BJUIBJU INTERNATIONAL NEWS ANDU INFORMATIONroscan RESOURCE FOR THE INTERNATIONAL UROLOGY COMMUNITY By Kevin D. Blanchet Cycling Through the Last Eden Madagascar trip raises money for The Urology Foundation

Imagine waking up at 5 am each morning enshrouded in a frosty mist outside. By mid- afternoon, you are sweating buckets, pedaling furiously as the temperature climbs and the humidity sets in. By dusk, jackets, a hot toddy and a warm bed are needed as the night chills down. Now, try doing this for five straight days. Such was the adventure of 22 men and women, including six urologists, who embarked on The Urology Foundation’s (TUF) Cycle Madagascar last Riders looking set for the Tour de France. Left to right: John September. Organised every Fitzpatrick, Krishna Patil, Roger Kirby, Alex Cooke, Roger Plail and year by Roger Kirby of The Peter Rimington. Prostate Centre in London, UK, this time the charity ride nation of Madagascar, located (Jay) Smith, Jr. from Nashville, took participants to the island off the southeastern coast of USA. The group also included Africa in the Indian Ocean. The actor Christian Cooke, costar ride raised £56 000 for TUF. In of Cemetery Junction, and his Must Reads at BJUI.org 2009, Roger took the group to brother Alex, an actors’ agent, Malawi, another African nation EMI Records producer Avery For a limited time, read and download for free December’s best (See the December 2009 issue Duff, prostate cancer survivors, papers as selected by BJUI’s editor and reviewers at www.bjui.org. of UroScan to read about the family members and friends. This issue’s selections are: Malawi trip). “This was a similar Wiley-Blackwell employees Gavin • Successful control of schistosomiasis and the changing trip but in many ways much Sharrock, publisher of BJUI, and epidemiology of bladder cancer in Egypt better”, he says. “Madagascar Chris Graf, editorial director, also • Overall survival in patients with metastatic renal cell carcinoma was a more interesting place rose to the challenge. Possibly initially treated with bevacizumab plus interferon-±2a and with its fascinating flora and the most inspirational member subsequent therapy with TKIs: a retrospective analysis of the fauna. The people were so of the group was Andrew phase III AVOREN trial amazingly welcoming”! Etherington. At age 75, Andrew • Prostate cancer death is unlikely in high-risk patients following Joining Roger were fellow has supported the TUF by quality permanent interstitial brachytherapy urologists John Fitzpatrick, participating in every challenge • Patient-specific risk of a missed cancer following investigation editor-in-chief of BJUI; Krishna Roger has organised. “Andrew for haematuria based on a four year follow up Patil from Surrey, UK; Roger Plail is a bit of a legend”, Roger • The prevalence of chronic constipation and fecal incontinence and Peter Rimington, both from explains, “having participated in among men and women with symptoms of overactive bladder East Sussex, UK; and Joseph 25 marathons as well as climbing t UROSCAN

t Mt. Kilimanjaro. ... He is an capital city of Antananarivo, toward the coast. “There were an flood-damaged tarmac and huge inspiration to all of us”. known locally as Tana. By the awful lot of long, uphill stretches undulating bumps”. next afternoon, they were hitting of road”, recalls John. “It was RIDE WAS NO PICNIC the road on their way to the extremely hot. One day we cycled THE CALL OF THE LEMUR As the fourth largest island in royal city of Ambohimanga in the rain. The elements were Other highlights of the trip the world, Madagascar is slightly Rova, with its palace and burial not on our side, making our ride included an overnight stay at larger than France. The vast grounds. A UNESCO world quite difficult”. Joe Kirby, Roger’s Lake Mantasoa in Tana, a visit majority of plants and animals heritage site, it remains a son, agrees, noting that “we to the Andasibe Nature Reserve, found there in its microclimates spiritual pilgrimage centre and cycled in torrential rain in the dinner on Lake Rasoa and a are endemic to the country. home to Tana history. rain forest. The visibility was very guided nature walk through After flying from London to Along the way, the participants poor, and it was very humid”. the zoological park in Ivoloina. Madagascar via Paris, the cyclists had to deal with some difficult Having studied international Krishna Patil often engaged the began their adventure in the riding as they toiled their way economics as part of his group with evening talks on Masters degree, Joe was quite Hinduism and meditation classes. Clinical Trial surprised at the quality of roads One evening in a remote village, in Madagascar. “Road quality is another rider, Georgina Stewart, a good indication of the level managed to put together an Title: of government