regarding prophylaxis is required (indication and “highly infectious”, and the protocol for isolation Urology importance. Some drugs not frequently prescribed no indication, duration, type of antibiotic). When must be started. Moreover, there is a high risk of Hospital Universitario in this setting, such as fosfomycin and the infection is diagnosed, the selection of environmental contamination in the room when a C. 12 de Octubre nitrofurantoin, are usually associated with a lower antibiotics may be challenging as anywhere from difficile infection occurs. Madrid (ES) resistance rate, and they are considered an 15% to 45% of infections due to ESBL-producing attractive alternative in the management of urinary bacteria are not appropriately managed. On the In 2013, The Centers for Disease Control and tract infections with the isolation of ESBL- one hand, an adequate empirical treatment must Prevention (CDC) classified the infection due to C. producing bacteria and MDR microorganisms. be chosen. On the other hand, broad-spectrum difficile in the highest “hazard level” for Fosfomycin shows good activity against common antibiotics should be avoided. Moreover, antibiotics development of antibiotic resistance, on the same uropathogens including ESBL-Enterobacteriaceae. must be selected while taking into account the level as carbapenem-resistant Enterobacteriaceae. Parenteral administration of fosfomycin can be appropriate dosage, an adequate route of Regarding the prevention of C. difficile, it should be A primary concern for worldwide healthcare effective whether urinary tract infections are administration, and administration timing. Before borne in mind that spores are highly resistant to systems is the increasing incidence of antibiotic caused by ESBL Enterobacter, Pseudomonas selecting an antibiotic treatment, previous cultures alcohol. Thus, alcoholic solutions for hand-washing resistance in healthcare-associated infections (HAIs) aeruginosa, and vancomycin-resistant- must be reviewed as high resistance rates are may be not efficacious. C. difficile infection may also and also in the outpatient setting. Moreover, the Enterococcus. However, fosfomycin is not reported after previous antibiotic therapies. be presented as a recurrent disease, and it is emergence of multidrug-resistant organisms recommended for pyelonephritis as low Another critical point is asymptomatic bacteriuria, associated with increased mortality. Antibiotic (MDRO) is a worrisome point as the selection of an concentrations in serum and renal tissues are which does not require treatment except in treatment in the case of C. difficile infections should appropriate antibiotic treatment is a challenging achieved. Nitrofurantoin also offers good efficacy pregnant women or previous to urological be chosen according to clinical characteristics and task. against Enterobacteriaceae such as E.coli, instrumentation. Therefore, patients with urinary severity and may include metronidazole, Klebsiella, and Enterobacter. However, it is not catheters, pyuria or malodorous urine without fever vancomycin, or fidaxomicin. Faecal transplantation Several definitions for MDRO have been proposed effective against Proteus and Pseudomonas. or chills should not be treated with antibiotics. can be required in patients with a severe and such as those microorganisms with resistances to recurrent infection. three or more antibiotic classes. It is recommended to For severe infections caused by MDRO including Infectious complications follow the definition by the Centers for Disease methicillin-resistant Staphylococcus aureus (MRSA), Infections due to Clostridium difficile are another In summary, the following measures are Control and Prevention, which considers MRDO as Acinetobacter baumanni, P. aeruginosa and complication related to antibiotic treatment. It is the recommended in order to minimise the emerging microorganisms, predominantly bacteria, that are carbapenemase-producing bacteria, antibiotics such most common cause of infectious diarrhoea among growth of multidrug-resistant organisms (MDRO): resistant to one or more classes of antimicrobial as tigecycline and colistin are indicated. Collaboration hospitalised patients. This type of infection has risen agents. Certain types of microorganisms deserve with an infectious disease physician is advised for sharply over the last decades. C. difficile may be • Training regarding MDRO, local microbial special attention such as extended-spectrum these patients. found in faecal flora in up to 20-50% of hospitalised prevalence, and resistance patterns, and beta-lactamase (ESBL) producing Enterobacteriaceae patients as asymptomatic colonisation or while prescription of antibiotics are required for or those resistant to carbapenems, Enterococcus Among urological patients, high rate of antibiotic producing an infection. The high incidence of C. healthcare providers; resistant to vancomycin, and Methicillin-resistant resistance has been reported due to specific risk difficile as an asymptomatic carrier both in • Information about prevention of infections is not Staphylococcus aureus (MRSA). factors such as urinary catheters and surgery during community and hospital settings is related to chronic only necessary for healthcare personnel, it should hospitalisation. According to data from our antibiotic use and with antibiotic resistance. The also include everybody in contact with the In recent years antifungal resistance is also increased, department, there is a higher risk of MDRO isolation bacteria produce endotoxins, which confer the patients and relatives who visit them; in particular in case of Candida glabrata and in a patient with immunosuppression [OR 2.57], organism’s virulence with a cytotoxic action on the • The prescription of antibiotics should be Aspergillus fumigatus. Fungal infections are more urinary lithiasis [OR 2.309], a prior urinary infection bowel mucosa that causes the infection with a clinical adequately indicated and justifiable, avoiding common in patients with immunosuppression, those [OR 2.45], and an indwelling urinary catheter prior to presentation range from uncomplicated diarrhoea to broad-spectrum antibiotics; with cancer and transplant recipients. MRDO may be admission [OR 1.79]. The highest rates of MDRO were pseudomembranous colitis and colonic perforation. • Antibiotic prophylaxis according to the considered as a collateral effect of antibiotic found among patients with HAIs and a double-J stent Most of the patients with infection due to C. difficile recommendation by Best Practice Guidelines (EAU treatment. Another worrisome consequence related to and a nephrostomy tube. We have also analysed have had previous antibiotic treatments with and local microbiological and resistance rate). antibiotic treatment is Clostridium difficile infection. infections due to carbapenem-producing bacteria in broad-spectrum antibiotics (cephalosporins, Perioperative antibiotics should not routinely be Both the isolation of multidrug-resistant bacteria and patients hospitalised in our Urology ward, and each aminoglycosides, amoxicillin/clavulanic acid and maintained beyond the first 24 hours after Clostridium difficile are associated with high of them had a urinary catheter, and two out of 12 had fluoroquinolones). surgery unless there is an infection; morbidity and mortality rates, longer hospitalisation immunosuppression. • Antibiotic choice should be determined according and higher costs. It is estimated that MRDO infections Other risk factors for C. difficile isolation are an to a risk factor for MDRO; increase hospitalisation cost by 10-30%, and C.difficile A survey carried out in Germany reported that admission from a nursing home, the existence of • Improve adherence to measures for infection infections increase the hospitalisation stay by a mean urologists were more confident prescribing the correct severe underlying diseases, and the use of anti-ulcer prevention, including shortening, when possible, of nine days. dosage and duration of antibiotics. However, both medications. Moreover, mechanical bowel the duration of urinary catheterisation; urologists and non-urologists had poor knowledge preparation may increase the risk of C. difficile • Methods for enhanced microbiological diagnosis MDRO are commonly isolated in patients hospitalised about antibiotic stewardship. infection. It is estimated that the chance of a positive with rapid detection of resistance are advisable; in a urology ward with hospital-acquired infections. testing for C. difficile is 0.21%. In urological patients, and According to data from GPIU-study 2003-2013 (Global The main points for minimising resistance to C. difficile infections are more common after urologic • Antimicrobial Stewardship Programs dedicated to Prevalence Study on Infections in Urology) carried out antibiotics, selecting appropriate empirical procedures that require bowel use such as radical improving antibiotic are required and they have by the EAU Section of Infections in Urology (ESIU), antibiotic therapy, and optimising outcomes are an cystectomy. The incidence of C. difficile infections demonstrated a reduction in the incidence of among patients hospitalised in a urology ward and adequate knowledge of risk factors as well as ranged from 2.2% to 11.7% after a radical cystectomy infections and isolation of MDRO bacteria and C. with healthcare-associated urinary tract infections, microbiological and resistance patterns for the in comparison with 0.02% after a prostatectomy and difficile infections. 45% of Enterobacteria and 21% of P. aeruginosa were isolation of multiple-drug resistant 0.23% after a nephrectomy. When C. difficile infection multidrug-resistant. Moreover, the resistance rate for References imipenem was 8% (Figure 1 summarise resistance 1. Cai T, De Nunzio C, Salonia A, Pea F, Mazzei T, Concia E, rate from GPIU study). Higher resistance rates were et al. Urological infections due to multidrug-resistant reported in a case of urosepsis. bacteria: what we need to know? Urologia 2016;83:21–6. doi:10.5301/uro.5000123. Furthermore, MDRO are isolated as a hospital- 2. Global Alliance for Infections in Surgery Working Group. acquired or healthcare-associated infection. This A Global Declaration on Appro-priate Use of term includes when patient was hospitalised within Antimicrobial Agents across the Surgical Pathway. 90 days before the infection, or receives long-term Surgical Infections 2017;18:846–53. doi:10.1089/ healthcare, intravenous therapy, specialised wound sur.2017.219. care, or hemodialysis. ESBL-producing bacteria are 3. Heinlen JE, Salinas L, Cookson MS. Clostridium difficile also isolated in a community setting. Misuse and Infection in Contemporary Uro-logic Practice. Urology the indiscriminate use of broad-spectrum 2018;111:23–7. doi:10.1016/j.urology.2017.06.035. antibiotics are related to the growing frequency of 4. Lebentrau S, Gilfrich C, Vetterlein MW, Schumacher H, microorganisms that are resistant to antibiotics. Spachmann PJ, Brookman-May SD, et al. Impact of the Inappropriate use of antibiotic agents in human medical specialty on knowledge regarding multidrug- and food producing animals also contribute to the resistant organisms and strategies toward antimicrobial development of antibiotic resistance. In particular, stewardship. Int Urol Nephrol 2017;49:1311–8. doi:10.1007/ there is a clear connection between the prescription s11255-017-1603-1. of fluoroquinolones and the incidence of resistant 5. Medina-Polo J, Arrébola-Pajares A, Pérez-Cadavid S, strains. Benítez-Sala R, Sopeña-Sutil R, Lara-Isla A, et al. Extended-Spectrum Beta-Lactamase-Producing Bacteria Therefore, in areas with higher resistance to in a Urology Ward: Epidemiology, Risk Factors and quinolones, they should be avoided as empirical Antimicrobial Susceptibility Patterns. Urol Int treatment. Moreover, ESBL-producing 2015;95:288–92. doi:10.1159/000439441. Enterobacteriaceae are also frequently resistant to 6. Tandogdu Z, Bartoletti R, Cai T, Çek M, Grabe M, other antibiotics such as fluoroquinolones and Kulchavenya E, et al. Antimicrobial re-sistance in aminoglycosides. Carbapenems are usually the urosepsis: outcomes from the multinational, multicenter antibiotics prescribed in the management of global prevalence of infections in urology (GPIU) study infections due to MDRO, especially those caused 2003-2013. World J Urol 2016;34:1193–200. doi:10.1007/ by ESBL-producing bacteria. However, s00345-015-1722-1. carbapenemase-producing bacteria are also emerging, and it is a worrisome problem as up to Saturday 17 March a 50% mortality rate has been described in 10.00-14.40: Joint meeting of EAU Section of patients with bloodstream infections with Andrological Urology (ESAU) and the EAU carbapenem-resistant Enterobacteriaceae. Section of Infections in Urology (ESIU) – When Furthermore, few treatment options are available basic science meets clinical practice for carbapenem-producing bacteria.