corruption”, he impromptu party for Christian rd AA4500 IN THE TREATMENT OF PEYRONIE’S DISEASE explains. “I cycle a lot in France. Cooke’s 23 birthday. “It was held Even compared to some of at this small wooden building PROTOCOL ID: the roads there, the main road the people had managed to connecting the coast to the construct in the deepest part NCT 01221623 middle of the country was pretty of Madagascar”, says Joe with SUMMARY: good with very few potholes”. admiration. “The locals gave us Not all of the minor roads were music and dancing that night”. This phase 3, double-blind, randomized, placebo-controlled smooth, however. “On the last However, Joe, Christian and the study is evaluating the safety and efficacy of AA4500 for day, we journeyed by bus for two other younger riders couldn’t the treatment of Peyronie’s disease. Participants will be hours on a stretch of road that understand why the streets were stratified into groups depending on their degree of pe- nile curvature and then randomized into treatment or a had taken us only three hours to so deserted. “We didn’t realise placebo group (2:1 ratio). Following each treatment cycle, navigate by bike the day before”, they had a set curfew of 10 the investigator (or designee) will stretch the plaque to recalls Roger Plail. “Such was pm—a leftover from the civil war model it. Once curvature is lowered to less than 15º after the state of the highway with in the country just a year ago.“ one to three treatment cycles, no more treatment will be given. There will be a maximum of four treatment cycles per subject. Participants will continued to be monitored Important papers for safety and efficacy at various time intervals up to one you may have missed JOURNAL year. The primary outcome measures will be the percent improvement from baseline in penile curvature and the WATCH change from baseline in the Peyronie’s disease bother do- • O’Connor OJ, Fitzgerald E main, both at 52 weeks. Once they complete this protocol, and Maher MM. Imaging of subjects receiving placebo may opt to receive open-label hematuria. AJR: Amn J Roentgenol AA4500 as part of another study. 2010; 195: W263-W267 • Mendenhall WM, Nichols RC, Henderson R ELIGIBILITY: and Mendenhall NP. Is radical prostatectomy Subjects will be men age 18 years and older who are in the “gold standard” for localized prostate a stable relationship with a female partner/spouse for at cancer? Am J Clin Oncol 2010; 33: 511-515 least three months before screening. They must be willing • Westerlund A, Steineck G, Bälter K, et al. to have vaginal intercourse with the partner/spouse. Pey- Dietary supplement use patterns in men with ronie’s disease should be present for at least 12 months and be stable at the time of study entry. The penile cur- prostate cancer: the Cancer Prostate Sweden vature must be at last 30º in the dorsal, lateral or dorsal/ Study. Ann Oncol 2010; October 6. [Epub ahead lateral plane at screening. of print] • Cunningham GR and Toma SM. Why is LOCATIONS AND CONTACTS: androgen replacement in males controversial? There are 34 study locations in the US and Australia. For US J Clin Endocrinol Metab 2010; September 29. information, contact Karen Raudibaugh, Auxilium Phar- [Epub ahead of print] maceuticals, (484) 321-5900, ext. 2123, kraudibaugh@ • Soccorso G, Ninan GK, Rajimwale A et al. auxilium.com. For Australian information, contact Ni- Acute scrotum: is scrotal exploration the best gel Jones, Auxilium Pharmaceuticals, (44) 1443-421707, [email protected]. management? Eur J Pediatr Surg 2010; 20: 312-315 UROSCAN

going to stop for you”. Roger Plail also found the traffic scary at times. “Vehicles would come towards us two or three abreast. The drivers were bemused that Lycra-clad bike warriors would even dare contest the highway with them”. According to him, the riders often shared the road with trucks and ox-drawn makeshift pallet carts with noisy metal wheels. “We’d all be hurtling down hairpin turns overtaking them”. Another lasting memory was Riders were greeted by lemurs, Want to buy some beads? Roger Kirby gets the Mardi Gras the group’s visit to a remote whose eerie calls left a treatment from children at a Madagascar village. hospital, “which was incredibly powerful impression. poor”, remembers John. “The place was full of patients However, the greatest remain with all of us for quite as possible with no breaks—just with malaria and other tropical impression was made by the some time”, he says. “They have coasting”, remembers Roger. At diseases being treated with black and white Indri lemurs, a high-pitched shrill that echoes other times, riders had to share virtually no facilities at all”, Roger found only in the Madagascan and reverberates all around. It is the main, two-lane road leading recounts. “We raised over a rainforest and the largest of