22 EUT Congress News Saturday, 17 March 2018 Office Urology: Meeting the challenges Prostate biopsy issues top agenda of ESUO

By Joel Vega the role of biomarkers in prostate cancer treatment. Schneider will look into pioneering experiences and The new EAU Section of Urologists in Office (ESUO) lessons from a fusion biopsy network in Switzerland. will focus on prostate biopsy issues during its ’first’ annual meeting, following its official launching last “We aim to have an interactive session as much as year in London. The topic is of prime concern to office possible, stimulating the audience to provide critical urologists with recent and still evolving changes in views and feedback back to the panel of speakers,” prostate cancer detection such as new imaging said Haas. Aside from Haas, chairing the session are techniques. three ESUO members including Dr. Horst Brenneis (DE), Dr. Stefan Haensel (NL) and Dr. Robert Schneider “We have headlined our meeting her in Copenhagen (CH) who will provide preliminary remarks and lead as “All about prostate biopsy in office,” as this reflects the case discussions. an important method in urologic office done in all countries,” said ESUO Chairman Prof. Dr. Helmut Haas said that as a new office under the auspices of Haas (DE). the EAU, the section is taking all efforts for it to achieve its aims. Haas said the session will be moderated by office urologists, with expert lectures by Profs. Maurice “Aside from promoting the ESUO to other EAU section Stephan Michel (DE) and Jochen Walz (FR), and offices and affiliates, we have conducted several Drs. Stefan Czarniecki (PL) , Stefan Haensel (NL), and surveys not only to find out the basic issues that Robert Schneider (CH). Michel will discuss indications concern office urologists but also to expand our for biopsy, patient’s preparation and biopsy contacts. We appreciate every little effort from our ESUO Chair Prof. Helmut Haas (left) with former EAU Sec. General Per-Anders Abrahamsson at at last year’s launching meeting procedures. Walz, meanwhile, will examine TRUS- partners, both current and potential, that will help us of the ESUO in London and MRI-guided biopsies, going through patient expand the network of office urology,” Haas said. selection, benefits, drawbacks and future prospects. “To all office urologists, send us an e-mail ([email protected]) with your expectations.” “Our section offers collaboration, especially based on Management of biopsy complications will be the fact that most of the new developments in discussed by Haensel, while Czarneicki will explore Special route itinerary diagnostics and non-surgical therapy have to be During the congress this week, the section has transferred to outpatients under outpatient Meeting Tip! created a “route itinerary” that will track and identify conditions. This means either in outpatient various meetings or sessions that are relevant or of departments or in urologic offices. Office urologists ESUO Session, All About Prostate Biopsy, interest to office urologists. know best the medical and patient-related Saturday 17 March 10.15-14.00 considerations and administrative rules under which “Our section has created an itinerary here in this can be done successfully,” Haas explained. Prostate biopsy is a core procedure in Copenhagen which flags and scores the congress’ urologic office. During the meeting all sessions according to their importance for office Haas said ESUO has been invited by the Slovak relevant aspects of prostate biopsy in an urologists. This will help our members or other office Urological Society to participate in the Slovak meeting office setting will be presented by urologists to easily identify which sessions can add as of office urologists in April, where he will not only recognized specialists: indication, priority to their congress agenda,” he said. present the ESUO’s goals and projects but also the procedures, the management of challenges and developments in office urology issues. complications, and modern imaging. Sharing its expertise The session is chaired by office urologists He also mentioned that aside from collaboration with Nevertheless, he emphasized that a lot needs to be who will focus on the outpatient situation. Aside from collaboration, the ESUO also offers to share other offices, the ESUO is also ready to offer its own done by the ESUO for it to adequately cover or its expertise expertise. address the issues faced by office urologists.

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Saturday, 17 March 2018 EUT Congress News 23 Introducing European Urology Oncology New journal to offer a multidisciplinary view of GU cancer treatment

By Loek Keizer audience including also number of papers submitted to the main journal, the “There is no intention to have any competition now non-surgical communities.” numbers of straight rejections or rejections after peer or in the future. Both journals will cover research in The EAU is gearing up to offer a new scientific journal review, so many of these are rejected despite their uro-oncology. Additionally, European Urology also besides the established titles of European Urology and European Urology Oncology quality. These papers may be given another chance for covers benign diseases, which we will not cover. It European Urology Focus. We spoke to the Editor-in- will be published online, publication under the EAU’s banner.” has the highest impact factor as it is the most Chief of European Urology Oncology, Prof. Alberto every other month. EAU highly-cited, most-read, most-distributed journal in Briganti (IT) about the journal’s mission, its intended members will automatically “Authors who might initially not have their research the field. We are a small journal compared to audience and place in the landscape of medical get access to the new journal. accepted by the editors of European Urology, but who European Urology, and there will not be any journal publications. Briganti: “The first edition is produce good quality papers are then given a chance competition between us.” Prof. Alberto Briganti coming up soon. We are to be considered for EU Oncology. I believe there is a “This is a new journal, and the EAU’s first official currently working on the first lot of research which cannot always be allocated (due Briganti anticipates more of a divergence between the journal that is fully devoted to the research of batch of papers that was accepted.” to space constraints) to the main journal. This is journals, but not in the short-term. “It takes time to set genitourinary (GU) cancers,” Briganti explained. common practice in the industry, and many journals up a new journal and make it fly properly. In the “The novel idea is to assemble an editorial team of Editorial team have sister publications in this way.” future, as we begin to receive more direct submissions, specialists from different GU-related disciplines who Chosen as the EU Oncology’s editor partly due to his we may end up featuring more and more articles will work together to create a multidisciplinary journal previous editing experience, Briganti previously within the area of pure medical oncology or in which different aspects of GU cancers such as served on the European Urology editorial board, and “Ultimately, our goal is to publish translational research,” he said. “Ultimately, our goal medical oncology, radiation therapy, urology, imaging, co-edited EU Focus, together with Mr. James Catto innovative and high-quality papers is to publish innovative and high-quality papers which pathology, molecular pathology are all represented.” (GB). He also served as guest editor for various issues are of course distributed and well-read among the GU of other medical journals. which are of course distributed and community. The journal’s high-quality evidence should The journal will feature a range of sections, well-read among the GU community. ultimately translate into practice-changing data.” encompassing original research and reviews, Serving as Associate Editors are medical oncologist discussions and some Guideline reviews. Briganti: Dr. Laurence Albiges ( FR), urologist Dr. Gianluca The journal’s high-quality evidence Role of medical journals “In GU cancers, prostate, kidney and bladder cancer Giannarini (IT), Prof. Ashish Kamat (US) who is involved should ultimately translate into Translating the research published in medical journals are of course most prevalent, but we will also feature in Urologic Oncology & Cancer Research and radiation into practice-changing data is exactly the goal of testicular, penile and other rarer cancers. We will oncologist Prof. Paul Nguyen (US). Managing Editor Ms. practice-changing data.” medical journals. “The literature that an EAU have new research coming in, and we are also Emma Redley is based in Sheffield (GB), where the membership provides should be useful for any commissioning reviews on several ‘hot’ topics. We editorial team of European Urology is also based. Initially, EU Oncology will draw on submissions to urologist. This way they can stay up to date and be actively commission systematic review, meta- European Urology. “Ultimately, we hope to receive aware of changes in practice or future directions of analysis, as well as opinion papers, on topics in “We have a dream team of editors with different more and more direct submissions, but as the journal practice,” Briganti said. He noted that a journal’s which there is interest.” backgrounds from all over the world, who are also key is in its infancy, James Catto and I decide which ultimate aim is to help improve patient care by opinion leaders in their respective fields,” Briganti article should go be considered for EU Oncology after publishing and circulating high-quality research, and In terms of target readers, European Urology Oncology said. “Together, we will endeavor to make this journal rejection from European Urology,” he added. direct the reader’s attention to new and evidence- is designed to serve every medical expert dealing essential for those publishing in the field. Competition based medicine. “We contribute to increasing the with GU cancers and their research, including is very high and we believe that if we insist on quality Whether the emergence of a new, GU cancer- adherence to good treatment by practicing urologists, medical oncologists, radiation therapists, and rigorous peer reviews, the journal will improve focused journal would affect the current balance of urologists,” he said. imaging specialists and general research scientists. and reach high standards.” contents of European Urology is difficult to say. “I don’t foresee such a change,” Briganti said. “GU European Urology, and soon, European Urology “Naturally, our core audience is the urologist,” Motivation cancer research is so wide, and there are so many Oncology are not only widely-cited journals, but are Briganti said. “Urologists are among the main The genesis of European Urology Oncology came from developments in terms of clinical and translational also discussed at meetings, eventually helping shape actors in GU treatment and represent majority of our the wealth of GU research that is submitted to European research. There will always be sufficient material medical guidelines. Briganti: “The ability to improve readers. But the scope of our journal goes beyond Urology. Roughly 80% of these submissions are related for both journals. The main journal will continue and change guidelines is the best that any journal can urology and this might attract attention from other to genitourinary cancers, with many of the submissions publishing high-quality material in the field of GU do. It means you are influencing the rules for good disciplines. Our ultimate aim is to have a wide deserving of an audience. Briganti: “If you consider the cancers.” clinical practice. This makes a journal great.”

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24 EUT Congress News Saturday, 17 March 2018 Predicting resistance to BCG therapy Emerging therapies for non-muscle invasive bladder cancer

Dr. Edmund Chiong receptor (VDR) in strong linkage disequilibrium, There are also phase 1 and 1/2 studies in progress, President, Singapore rs1544410 and rs731236 were correlated to recurrence that combine BCG with either atezolizumab or 13 Urological Association risk in an Asian cohort of NMIBC patients pembrolizumab for the treatment of NMIBC . Director of Urologic (unpublished data). In the same cohort, However, a cautionary point to note is that the use of Oncology & Research, polymorphisms in cytokine genes such as IL17A ICBs should be limited to patients with tumours Department of (rs2275913) and IL18R1 (rs3771171) were also found to expressing these proteins. Molecular analysis of Urology associate with BCG immunotherapy response patient tumours and immune cells will determine the National University (unpublished data). best therapy for patients. Health System (NUHS) Singapore (SG) Additionally, studies have also begun to evaluate References epigenetic changes, which can alter gene activity and 1. Kamat AM, Li R, O’Donnel MA, et al. Predicting expression outside of gene sequence changes, as Response to Intravesical Bacillus Calmette-Guérin For decades, Bacillus Calmette-Guerin (BCG) predictors of patient response to BCG. In one study Immunotherapy: Are We There Yet? A Systematic immunotherapy has been the standard of care to using a cohort of BCG treated T1G3 bladder carcinoma Review. European Urology. DOI: 10.1016/j. prevent recurrence and progression of the disease patients, the methylation profile of a panel of tumor eururo.2017.10.003 after tumour resection, in non-muscle invasive suppressor genes (TSG) were assessed and differential 2. Kamat AM, Dickstein RJ, Messetti F, et al. Use of bladder cancer (NMIBC) patients. Despite the efficacy methylation patterns of several TGS between patients fluorescence in situ hybridization to predict response to of this treatment, a significant fraction of patients will with recurrence or progression were found9. bacillus Calmette-Guerin therapy for bladder cancer: ultimately develop recurrence and progression. results of a prospective trial. J Urol 2012;187:862–7 An apparatus (4–5 cm length, with 9 short needles) used for Differences between populations 3. Bilen CY, Inci K, Erkan I, Ozen H. The predictive value of BCG vaccination in Japan, shown with ampules of BCG and Patients who fail BCG therapy can also incur higher The allele frequencies of SNPs between populations purified protein derivative results on complications and saline (Photo: Y.Tambe/Wikipedia) medical costs due to the need for multiple procedures of different geographical background and ethnicity prognosis in patients with bladder cancer treated with and closer surveillance for cancer recurrence. should be taken into consideration when developing bacillus Calmette-Guerin. J Urol 2003;169:1702–5 Furthermore, patients who develop disease SNPs as predictive markers of response to BCG 4. Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. The 8. Chiong E, Kesavan A, Mahendran R, et al. NRAMP1 and progression often have a poorer chance of survival. therapy. Genetic association studies are usually side effects of Bacillus Calmette-Guerin in the treatment hGPX1 gene polymorphism and response to bacillus performed in a homogenous cohort. Whether these of Ta T1 bladder cancer do not predict its efficacy: results Calmette-Guerin therapy for bladder cancer. Eur Urol Clinicopathological parameters such as tumour grade, genetic predictors can be applied globally requires from a European Organisation for Research and 2011; 59:430–7. stage, multiplicity, recurrence rate, the concomitant validation. For an example, a Southern European Treatment of Cancer Genito-Urinary Group Phase III Trial. 9. Agundez M, Grau L, Palou J, et al. Evaluation of the presence of carcinoma in situ (CIS), gender and age population study reported a panel of eight immune Eur Urol 2003;44:423–8. methylation status of tumour suppressor genes for have been linked to the response to BCG. However, it molecule SNPs predictive of BCG immunotherapy 5. Jackson AM, Alexandroff AB, Kelly RW, et al. Changes in predicting bacillus Calmette-Guerin response in patients should be noted that these risk factors are not unique outcome10. However, only two SNPs from the panel urinary cytokines and soluble intercellular adhesion with T1G3 high-risk bladder tumours. Eur Urol 2011; 60: to BCG but are associated with unfavorable NMIBC (IL17A rs2275913 and IL18R1 rs3771171) correlated to molecule-1 (ICAM-1) in bladder cancer patients after 131–40. outcomes as well. Therefore, molecular diagnostic BCG treatment response in an Asian population; as bacillus Calmette-Guerin (BCG) immunotherapy. Clin Exp tools have also been investigated, and may have a allele distributions were different between the two Immunol 1995; 99:369–75. Editorial Note: Due to space constraints the role to anticipate BCG immunotherapy failure1. population. This was also observed in NRAMP1 SNP 6. Renate Pichler, Josef Fritz, Claudia Zavadil, et al. reference list has been shortened. Interested association studies and deviation between the Tumor-infiltrating immune cell subpopulations influence readers can email at [email protected] Detection for chromosomal aberration using urinary Canadian and Asian reports may be due to allele the oncologic outcome after intravesical Bacillus to request for the full list. fluorescent in situ hybridization (FISH) shows potential distribution differences of the SNPs analyzed11,8. Calmette-Guérin therapy in bladder cancer. Oncotarget as a predictive tool of BCG failure. During BCG therapy, 2016; 7(26):39916-39930. Sunday 16 March patients with positive FISH results after induction Thus, a better strategy may be to evaluate gene 7. Kamat AM, Briggman J, Urbauer DL, et al. Cytokine Panel 09.15-12.15: Urology Beyond Europe, Joint therapy were shown to have higher cancer recurrence transcription or function rather than SNPs. However, for Response to Intravesical Therapy (CyPRIT): nomogram Session of the European Association of Urology risk (3-5 fold) and progression risk (5-13 fold)2. this is rather difficult to do as it requires the of changes in urinary cytokine levels predicts patient (EAU) and the Federation of ASEAN Urological development of predictive assays that correlate with response to bacillus Calmette-Guerin. Eur Urol 2016; Associations (FAUA) Some studies have also attempted to associate the gene’s functional response to BCG therapy. 69:197–200. tumour antigen expression with BCG response. Furthermore, the response to BCG is complex, as it is However, correlation of a single tumour biomarker likely that many genes and proteins are involved, and with BCG response is confounded by the inherent therefore assays evaluating single proteins may be of molecular diversity of bladder cancer and the complex limited value. Although the evaluation of the global immunological cascade induced by BCG. p53, response of patient immune cells to BCG prior to Retinoblastoma protein, Survivin, B-cell lymphoma 2, therapy, using array-based technologies monitoring E-cadherin, Ezrin and Ki-67 are examples of tumour the transcriptional response or protein response to biomarkers being investigated1. BCG may be a better approach, these platforms are still quite expensive to run. The development of Patients innate immunity to mycobacterium, tested targeted arrays may reduce the cost in the future. using purified protein derivative on skin, and clinical symptoms such as fever have also been considered as Emerging therapies probable predictors, though reports have not been Newer therapies on the horizon include an adjuvanted consistent3,4. cancer vaccine (MAGE-A3), which was safely administered with standard BCG therapy in NMIBC BCG immunotherapy induces an immunologic patients, in a Phase 1 trial, and it is the first to show an response. Following BCG instillation, an increase in increase in local T cell response12. Other intravesical leukocytes in urine has been associated with better immunotherapies in Phase 2 and 3 trials, include the BCG response5. Immuno-histochemical analysis of combination of BCG and vaccines (intradermal HS-410 immune cells in tumour tissue have also been or PANVAC), genetically engineered BCG and modified correlated with response to therapy6. A panel of adenovirus as monotherapy13. cytokines (IL2, IL6, IL8, IL18, IL1ra, TRAIL, IFN-gamma, IL12p70 and TNF-alpha), detected in the urine, with a The identification of regulatory T cells and high predictive value for BCG response was also being immunosuppressive immune cells in tumour tissue validated7. Increased expression of antigen presenting has also led to the evaluation of immune checkpoint molecules, major histocompatibilty complex class I blockers (ICB) such as anti-PD-L1 and anti-PD-1. PD-L1 and II, and ICAM1, has also been linked to favorable which is the Programmed cell death-1 receptor, is therapy outcomes. However, BCG induced antitumor expressed on activated T cells and binds to its ligand REGISTER NOW immunity is multifaceted and many molecules are PD-L1. This ligand is expressed on normal cells and by linked with response to therapy. Constant monitoring binding PD-1 it limits the immune response. Join us in the spectacular city of Paris, France, for the 36th World Congress of of these molecules during BCG treatment may be Endourology, the world’s foremost meeting dedicated to minimally invasive urologic challenging. PD-L1 expression is found in some bladder tumour cells, especially the higher grade ones, thus the surgery. Assembling today’s global leaders in endourology, WCE 2018 will provide Genetic variants tumour cells are able to block immune activation and unparalleled opportunities to expand your education, enhance your skills and Genetic differences between BCG therapy responders escape removal by immune cells. PD-L1 expression is exchange ideas. and non-responders is another area of research reported to increase after chemotherapy or interest. Studies have centered around genes involved immunotherapy, and thus it may be a good candidate in the mechanisms of action of BCG. Genetic variants for intervention. Another immune checkpoint blocker, such as Single Nucleotide Polymorphisms (SNP) in CTLA-4 (Cytotoxic T lymphocyte associated protein 4), Abstracts Now Open! immune response-associated genes have been also blocks T cell activation by competing with CD28 correlated to BCG response. For example, allelic for binding to B7 ligands (CD80/CD86). In normal variants in Human glutathione peroxidase 1 (hGPX1) immune processes, it serves to limit immune and Natural resistance-associated macrophage responses but in cancer it limits T cell activation. The Learn more and submit your abstract at protein 1 (NRAMP1) has been associated with bladder PD-1 and CTLA-4 pathways do not overlap. Systemic cancer recurrence after BCG immunotherapy8. ICB therapy with atezolizumab and durvalumab www.WCE2018.com NRAMP1 plays an essential role in host-mediated (anti–PD-L1 antibodies) and pembrolizumab macrophage defense against intracellular (anti–PD-1 antibodies) are being evaluated in ongoing mycobacterial infection. The NRAMP1 promoter phase 2 monotherapy studies. Both are associated variant rs34448891 allele 3 was also found to be with lower immune-related adverse events compared associated with higher progression risk (p=0.014) to systemic anti-CTLA4. Thus, anti-PD-L1 and (unpublished data). Vitamin D is known to be anti-PD-1 therapies may provide additional treatment important in macrophage-mediated mycobacterium options for BCG-unresponsive and relapsing NMIBC tuberculosis eradication. Two SNPs in the vitamin D patients.