the one of the most striking noises to the coast with tractor-trailers thousand pounds to help them species. “You can walk through that I have ever heard”. carrying petrol and oil from get things going”. Among the the forests, see them in the trees the refineries. “Several times, items the money will be used for and hear them calling to each DODGING TRUCKS we were forced into the ditch are mosquito nets, cots, blankets, other”, Roger Kirby says. Of course, not all of the nearly by these lorries”, he points out. clothes, a sterilizer, microscope They definitely made a lasting 400 km of roads and off-road “If one lorry overtakes another, and a refrigerator. impression on John. “Hearing trails travelled were uphill. “There there isn’t much space to cycle their cry at the top of the were some great downhill runs through. You’d better get out MAKE WAY FOR THE ANDES rainforest is something that will where we were cycling as fast of the way quickly—they’re not All of the logistics for the TUF cycling trips, including lodging, meals, rest stops and DRUG AND TECHNOLOGY NEWS transportation of luggage and gear are handled by Classic Tours, UK RESIDENTS SURVEYED ABOUT BLADDER CANCER which organizes planning charity A national survey of residents living throughout the United Kingdom (UK) has revealed significant challenges. In February 2012, insights into the general public’s perception of bladder cancer and its causes and symptoms. their help will be enlisted again, Sponsored by Action on Bladder Cancer (ABC), the survey consisted of face-to-face interviews because Roger expects to lead with 2055 adults, age 16 years and older. Residents of Scotland, Wales and the rest of the UK were a group of cyclists to Argentina included in the survey. and Chile on a 470 km journey One finding was that more than half of those surveyed did not know the most common cause across the Andes. As before, all of bladder cancer. Too much alcohol use was cited by 18% of respondents. Just 5%, however, of the proceeds will go to TUF identified smoking as the main cause. Only 1% correctly said work-related chemicals were the (www.theurologyfoundation. second most common major risk factor. org) to benefit its research The majority of those surveyed did not know anyone who had bladder cancer. Only 14% admitted sponsorships, educational to knowing someone with the condition. Regionally, those most likely to know someone lived in programs and scholarships. For Yorkshire, Humberside and East Midlands, all considered industrialised areas in the UK. more information and to register, A quarter of respondents did not know the signs and symptoms of bladder cancer. Half of the visit Action for Charity at www. survey participants said that hematuria was the most common sign. Residents of Wales had the actionforcharity.co.uk. To get least understanding about symptoms among all regions surveyed. The vast majority of those inspired, you can view a video of interviewed (91%) would contact GP surgery if they were concerned about having bladder cancer. this year’s Madagascar trip and Interestingly, 12% felt the Internet would be a good option for additional information. hear comments from many of Release of the survey marks the establishment of ABC as a new charity in the UK. It aims to raise the riders on YouTube at http:// awareness of bladder cancer among the general public and provide support for those dealing www.youtube.com/watch ?v= with the condition. More information on ABC can be found by visiting their website at www. nPZk7V4XroE or by searching actionbladdercancer.org. for “Cycle Madagascar 2010”. UROSCAN In this issue... Urological Oncology

SEQUENTIAL THERAPY WITH TYROSINE DEATH FROM PROSTATE CANCER IS UNLIKELY AFTER BRACHYTHERAPY IN KINASE INHIBITORS IMPROVES SURVIVAL HIGH-RISK PATIENTS P226 IN RENAL CANCER PATIENTS P214 Patients are considered to have high-risk prostate cancer if they have a Gleason score of A variety of new therapies are designed to inhibit >8, a PSA of >20, or have a clinical stage of >T2c. These individuals are at the greatest risk vascular endothelial growth factor (VEGF) and for biochemical failure and death from their disease. More high-risk patients are now subsequent tumour angiogenesis in patients able to benefit from treatment with brachytherapy because of refinements in with clear-cell renal cell carcinoma. Ideally, the dose escalation and planning. In their case series, Merrick et al report on cause-specific goal of treatment is to inhibit VEGF throughout a survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in variety of therapies that target other pathways. high-risk patients receiving brachytherapy. They find that death from prostate cancer is Bracarda et al evaluate this approach using unlikely in these individuals. Instead, they are more likely to die from other