Saturday, 17 March 2018 EUT Congress News 25 Robotic radical cystectomy Surgical hints, lymph node dissection and intracorporeal diversion

Dr. Alejandro R. Surgical technique isolated by the use of an Endo-GIA stapler. The Rodriguez Port placement starts with a 2 cm longitudinal restoration of bowel continuity is performed with a Chief, Urology and incision, 5 cm above the umbilicus. Through this stapled side-to-side ileoileal anastomosis. We use a Urology Oncology incision the peritoneal cavity is opened and a 12 mm 60 mm and an additional 45 mm Endo-Gia stapler Director, Robotics balloon trocar is introduced. After pneumoperitoneum for the side-to-side ileoileal anastomosis. Another, and Minimally is achieved at a maximum pressure of 15 mmHg, at 60 mm Endo –GIA stapler is used transversally, to Invasive Surgery high flow, a 12 mm (0 or 30 degrees) hand-held close the open ends of the ileal limbs. The Samaritan Medical robotic camera is inserted, to assist in placing the mesenteric trap defect is closed using running 3-0 Center other trocars under direct vision. Three 8 mm robotic vicryl sutures. New York (US) metallic ports, one 12 mm assistant port, and one 15 mm assistant port (for insertion of endoscopic We then put into stretch both ureters by pulling on articulating staplers) are placed. (See Figure 1) the sutures attached to the hem-o-loks clipped to Radical cystectomy remains a procedure associated both ureters, using the Prograsp forceps. Once the with high morbidity. A recent contemporary study Radical cystectomy and bilateral extended pelvic ureters are lined up one next to the other, a 3 cm that analyzed 6,510 patients over a six-year period lymph node dissections longitudinal incision is made along the anterior (2010-2015), reported that 31.5% of patients For the oncological part of the surgery, which includes aspect of the distal ends (spatulation), to create a experienced a complication and 40.7% of patients the radical cystectomy and the bilateral extended wide anastomosis in a Wallace fashion. This is done required a blood transfusion. The length of stay pelvic lymph node dissection, it is important to using a 4-0 monocryl running suture. Once this is decreased over time from 10.6 days in 2010 to 9.2 identify three avascular spaces: the periureteral space, performed we cut the staple line of the proximal end days in 2015 (p<0.01), however readmissions the lateral pelvic space and the anterior rectal space. of the ileal conduit segment selected to perform the increased slightly over the time period to 21.4% in Once these spaces are identified: 1. The ureters are ureteral ileal anastomosis in a tension-free manner. 2015 (p<0.01)1. clipped (Hem-o-lok with vicryl suture attached to First the posterior anastomosis is performed starting them) accordingly, to aid in an exact estimated blood proximal at the spatulation site of the right ureter. The use of the robotic-assisted approach, for the loss count; dilating them for an easier reconstruction Running 4-0 monocryl sutures are used for the surgical management of bladder cancer and of the urinary tract afterwards; and preventing anastomosis. A Prograsp stabilizes the Wallace Plate reconstruction of a urinary diversion, has increased possible cancer cell seeding, specially if ureters are and facilitates the anastomosis in a tension- free since its description in 20032. Contemporary studies stented prior to surgery. 2. The vascular pedicles can manner. (Figure 5) on radical cystectomy series, report that 28.9% to be identified to either staple them with endovascular 39.4% of patients underwent a robotic assisted articulating staplers, or dissect them and secure them approach3,4. Since more than five years ago, in our with hem-o-loks selectively (when preserving institution, as well as in others, 100% of the radical neurovascular structures). 3. The rectum can be cystectomies and urinary diversions are performed dissected away from the posterior bladder wall, the using the robotic assisted technique5. Multiple posterior Denonvillier’s fascia can be opened, and the Figure 4 A, B, C: Right Extended Pelvic Lymphadenectomy studies, including randomized controlled trials, rectum can be dissected away from the prostate from have demonstrated that Robotic assisted radical base to apex under direct vision. cystectomy (RARC) is comparable to open radical intraabdominal pressures, for an easier dissection of cystectomy (ORC) with regards to: surgical margins, Once the posterior dissection is completed, the the lymphatic tissue at this level. Finally, the nodal number of lymph nodes resected, five-year anterior exposure and apical dissection are performed packages from each side are placed in separate cancer-specific and overall survival, as well as, by: 1. Incising the median and medial umbilical Endocatch bags and removed at the end of the local and distant recurrences6-12. Although, RARC ligaments to release the bladder from the anterior procedure. Figure 5: Wallace type of ureteral ileal anastomosis may take longer (specially during the learning abdominal wall. 2. Opening of the endopelvic fascia (Intracorporeal Ileal Conduit) curve), it has demonstrated: less estimated blood bilaterally and suture ligation of the deep dorsal Intracorporeal urinary diversion (Abdominal wall loss, less risk of blood transfusions, and shorter venous complex. Once the proximal membranous and orthotopic) length of stay6,13,14. urethra is skeletonized, the urethral catheter is The reconstruction part of the surgery starts by the Prior to completing the anterior layer of the removed and a Hem-o-lok clip is applied just distal to retroperitoneal transfer of the left ureter to the right ureteroileal anastomosis, ureteral stents (6 French It is widely known that most postoperative the apex to prevent urine spillage. (Figure 2) After side. The posterior attachments (mesocolon) of the single pigtail ureteral stents inserted over a 0.035 in. complications following radical cystectomy arise from incision of the urethra the specimen is placed in a colon are freed beginning at the sacral promontory in guide wire) are introduced through the distal end of the urinary diversion reconstruction. Complications retrieval bag and removed from the pelvic cavity. the presacral space providing an unobstructed the isolated ileal loop. They are introduced through (30 and 90 day; Grade 3-5) have been comparable passage or tunnel. The sigmoid colon is retracted the assistant port and guided into the ileal conduit with both approaches (Open versus Robotic). superiorly and anteriorly, and a blunt tip grasper is using a fenestrated grasping forceps, delivered near However, all the randomized control trials reported, passed under the surface of the mobilized colon at the butt end of the loop at the prospective have compared ORC to RARC with extracorporeal the level of the sacral promontory. The suture tied to ureteroileal anastomotic site and then advanced into urinary diversion15. the hem-o-lock attached to the distal ureter is the ureters. Then the ureteroileal anastomosis is grasped and passed underneath the sigmoid loop and completed using 4-0 monocryl running sutures. The Intracorporeal urinary diversion reconstruction may brought to the contralateral side. Pulling on the distal end of the ileal conduit loop is delivered improve complications rates, and shorten even suture transposes left ureter retroperitoneally from directly through the anterior abdominal wall through more the length of stay. Performing a diversion left to right. Care is taken not to twist the ureter nor to the 8 mm port preselected stoma site. The robotic intracorporeally may influence gastrointestinal cause kinking. arm is undocked and a grasping forceps is brought complication rates by reducing bowel manipulation, through that trocar and the distal end is grasped. A mobilization and exposure. A large retrospective For an abdominal wall diversion such as an ileal lunar incision is made around the trocar and the series demonstrated that intracorporeal urinary Figure 2: Urethra dissected and clipped conduit, the bowel including the cecum, ileocecal fascia is incised in the form of a cross, as far as that diversions reduce gastrointestinal (23% to 10%; junction, and ileum is identified. A 20 cm ileal the opening allows a two-finger dilation of the p<0.001) and infection related complications (18% loop segment is isolated about 15 cm proximal to abdominal wall musculature. The conduit end is to 10%; p=0.035); as well as, 30-day (15% to 5%; Once the cystectomy specimen is moved away from the ileocecal valve by placing marking sutures (3-0 delivered. Then a rose bud technique is performed p<0.001), and 90-day readmission (19% to 12%; p= the pelvic cavity, adequate space is available for a Silk on SH needle for the distal end of the ileal to mature the stoma. A 15 JP drain to bulb suction is 0.016)16. bilateral extended lymph node dissection. We prefer segment and 3-0 vicryl on an SH needle for the placed near the ileal-ureteral anastomosis to help doing the lymphadenectomy after the radical proximal end of the ileal segment, where the detect urinary drainage, through the right lateral 8 Since more than five years ago, in our institution, cystectomy. In general, the boundaries of lymph node ureteral intestinal anastomosis is going to be mm metallic port. we perform a pure robotic-assisted radical dissection are well defined in Table 1 (Figure 3 (a,b) done). The length of the bowel is determined by cystectomy with intracorporeal urinary diversion and 4 (a,b,c)). Lymphatics are secured with clips. running the bowel and placing an umbilical tape Intracorporeal orthotopic neobladder (abdominal wall or orthotopic). There is a need for Occasionally, diminishing the pneumoperitoneal cut to 15 cm. For the creation of an intracorporeal neobladder, our the new generation of robotic surgeons to pressures down to 10 mmHg may help in identifying preference is to perform a neobladder with great familiarize themselves with anatomical landmarks, the iliac vein, which is usually flat due to Care is taken to maintain good vascularity of the capacity and proven functional results. Since more to prevent complications related to the approach of isolated bowel segment by visual inspection of the than five years ago, we have performed a “W” type the pelvis, for the ablative oncological part of the mesentery, as well as transillumination to help ileal (60 cm) neobladder described by Hautmann procedure such as the extirpation of bladder cancer identify the mesenteric vessels. In some cases, we with an additional isoperistaltic 10 cm chimney on and lymph node dissection. Finally, diffusion of have used also intravenous indocyanine green (ICG) the left side of the neobladder. This consists of a surgical hints for the creation of intracorporeal to identify major mesenteric vessels. Once the 20 cm total of 70 cm of ileum used. The left ureter is urinary diversions is necessary to prevent of ileal segment is identified, and the major transposed retroperitoneally underneath the complications related to the fully intracorporeal mesenteric vessels visualized, the segment is sigmoid colon, as describe above, from left to right. reconstruction of the urinary tract.

Lymph node chain Boundaries of lymph node dissection Proximal - Distal Medial - Lateral External lliac (1) Bifurcation of common iliac artery - pelvic floor - midline of external iliac artery - genitofemoral nerve Obturator (2) Bifurcation of common iliac artery - pelvic floor - obturator nerve - midline of external iliac artery Deep Obturator / Origin of obturator nerve - pelvic floor - bladder wall Hypogastric (3) - pelvic side wall including triangle (fossa) of Marcille Common illiac (4) Aortic bifurcation - Origin of internal and external iliac artery - midline of common iliac artery - genitofemoral nerve Presacral (5) Triangle between midline of the common iliac arteries - bifurcation of internal and external arteries, dorsal border is sacrum and medial skeletonization of internal iliac vessels Figure 1: Trocar Positioning Figure 3 A, B: Left Extended Pelvic Lymphadenectomy Table 1: Boundaries of Extended Pelvic Lymph Node Disection

26 EUT Congress News Saturday, 17 March 2018 opening of the two first limbs, a 2-0 single needle french single J stent is inserted through the assistant barbed absorbable suture (V-loc) is used to close port and passed into the ureter and into the the posterior wall of the two opened limbs, in a isoperistaltic limb, into the neobladder. Then both running fashion. Once this is finished we continue stents are passed through the anterior bladder wall opening the third and fourth limbs at the level of of the neobladder. A 3-0 absorbable stich is place to the antimesenteric border of the ileum. We then secure both stents to the anterior bladder wall. close the posterior wall again of the neobladder Using a Carter Thompson Device passed with a running 2-0 V-loc suture, in an organized percutanously, both stents are grabbed and fashion. A total of three lines of continuos sutures exterioriated through the abdominal wall. The stents are used to finish closing the posterior wall of the are secure to the skin with 3-0 nylon stiches. A Figure 6: Intracorporeal “W” neobladder presentation and neobladder. (Figure 7 A,B) urostomy bag is placed to contain the urine drained stabilization through the stents. During all this time, the ileum is stretched and stabilized, facilitating the opening and closure of the The anterior neobladder wall is closed completely The selection of the ileal segment to be utilized is posterior wall of the “W” neobladder. Prior to cutting with a 2-0 V loc continuous suture. We then remove started by placing a 3-0 silk on an SH needle on the both traction sutures and passing the urethral the 15 mm assistant port and close the port opening ileum, at least 15 cm away from the ileo-cecal valve. neobladder neck sutures, a posterior reconstruction of from inside using a 2-0 V loc in a running fashion, With an umbilical tape cut to 15 cm, measurements the Denonvillier’s Fascia is performed to bring the to prevent a port hernia. After taking out the of the first, second, third and fourth limbs, are urethral stump further into the pelvis (an extra Prograsp and undocking the Fourth arm, a 15 round performed and secured by placing 3-0 vicryl stiches lengthening of the urethral stump of at least 1-2 cm JP drain is passed through the port and placed on on SH needles for identification of each limb of the more into the pelvis). This reconstruction is performed top of the fully intracorporeally created neobladder. “W”. At the end of the fourth limb we measure an with a 3-0 V-loc continuous suture. Figure 8 A, B: Urethral Neobladder Neck Anastomosis, Anterior After irrigating the abdominal cavity, and securing additional 10 cm for the isoperistaltic limb, and Wall Closure and Final Neobladder hemostasis, all robotic instruments are removed place a 3-0 colored vicryl stitch. Once this is performed, a 2-0 double needle barbed and the robot is completely undocked. All specimens absorbable suture (Quill), is passed through the are removed in separate Endocatch bags, by We then perform resection and isolation of the 70 cm assistant port. We then pass both needles from extending the 2 cm supraumbilical vertical midline ileal segment, as described for the intracorporeal outside in, at the level of the neobladder flap incision to a total of 5 cm. ileal conduit technique. After performing a side to created on the right side of the “W”. Once this is side ileal reanastomosis using Endo-GIA staplers, the done, the percutaneous 0 silk stitches served for Anatomical knowledge “W” neobladder is stabilized. The stabilization of the traction are cut. This will make the neobladder fall Robotic assisted radical cystectomy with “W” neobladder is facilitated by passing two 0 silk flat into the pelvis on top of the rectum. A urethral intracorporeal urinary diversion is the present in straight keith needles suprapubically percutaneously, neobladder neck anastomosis is performed from our institution. Strict knowledge of pelvic and passing them through and through both vertexes outside-in, into the neobladder and from inside-out, anatomy, and adherence to oncological principles, of the “W”. This keeps the “W” shaped ileum into the urethral stump. Both needles are passed enhances oncological results. Intracorporeal stretched toward the pelvis. With the third arm, and twice in the neobladder and the urethra, prior to reconstruction of the urinary tract, following strict using a Prograsp, the vicryl stiches placed on the pulling them bilaterally and approximating the proven open urinary diversion principles, may “W” are also grabbed and retracted toward the head. neobladder neck to the urethra. Once this is improve the morbidity of this complex procedure This perfect stabilization and stretching of the “W” performed, the anastomosis is completed and prior even further. shaped ileum, facilitates the organized opening of to closing the neobladder neck anteriorly, a 20 the ileum in the antimesenteric border. (Figure 6) french foley catheter is inserted through the urethra. Editorial Note: Due to space constraints, the (Figure 8 A,B) reference list can be made available to interested The ileum is always opened in a standard organized readers upon request by sending an email to: fashion starting with the right limb of the “W”, and After closing the bladder neck with the Quill stich, [email protected] proceeding to the second limb. At the vertex of the the anterior wall of the neobladder is closed with a “W”, the incision in the antimesenteric boarder (first 2-0 V-loc in a running fashion. Prior to closing Friday 16 March limb) is brought close to the mesentery, creating a completely the anterior neobladder wall, a Bricker 08.45-12.15: Urology Beyond Europe, Joint nice wide flap of ileum (2-3 cm in length without type of ureteral intestinal anastomosis is performed Session of the European Association of Urology stretch and 6 cm wide without stretch) that will be in the 10 cm isoperistaltic limb on the left side of the (EAU) and the Confederación Americana de the area where the urethral neobladder neck Figure 7 A, B: Opening and Suturing of the Posterior Wall of “W” neobladder that was not open. Prior to Urología (CAU) anastomosis will be done. After finishing the the Neobladder finishing each ureteral intestinal anastomosis, a 6

EDAP TMS Booth# G66 Reviewers New EAU guidelines Live Demos Members, available online! don’t forget by the Experts Pocket App free for EAU members to pick up your Congress Gift!

for Prostate HIFU Cancer Remember to Everyday European 11:00 AM & 2:00 PM pick up your Association copy at the of Urology EAU Booth H69 for Urinary Stones ESWL Guidelines For this relief, much thanks! Saturday 17th March 2018 edition 10:30 AM & 3:00 PM Peeing in art At the 33rd Annual EAU Congress, EAU18 in Copenhagen, Booth# G66 EAU members can look forward to a new publication by Dr. Johan Mattelaer. For this relief, much thanks! explores the depiction of urination in art, both classical and contemporary. It is a beautifully illustrated coffee table book that celebrates our ﬁ eld and offers unique insights.

The book can be picked up at the EAU Booth in the Exhibition,

with the appropriate entitlement and on a fi rst come, fi rst 22-01-18 11:00 served basis.

Omslag GL 2018.indd 1

Saturday, 17 March 2018 EUT Congress News 27 Best Abstracts: First prize winners British study bags oncology prize while a multi-centre study from France tops non-oncology

Editorial Note: We are re-printing here the unedited rules for efficacy and inefficacy. Secondary endpoints Authors: A. Chebbi, A. Giwerc, Results and original prize-winning abstracts submitted to included metastasis-free survival, overall survival, B. Peyronnet, L. Freton, J. Olivier, Among a total of 1500 kidney trauma over the studied this year’s congress. Congratulations to all the toxicity (CTCAE v4) and patient reported quality of life Q. Langouet, M. Ruggiero, period 268 patients met the inclusion criteria. The authors and researchers for their innovative work, (assessed by EORTC QLQ-C30 and EQ5D). I. Dominique, C. Millet, S. Bergerat, median age was 25 years and 158 (79%) patients insights and contributions to urology. P. Panayotopoulos, R. Betari, were male. Clinicians performed an ED with ureteric Results X. Matillon, T. Caes, P. Patard, stent insertion for 69 patients (26%). A persistent UE First Prize for the Best Abstract (Oncology) Between 31st May 2012 and 5th September 2017, 248 A. Chebbi N. Szabla, N. Brichart, L. Sabourin, was found in 50 patients (36%) of the CM on the Abstract No: AM18-0618 patients were randomized (123 surveillance; 125 K. Guleryuz, C. Dariane, C. Lebacle, repeat CT in mean delay of 6 days. This persistent leak Results of POUT - A phase III randomised trial of chemotherapy) at 57 UK centres. In October 2017, the J. Rizk, A. Gryn, F. Madec, M. Hutin, B. Pradere, required a delayed ureteric stent insertion in 23 peri-operative chemotherapy versus surveillance in independent trial oversight committees recommended C. Pfister, G. Fiard, F. Nouhaud (Rouen, Rennes, Lille, patients (17%). The mean length of staywas longer upper tract urothelial cancer (UTUC) POUT close to recruitment as data collected thus far Tours, Paris, Lyon, Clermont-Ferrand, Strasbourg, after ED 21 days vs. 14 days after CM (p=0,03). There (data snapshot 5th September 2017) met the early Angers, Amiens, Toulouse, Caen, Nantes, Montpellier, was no difference in complications rate and death Authors: A. Birtle, M. Johnson, stopping rule for efficacy. At the time of interim Grenoble, France) related to the trauma between the 2 groups. R. Kockelbergh, F. Keeley, J. Catto, analysis, median follow-up was 17.6 months (IQR R. Bryan, J. Chester, R. Jones, 7.5-33.6). Patients had median age 69 years (range Introduction & Objectives Conclusions M. Hill, J. Donovan, A. French, 36-88), 30% pT2, 65% pT3; 91% pN0. Grade ≥3 Management of non-penetrating renal trauma (NPRT) Our results suggest that CM should be considered for C. Harris, T. Powles, R. Todd, toxicities were reported in 60% chemotherapy associated with urinary tract rupture (AAST Grade the management of renal trauma associated with L. Tregellas, C. Wilson, A. Winter- patients and 24% surveillance patients. During the IV-V) is not clearly codified regarding the usefulness urinary extravasation at the initial CT-assessment. CM A. Birtle bottom, R. Lewis, E. Hall (Preston, treatment period the most common grade ≥3 [≥4] of upper tract drainage with stent insertion. The aim was associated with good outcomes as 83% of the Newcastle upon Tyne, Leicester, toxicities in chemotherapy patients were neutropenia of this study was to compare the outcomes of an early patients didn’t required any drainage of their upper Bristol, Sheffield, Birmingham, Cardiff, Glasgow, 29% [5%] (vs. 0% surveillance) and upper urinary tract drainage (ED) to a conservative tract and the urinary extravasation at repeat CT was London, Southend, Chinnor, United Kingdom) thrombocytopenia 7% [6%] (vs. 0%). 47/123 management (CM) after a NPRT with a urinary still present for 36% of the patients only. Initial (surveillance) and 29/125 (chemotherapy) DFS events extravasation (UE) at initial CT-scan assessment. clinical monitoring and repeat CT-scan to re-assess Introduction & Objectives were reported; unadjusted HR = 0.47 (95% CI: 0.29, the urine leak might be useful and less invasive than The role of post nephro-ureterectomy treatment for 0.74) in favour of chemotherapy (log-rank p= 0.0009). Materials & Methods a systematic ED. UTUC is unclear. POUT (CRUK/11/027; NCT01993979) is Two year DFS was 51% for surveillance (95% CI: 39, A multicenter retrospective national study a UK led trial that addresses whether adjuvant 61) and 70% for chemotherapy (95% CI: 58, 79). was conducted, including all patients chemotherapy improves disease free survival (DFS) for Metastasis-free survival also favoured chemotherapy: treated for renal trauma in 16 centers Table: Results after NPRT with urinary extravasation patients with histologically confirmed pT2-T4 N0-3 HR = 0.49 (95% CI: 0.30, 0.79, p=0.003). from 2005 to 2015. Patients who had M0 UTUC. a UE at the initial CT-scan assessment Conclusions delayed phase were considered for Materials & Methods Adjuvant chemotherapy is tolerable and improved inclusion. Penetrating traumas, Patients (maximum n=345), WHO performance status metastasis-free survival in UTUC. Recruitment to the hemodynamically unstable patients 0-1, ≤90 days post NU were randomised (1:1) to 4 POUT trial was terminated early because of efficacy and those who were initially treated cycles of gemcitabine-cisplatin (gemcitabine- favouring the chemotherapy arm; follow up for overall with nephrectomy were excluded. carboplatin if GFR 30-49ml/min) or surveillance with survival continues. POUT is the largest randomised Patients were divided into 2 groups: chemotherapy given on recurrence if required. trial in UTUC and its results support the use of ED defined by drainage of upper Patients had 6 monthly cross sectional imaging and adjuvant chemotherapy as a new standard of care. urinary tract of the injured kidney cystoscopy for the first 2 years, then annually to 5 within the 48 hours following the years. Toxicity was assessed by CTCAE v4. The primary First Prize for the Best Abstract (Non-Oncology) admission and CM. The persistence of endpoint was DFS. The trial was powered to detect a Abstract No: AM18-3773 UE at repeat CT-scan, the need for hazard ratio (HR) of 0.65 (i.e. improvement in 3 year Is systematic early drainage relevant to treat urinary delayed drainage, length of stay, DFS from 40% to 55%; 2-sided alpha=5%, 80% tract rupture in non-penetrating renal trauma? Results complications rate and specific death power) with Peto-Haybittle (p<0.001) early stopping from a multicenter study related to the trauma were analyzed.