causes, such as retrospective exploratory data from the Avastin heart diseases. for Renal Cell Cancer (AVOREN) trial. They find During a 10-year period, 284 high-risk prostate cancer patients underwent brachytherapy. that sequential bevacizumab plus interferon The majority of them (90.5%) also received external beam radiation therapy. In addition, therapy followed by tyrosine kinase 63.0% were prescribed short- or extended-course androgen deprivation therapy. Such inhibitors (TKIs) increases survival compared therapy was started three months before brachytherapy. After the procedure, patients were to standard first-line treatment alone. followed at three- to six-month intervals. In this study, 649 patients with untreated After 12 years, the CSS was 94.2%, while the bPFS was 89.0%. Overall survival was the metastatic renal cell carcinoma were randomized lowest at 69.7%. The best predictors of bPFS were the percent of positive biopsies and the to one of two arms. In the first arm, patients use of androgen deprivation therapy. Although there were no predictors found for CSS, received interferon with bevacizumab (10 mg/ there was a significant correlation between OS and the following factors: patient age, kg every two weeks). The second arm received percent of positive biopsies and diabetes. Overall, 14% of patients died from a variety of interferon and a placebo. Interferon was heart diseases. Death from heart diseases was more than twice as likely as death administered at 9 MIU three times a week for up from prostate cancer. Only 6% of patients died from prostate cancer, making aggressive to one year. Treatment in both arms continued lifestyle changes important for these patients to decrease their chance of dying from other until disease progression, unacceptable toxicity conditions, such as heart disease and diabetes. or withdrawal of consent. After progression, the use of any post-protocol anti-cancer therapy was Laparoscopic and Robotic Surgery permitted, including TKIs. All trial participants had confirmed metastatic renal cell carcinoma with ACHIEVING THE “TRIFECTA” AFTER LAPAROSCOPIC RADICAL >50% clear-cell histology and had underwent PROSTATECTOMY P274 either a total or partial nephrectomy. Urologists have taken a term from horse racing, the ‘trifecta’, to refer to a triple treatment A total of 327 patients received bevacizumab outcome in patients with prostate cancer undergoing surgery. The goal is to have plus interferon. Of these, 180 (55%) went on patients be continent, potent and cancer-free after two years. Ploussard et al to receive post-protocol therapy. Another 322 evaluate their own trifecta rate in patients undergoing extraperitoneal laparoscopic radical patients were randomized into the interferon plus prostatectomy (ELRP). They find that it is possible to achieve these three outcomes in more placebo arm; 202 (63%) of these later received than half of patients. additional treatment. In both groups receiving Their study consists of 911 patients, all of whom underwent ELRP by one of three surgeons post-protocol therapy, the most common between 2000 and 2007. They were followed for two years with regularly scheduled visits. treatment was TKIs. Patients from the original None of the 911 individuals were impotent or incontinent prior to surgery. A total of 563 treatment arm who subsequently received patients underwent bilateral and 177 underwent unilateral nerve-sparing surgery. The TKIs had a median overall survival of 38.6 patient’s average age was 62.1 years and the average prostate-specific antigen (PSA) level months. This compares with 33.6 months for was 9.9 ng/mL. There was non-organ-confined disease in 40.1% of patients. patients from the interferon plus placebo arm. An At one year, the trifecta outcome was achieved in 29.7% of patients. By the end of two additional retrospective analysis allowed for the years, this rate had increased to 54.5%. Having bilateral nerve-sparing surgery in- censoring of patients who received TKIs. In this creased this two-year trifecta rate even further to 63.5%. Men younger than age case, the median overall survival rate was 25.0 60 years at the time of surgery experienced a trifecta rate of 73.5%. In more than half of all months for patients from the treatment arm and patients not achieving the trifecta outcome at two years (55.6%), impotence was the prob- 20.7 months from the interferon plus placebo lem. Factors associated with trifecta outcomes were younger age, PSA levels of <10 ng/mL, arm. At present, the use of first-line bevacizumab bilateral nerve-sparing surgery, and organ-confined disease. Regardless of erectile function, plus interferon followed by TKIs should be there was good cancer control and regaining of continence in 84.8% of all patients. considered when planning treatment strategies for these patients.