STEPS Interactive, Insightful and Sessions To Evaluate ProgresS in the management of Independent Education urological cancers Learning from Experts in Onco-Urology

Applications now open! Visit Ipsen booth E15 during EAU18 to learn more

What is STEPS? STEPS, or “Sessions To Evaluate ProgresS in the management of To date, 20 different internationally recognised experts, urological cancers”, is a programme specifi cally designed for recently supported by the ESOU Board, have inspired 138 Next event: specialised onco-urologists who want to learn directly from world- fellows from 29 countries – and our objective is to Meet-the-Expert Session th leading experts in bladder, prostate, renal and testicular cancers. continue supporting STEPS to help improve the during the 16 Meeting The CME-accredited programme is a fundamental part of the EAU/ management of all patients with urological cancers. of the EAU Section of ESOU strategic partnership with Ipsen. It is founded on our shared Oncological Urology (ESOU) th commitment to the education of young urologists. Who should apply? Saturday 19 January 2019 Recently specialised clinicians with a fi rm interest in Prague, Czech Republic Bringing together a multinational group of medical professionals the management of urological cancers, who: across several areas of expertise, and with different experiences, - Can demonstrate support from their Head of allows the fellows to see a variety of new treatment possibilities. Department It can highlight the pitfalls and solutions provided by diverse - Are keen to participate in ESOU and EAU approaches. It also opens the door to creating international ties programs among medical practitioners, and a networking opportunity that can prove invaluable for the careers of young clinicians. - Understand and speak English fl uently

“STEPS connects younger urologists from different countries “Within STEPS I really like the enthusiasm of the – it’s very interactive with lots of new information and data delegates and the interaction I can have with them discussed” STEPS fellow 2018 as an expert” Peter Mulders, STEPS mentor 2018

Find out more about STEPS from the ESOU website: http://uroweb.org/section/esou/information/

TRI-ALL-000297 ESOU is an independent 3rd party meeting. Travel, accommodation, registration and subsistence costs are supported by Ipsen.

T115 STEPS Advert 270 x 194.3.indd 1 16/02/2018 09:27 28 EUT Congress News Saturday, 17 March 2018 ESU Masterclasses: Designed and aimed to educate Participants’ feedback is crucial to continually improve the masterclass format

Dr. Joan Palou of top experts who provide the best and the latest Benefits for the participants Chairman, European updates in their respective fields. Completion of an ESU Masterclass means improved School of Urology proficiency of participants in terms of practical Dept. of Urology ESU Masterclasses diagnosis, specific techniques, decision-making and Fundació Puigvert At present, there are seven Masterclasses which are management. Barcelona (ES) as follows: The feedback received from each Masterclass continue • ESU-ESUT Masterclass on Operative management to show overall satisfaction from participants. They of Benign Prostatic Obstruction focuses on relevant, indicated noticeable improvements with their skills minimally-invasive alternatives for BPO treatment; and a boost in their clinical practice after incorporating take-home messages and concepts. • ESU Masterclass on Female and Functional Progress is inevitable; what we know now as Reconstructive Urology covers the management Up-to-date, practical tips and tricks they have urologists in terms of research, technologies and of functional disorders such as lower urinary tract acquired from the Masterclasses greatly benefitted procedures will eventually need an upgrade. We diseases, and other diseases that affect the pelvic their patients. need to grow alongside this advancement, for our floor and related organs; patients and for our practice. Hence, the inception of A pre-test and post-test are implemented to boost the European School of Urology (ESU). • ESU-ESUT-ESUI Masterclass on Focal therapy for quality and to evaluate the efficacy of the localised prostate cancer provides a masterclasses and the faculty (what works and what ESU’s primary goal is to increase what we know and comprehensive review of the rationale for FT and A Hands-on Training session at the BPO Masterclass needs improvement), and to gauge the knowledge of to broaden our skills through various activities the modalities of patients selection; participants designed to meet our educational needs while taking our challenging schedules into account. The • ESU-ESUT Masterclass on Lasers in Urology offers • ESU-ESOU Masterclass on Non-Muscle-Invasive Plans high-level ESU Masterclasses are one of the ESU’s the mastery of basic concepts of each laser Bladder Cancer delivers modern techniques of There is a steady increase in the demand for ESU most prominent activities. treatment, identification of suitable candidates transurethral surgery from en-bloc resection, new Masterclasses since its establishment and up to this per approach, and management of complications; imaging technologies to new generation day. This is truly encouraging. Through these Why choose the masterclass format? equipment; Masterclasses, participants are given the opportunity Although ESU Courses offer frontline lectures, the to access the best resources in urology. The ESU aims ESU Masterclasses, in collaboration with the EAU • ESU-Weill Cornell Masterclass in General urology to expand starting next year the number of topics to sections of the EAU, are created to be more has a three-year rotation programme. This year, meet increasing demand. in-depth. These masterclasses cover urolithiasis, the masterclass will focus on stone management, non-muscle-invasive bladder cancer, to focal urothelial cancer update, and paediatric urology; therapy, among other topics. The ESU Masterclass format is a consolidation of cutting-edge lectures, • ESU-ESUT Masterclass on Urolithiasis is typical or sometimes challenging clinical cases, and comprised of theoretical courses on stone informative semi-live and live surgeries. The disease: pathophysiology, diagnosis and programme also feature riveting discussions and conservative treatment of lithiasis, and hands-on demonstrations. extracorporeal and interventional management;

Even the setting is conducive to learning. Each • ESU-ESTU Masterclass on Kidney Transplant is Masterclass has a defined number of participants the latest installment to the masterclass series – small enough for optimal learning for good, solid designed to offer high-level theoretical and interactions and large enough for productive Full house at the opening of the 1st ESU-ESOU Masterclass of practical training, and detailed updates on kidney brainstorming. Its commendable faculty is comprised NMIBC (Photo by Dr. Fadi Dalati) transplantation. All eyes on Prof. E. Liatsikos at the Urolithiasis Masterclass

EAU Member iee iee res res r ress Beneﬁ ts at EAU18!

EAU members are kindly invited to the Congress delegates are kindly invited to collect EAU Booth H69 in the Red Area to collect the the following complementary items: following complimentary items: EAU18 Abstracts USB EAU Extended Guidelines A USB containing all The EAU Extended Urological Guidelines edition 2018. presented abstracts during the 33rd Annual EAU EAU Pocket Guidelines Congress can be collected at The pocket version of the EAU Guidelines edition 2018. booth G01 in the Red Area.

De Historia Urologiae Europaeae Vol. 25

MINIMAL SYSTEM REQUIREMENTS EAU18 ESU CoursesWindows PC * Windows Vista / 7 / 8 / 10 DVD The EAU History Ofﬁce is presenting a special, Macintosh * OS X 10.5 and newer (Intel) Installation of Adobe Acrobat Reader to open PDF presentations.

USAGE Insert the DVD-ROM in the DVD tray of your computer. A DVD includingIf the application does not allstart automatically, please open the Explorer anniversary edition of De Historia this year, with or Finder, go to your Disc Drive and run the “ESUCOURSES2018” Application. Some information contained in this DVD may cite the use of products in a dosage, for an indication, or in a manner other than recommended. Before prescribing the product always refer to the prescribing information contributions from every past Editor. Features presentationsavailable in andyour country. course For more information: EAU Education Office PO Box 30016, 6803 AA Arnhem, The Netherlands T +31 (0)26 389 0680 materials of [email protected],the www.uroweb.org ESU BARCEA a wide range of interesting biographies, new 9 March 9 oin us! EAU EU Courses Are You Not done Watching? research and personal stories from the history of Courses given during the wwweauorg our ﬁ eld. congress can be collected at

wwwer Surgery in Motion School presents booth E11 in the Red Area. Surtd y For this relief, much thanks!

MINIMAL SYSTEM REQUIREMENTS The new publication by Dr. Johan Mattelaerew explores Windows PC * Windows Vista / 7 / 8 / 10 Macintosh * OS X 10.5 and newer (Intel) you with a selection of the best EAU18 PostersInstallation of AdobeDVD Acrobat Reader to open PDF presentations.

USAGE Insert the DVD-ROM in the DVD tray of your computer. If the application does not start automatically, please open the Explorer the depiction of urination in art, both classical and A DVD containingor Finder, go to your Disc Drive andposters run the “POSTERS2018” Application. Some information contained in this DVD may cite the use of products in a dosage, for an indication, or in a manner other than recommended. Before prescribing the product always refer to the prescribing information contemporary. It is a beautifully illustrated coffee available in your country. Live Surgeries from EAU18 presented duringFor more information: the European Association of Urology PO Box 30016, 6803 AA Arnhem, The Netherlands T +31 (0)26 389 0680, F +31 (0)26 389 0674 table book that celebrates our ﬁ eld and offers unique [email protected], www.uroweb.org BARCEA 33rd Annual EAU Congress. 9 March 9 insights. The book can be picked up at the EAU Booth oin us! EAU Posters A copy of the EAU18 wwweauorg H69 in the Exhibition with the appropriate entitlement Posters DVD is distributed

wwwer Surtd y a and on a ﬁ rst come, ﬁ rst served basis. in the congress bag. ducata rat r

Historia Urologiae Europaeae series is Europeanaddressed to all European urologists. Its aim is to make known the ideas and the work of our predecessors, and to help us understand the cur- DE HISTORIA Associationrent trends in the development of our speciality. Unfortunately, the treatises written in Sanskrit, ancient Chinese, Greek and Latin are both dif- of Urologyficult to find and difficult to understand, and should, therefore, be translated into English. The same applies to more recent books published in various languages.

GuidelinesMost of the treatises produced before the 17th century, even the legendary ones, have UROLOGIAE EUROPAEAE 25 2018 edition gaps, mistakes and inconsistencies. Modern Improve your surgical skills scientific research allows us to re-evaluate this ancient knowledge and examine it from new perspectives. The History Office of the EAU in collaboration with internationally based urologists, historians, philologists and other experts, conducts research, accumulates and shares this fascinating information in their annual publica- With top notch videos of urological procedures tion, Historia Urologiae Europaeae.

“Remember the days of old, consider the years of many generations, ask thy father, and he will shew thee; thy elders, and they will tell thee.” (Deuteronomy 32:7) By the best surgeons in the world DE HISTORIA UROLOGIAE EUROPAEAE

VOLUME 25 European Association of Urology 2018 EDITED BY PHILIP VAN KERREBROECK, DIRK SCHULTHEISS AND JOHAN MATTELAER

Omslag GL 2018.indd 1 22-01-18 11:00

Surgery in Motion School is a collaboration of surgeryinmotion-school.org

Saturday, 17 March 2018 EUT Congress News 29 Driving this growth are the positive anecdotal patient feedback and results from Asian studies which have fanned the confidence in ESWT in Asia. While ED seems to be a driving demand, many patients suffering from CPPS are also seeing good treatment responses and the cross application of ESWT for CPPS also provides the acceptance by many urology practices towards acquiring ESWT machines. For CPPS patients, Guu et al11 In Taiwan reported in their study that 27 of the 33 patients (81.82%) had a successful response to Li-ESWT, with a decrease of 3.29 and 5.97 in the VAS score and total IPSS at the three-month follow-up while Zeng et al12 in China reported that 71.1% of CPPS patients on ESWT exhibited perceptible improvement in total NIH-CPSI compared with 27.0% of the control group (P < 0.001). Over the last three years in Singapore, there has been an increase in the number of machines and the range of available models from Storz, Medispec and Dornier used for the treatment of ED, CPPS and painful bladder syndromes both in public and private institutions. In our institution we recruited 14 local patients with erectile dysfunction and assigned them to treatment with ESWT. We evaluated treatment outcomes with IIEF scores and EHS scores. Patient satisfaction based on EDITS scores were also recorded. Our results at the end of 12 sessions showed an increase in the mean IIEF scores from 11.9 to 17.3, with a p- value of 0.03. 82% of patients had improvements with IIEF scores, with 54% achieving at least a five-point increase in IIEF scores. 63% of our patients achieved treatment success with an EHS score ≥ 3, allowing for penetration during intercourse. 90% of our patients were recorded to have an increase in EDITS score from 51 to 69.7, p< 0.001. Low-intensity ESWT An Asian tsunami breaking the horizon

Dr. Colin Teo lifestyles, cardiovascular disease is slowly becoming a Dept. of Urology focus for most countries. A paper published in 2011 Khoo Teck Puat estimated the prevalence of ED in Asia varies between Hospital 9% and 73%10. Over the last few decades, taboos Singapore (SG) about sexual disorders have also been slowly eroded, leading men to be more forthcoming in seeking help for erectile dysfunction. Compared to a decade ago, urologists in Asia are starting to see more patients willing to seek treatment with ED. Within Asia however, unique challenges lie in addressing the treatment of ED with ESWT. Culturally, significant weight is placed by patients on traditional and The use of Low-intensity shockwave therapy(LiESWT) alternative treatments. Men who are frustrated by the in urology has been making waves in Asia. In the lack of efficacy with PDE5-inhibitors often turn to short span of the last few years, we see a rising acupuncture or other alternative therapies in a bid to trend in the use of LiESWT in Asia as more machines gain results. We are beginning to see a surging and available models are acquired by many urology demand and interest in ESWT in many Asian countries practice. where we see an increase in ESWT machines not just in numbers, but in the different models being used by We see an increasing confidence in patient outcomes urologists. We also see an increasing trend amongst Moving forward, the use of ESWT by urologists in Asia is likely to continue its encouraging more Asian urologists to embrace and General Practitioners with specialist interest in Men’s growth and Asian patients will enjoy greater access to ESWT. In the short span of include Extracorporeal Shockwave Therapy (ESWT) in Health seeking to provide this service to their patients. pharmaceutical method of treatment of ED which we Surg Res 2009;152:96–103. their armamentarium to manage patients with Driving this growth are the positive anecdotal patient can bring to our patients. With more studies and 5. Yoram Vardi *, Boaz Appel, Giris Jacob, Omar Massarwi, Erectile Dysfunction (ED) and Chronic Pelvic Pain feedback and results from Asian studies which have understanding in ESWT technology, we hope to see Ilan Gruenwald. Can Low-Intensity Extracorporeal Syndrome (CPPS). fanned the confidence in ESWT in Asia. improvements in outcomes with new treatment Shockwave Therapy Improve Erectile Function? A protocols that will benefit our patients with ED and 6-Month Follow-up Pilot Study in Patients with Organic Therapeutic usage of ultrasound has been around for Asian studies CPPS. The question to ask now is, ‘ Will you be caught Erectile Dysfunction. Eur Urol. 2010 Aug;58(2):243-8. many years. It was first used in the 1960s by sports Asian studies included a study In India8 in 2015 of two up in this ESWT wave as it rides across Asia?’ 6. Gruenwald I1, Appel B, Vardi Y. Low-intensity therapists and orthopaedic surgeons for soft tissue randomised groups of patients who were assigned to extracorporeal shock wave therapy--a novel effective injuries. Its effects were thought to be mediated by either 12 sessions of ESWT or placebo therapy. It References treatment for erectile dysfunction in severe ED patients direct simulation of healing and neovascularisation. showed positive results in both IIEF and EHS scores 1. Angela Notarnicola et al. The biological effects of who respond poorly to PDE5 inhibitor therapy. J Sex Med. It achieved widespread use in tendon injuries such as among its patients. Most recently, a study conducted extracorporeal shock wave therapy (eswt) on tendon 2012 Jan;9(1):259-64. plantar fascitis and patients with chronic pain1. in Guangzhou9, China compared two groups of tissue. Muscles ligaments tendons J. 2012 Jan-Mar; patients who were randomised to either ESWT 2(1):33-37. Editorial Note: Due to space constraints the Over the next few decades, the use of therapeutic treatment or usage of a vacuum erectile device (VED) 2. Nurzynska D, Di Meglio F, Castaldo C, et al. Shock waves reference list has been shortened. Interested ultrasound had spread widely. Urologists have vast also concluded that ESWT was comparable to the use activate in vitro cultured progenitors and precursors of readers can email at [email protected] experience with the use of Extra-corporeal Shockwave of a VED in the treatment of ED8. On-going research by cardiac cell lineages from the human heart. Ultrasound to request for the full list. Lithotripsy (ESWL) for the treatment of stones, which Dornier MedTech in Singapore continues to study on Med Biol 2008;34:334–42 is a prime example of the use of ultrasound for translating the tissue effects of ESWT on 1. Vacular 3. Kikuchi Y, Ito K, Ito Y, et al. Double-blind and placebo- Friday 16 March therapeutic purposes since it was first used on a healing and angiogenesis. 2. Stem cell recruitment controlled study of the effectiveness and safety of 09.15-12.15: Urology Beyond Europe; Joint human subject in February 1980. Fast forward to and activations. 3. Nerve cell activation and repair. 4. extracorporeal cardiac shock wave therapy for severe Session of the European Association of Urology today, ESWT has come a long way since it was first Immune regulation. angina pectoris. Circ J 2010;74: 589–91. (EAU) and the Federation of ASEAN Urological conceived. It all began in mid-2000s when medical 4. Wang CJ, Kuo YR, Wu RW, et al. Extracorporeal Associations (FAUA) literature from our colleagues in the cardiovascular CPPS Treatment shockwave treatment for chronic diabetic foot ulcers. J field showed during in-vitro studies that ultrasound While ED seems to be a driving demand, many could enhance the expression of vascular endothelial patients suffering from CPPS are also seeing good growth factor (VEGF) and its receptor, Flt-12. treatment responses and the cross application of ESWT for CPPS also provides the acceptance by many Another study conducted on rats showed that the urology practices towards acquiring ESWT machines. application of low energy shockwave therapy led to For CPPS patients, Guu et al11 In Taiwan reported in increased recruitment of circulating endothelial their study that 27 of the 33 patients (81.82%) had a progenitor cells, thus facilitating the onset of successful response to Li-ESWT, with a decrease of neovascularisation and angiogenesis. Further studies 3.29 and 5.97 in the VAS score and total IPSS at the 28 - 31 August among human subjects demonstrated its vascular three-month follow-up while Zeng et al12 in China effects within the myocardium as well as in patients reported that 71.1% of CPPS patients on ESWT with diabetic foot ulcers3,4. exhibited perceptible improvement in total NIH-CPSI Leading Continence compared with 27.0% of the control group (P < 0.001). Pioneering ESWT studies Research and Education It was against this background of studies that one of Singapore the pioneering studies for ESWT was performed by a Over the last three years in Singapore, there has been Call for Abstracts: 1 March - 3 April urologist with the Medispec model. Vardi et al an increase in the number of machines and the range published their study in April 2010 in the EAU journal, of available models from Storz, Medispec and Dornier thus breaking the first ground for the use of ESWT in used for the treatment of ED, CPPS and painful International Continence Society the treatment of ED5. This was a prospective trial of 20 bladder syndromes both in public and private 48th Annual Meeting men with vasculogenic ED who were treated with institutions. First started by Prof Peter Lim in Parkway ESWT. The results showed significant increases in IIEF Gleneagles Hospital, he has already treated more scores, duration of erection and penile rigidity. Ten than 200 patients on the in the region in private www.ics.org/2018 Alan J. Wein Diane Newman Chairman Co-Chairman men from the study did not require any PDE5 healthcare with the Medispec ED1000 machine . Three (phosphodiesterase 5)-inhibitor after the treatment. out of the seven public hospital institutions have since Roger R. Dmochowski Lori Birder Gruenwald and team also clearly showed the efficacy also started providing ESWT treatment to their Scienti c Co-Chair Scienti c Co-Chair of ESWT with an open label single-arm prospective patients. study of the use of ESWT with ED patients6. At the end of the study, they recorded results showing a In our institution, we recruited 14 local patients with significant increase in IIEF scores, with 72.4% of the erectile dysfunction and assigned them to treatment subjects achieving an EHS ≥3, therefore allowing for with ESWT using the Storz Duolith machine. We intercourse. Both studies subscribed to a treatment evaluated treatment outcomes with IIEF scores and protocol of two times a week for three weeks, EHS scores. Patient satisfaction based on EDITS scores followed by a repeat session after a three-week break. were also recorded. Our results at the end of 12 sessions showed an increase in the mean IIEF scores * By 2012, the two European studies had garnered keen from 11.9 to 17.3, with a p-value of 0.03. 82% of interest in ESWT as a rising novel potential and patients had improvements with IIEF scores, with non-invasive therapy for the treatment of ED with no 54% achieving at least a five-point increase in IIEF significant adverse effects. Since then, Chung et al7 scores. 63% of our patients achieved treatment from Australia subsequently published a paper in 2015 success with an EHS score ≥ 3, allowing for which recruited 30 patients who had previously tried penetration during intercourse. 90% of our patients * and failed a trial of oral PDE5-Inhibitors. 60% of the were recorded to have an increase in EDITS score from patients reported an improvement of at least 5 on their 51 to 69.7, p< 0.001. With strong positive feedback IIEF scores at the end of the study, with 67% of them from patients, we will next evaluate the Dornier Aries being satisfied with ESWT using the Storz machine. 2 machines as patients continue to benefit from ESWT In this study, the treatment protocol consisted of two in ED, CPPS and painful bladder syndromes. sessions a week for six weeks in a row. Riding the Asian Tsunami ED treatment in Asia Moving forward, the use of ESWT by urologists in Asia Over the last few decades, Asia has seen explosive is likely to continue its growth and Asian patients will growth in population and a burgeoning middle class enjoy greater access to ESWT. In the short span of less as well as aging populations in many of its affluent than 10 years since Vardi et al published their paper countries. With longer lifespans and more affluent about ESWT, we now have a non-invasive, non-

30 EUT Congress News Saturday, 17 March 2018 Shared decision-making in prostate cancer care Encouraging patient’s role in decision-making or ensuring their preferred level of involvement?

Marie-Anne Van The large majority of patients (89%, n=403) preferred These findings indicate that patients with Stam, MSc active involvement in decision-making, with the localized prostate cancer who indicated that Dept. of Urology remaining 11% (n=51) indicating a preference for they had been actively involved in treatment The Netherlands passive involvement. A similar distribution was decision-making were better informed about Cancer Institute, observed for the experienced role in decision-making their cancer and its treatment, experienced Amsterdam (NL) (active involvement=87%, n=393; versus 13% passive less uncertainty about the treatment-decision, involvement, n=61). and had less regret about the chosen treatment, compared to patients who Most patients (n=376, 83%) experienced a role in reported having experienced passive decision-making that matched their preferred role. involvement. Our results do not support However, more than half (67%) of the patients who previous studies that reported that a match preferred passive involvement reported having between decision-making preferences and Imagine you informed Jack, a patient with localized experienced active involvement (preferred less experienced role results in more favourable prostate cancer, about his treatment options. After involvement than experienced, n=34). Conversely, of health care experienced. you discussed the benefits and side-effects of the those who preferred active involvement, 11% options, Jack asks you to make the treatment experienced passive involvement (preferred more In summary, while it may seem desirable to decision. What do you do? Do you encourage Jack to involvement than experienced, n=44). tailor the patients’ role in decision-making to be actively involved in treatment decision-making? their initial preference, and particularly to a Or do you suggest a treatment to ensure that the “These findings indicate that patients preference for deferring to the advice of the patient plays the decision-making role he prefers? clinician, this does not result in less decisional with localized prostate cancer who conflict or regret. Rather, in patients with If you consult the literature about this dilemma, you indicated that they had been actively localized prostate cancer, our results support will find conflicting results. Several studies suggest a strategy of shared decision-making to that patients who prefer either more or less involved in treatment decision- increase patients’ knowledge about their involvement in decision-making than they actually making were better informed about disease and its treatment, their sense of experience have worse decision- and health-related certainty about the treatment decision, and outcomes than those for whom their preferred and their cancer and its treatment, their satisfaction with the chosen treatment. experienced role match1. But other studies concluded experienced less uncertainty about that patients who are actively engaged in their Study Members: M.A. Van Stam, MSc; A.H. decisions, regardless of role preferences, have better the treatment decision...” Pieterse, PhD; H.G. Van Der Poel, PhD, M.D.; care experiences2. J.L.H.R. Bosch, PhD, M.D.; C.N. Tillier, MANP; Active involvement was associated significantly with S. Horenblas, PhD, M.D.; N.K. Aaronson, PhD To examine which of these strategies resulted in the more prostate cancer (PC) knowledge (Cohen’s most positive outcomes in a sample of patients with d=0.30), less decisional conflict (d=0.52), and less References Saturday, 17 March localized prostate cancer, we performed a prospective, decisional regret (d=0.34). Role concordance was 1. Brom L, Hopmans W, Pasman HRW, Timmermans DR, 14.15-15.45: EAUN Thematic Session 5: Shared multi-centre, observational study. We investigated not associated significantly with PC knowledge or Widdershoven GA, Onwuteaka-Philipsen BD. Congruence decision making: Putting patients at the heart of whether active involvement in decision-making decisional regret. However, we did observe an between patients’ preferred and perceived participation urology care, Green Area Room 11 (Level 1) regardless of role preferences, or concordance between association with decisional conflict (d=0.41), in medical decision-making: a review of the literature. Friday, 16 March 2018, 10:45 - 12:15 preferred and experienced role is the strongest indicating that patients who preferred more BMC Med Inform Decis Mak. 2014;14(1):25. Poster session 06: AM18-2341: “Encouraging predictor of more favourable patient-reported involvement than they experienced had more doi:10.1186/1472-6947-14-25. every patient to be actively involved in outcomes. About 450 patients with localized prostate decisional conflict when compared to those who 2. Kashaf MS, McGill E. Does Shared Decision Making in decision-making, or ensuring patients’ preferred cancer answered questions about their preferred role in initially preferred less involvement or those who Cancer Treatment Improve Quality of Life? A Systematic level of involvement” decision-making (before treatment) and about the role experienced a match between their preferred and Literature Review. Med Decis Mak. 2015;35(8):1037-1048. Room: Blue Area, Room 5 (Level 0) they experienced (three months after treatment). experienced role. doi:10.1177/0272989X15598529. Platinum Picture Perfect

Please come to the European Urology booth #C3-C29 and have your Platinum Postcard created and posted online.

Daily from 10.00 to 18.00

europeanurology.com eufocus.europeanurology.com europeanurology.com/euoncology

Saturday, 17 March 2018 EUT Congress News 31 THE AIS CHANNEL: PHYSICIAN EDUCATION ANYWHERE, ANYTIME.

Boston Scientific is pleased to announce a new partnership with the Advances in Surgery (AIS) Channel, the new online platform with live interaction for surgical education. AIS programming shares the latest surgical techniques from leading surgeons with professionals in the scientific community. Content is complimentary, available on any Internet-enabled device, with the goal of bringing accessible surgical education to everyone.

Visit Boston Scientific booth #F15 at EAU to experience the first AIS Channel Urology transmissions:

Penile Prosthesis Implantation GreenLight™ Enucleation Saturday 17 March 16:00 | Live moderated pre-recorded case Sunday 18 March, 10:00 and 15:00 Monday 19 March 10:00 | Pre-recorded case Live moderated pre-recorded case by Dr Ignacio Moncada (Madrid) by Dr Fernando Gómez-Sancha (Madrid)

All cited trademarks are the property of their respective owners. CAUTION: The law restricts these devices to sale by or on the order of a physician. Indications, contraindications, warnings and instructions for use can be found in the product labelling supplied with each device. Information for the use only in countries with applicable health authority product registrations. This material is not for use in the U.S., France and Japan. © 2018 Boston Scientific Corporation or its affiliates. All rights reserved. UROPH-530801-AA FEB2018 www.bostonscientific.eu

32 EUT Congress News Saturday, 17 March 2018

FV3_Ad-1_BUR050818_EAU_adverts_295x420mm.indd 1 02.03.18 15:11