304291008-Oa

Comments Emerging trends in prostate cancer literature: medical progress or marketing hype? †‡ Jonathon Lo*, Nathan Papa*, Damien M. Bolton*, Declan Murphy and † Nathan Lawrentschuk* § † *Department of Surgery, Austin Health, University of Melbourne, The Peter MacCallum Cancer Centre, ‡ Epworth Prostate Centre, Epworth Healthcare Richmond, and §Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Vic., Australia

[2,4]. Robot-assisted prostatectomy and proton beam therapy Introduction are two recent examples of overwhelming support in the Since the introduction of PSA testing, treatment options for literature and widespread adoption, despite a lack of quality clinically localised prostate cancer (PCa) have proliferated. evidence demonstrating superiority. A major contributing Prostate surgery, hormonal therapy and radiation therapy have factor to this phenomenon is company-sponsored research, rapidly grown in technique and delivery. Deferred intervention where there is an overriding purpose to maximise in the form of active surveillance or watchful waiting has been publications that reflect positively on a product, minimise widely adopted, while focal therapies using various energy publications of negative trials and to selectively emphasise techniques are gaining data as potential alternatives to radical certain parts of results [5]. treatment. The medical literature dedicated to PCa treatment A subanalysis of articles pertaining to cryosurgical ablation, a has exploded over this period, although an absence of high- more recent therapy gaining recognition for the treatment of quality evidence supporting one method over another is clinically localised PCa, was performed. In 2012, 20 apparent [1,2]. Consequently, healthcare workers and patients publications (out of 24) had a conflict of interest statement, have been inundated with PCa literature, but with little of which 12 (60%) acknowledged industry contributions. guidance on comparative effectiveness and harms of treatment. Company-sponsored research, an issue relevant for the This sheer volume of research raises concerns over its true broader medical literature and not just PCa, tends to be well value in improving the treatment and prevention of disease. Is cited and plays an influential role in the drug approval such literature actually beneficial to medical progress, or does it process, clinical practice guidelines and the prescribing amount to hyperbole and medical hype? practices of practitioners [5]. Misrepresentation and In the present article, we have examined trends in the PCa inaccuracies also filter through to media reports, which can literature by searching for treatment terms within a single greatly influence public opinion and patients’ beliefs about database (MEDLINE), from January 1992 to December 2012. which treatments to pursue. Search terms were applied as medical subject headings Another observed trend has been the inconsistent use of (MeSH) and free-text protocols (with truncation) in different terminology. Deferred intervention, for example, can be combinations pertaining to PCa. A number of concerning through either watchful waiting (also termed deferred trends have been identified from these literary findings. The treatment or symptom-guided treatment in the literature), first is the accelerated growth in PCa literature pertaining to with conservative management until the development of external beam radiotherapy (Fig. 1A), prostatectomy (Fig. 1B), symptoms, or active surveillance (also termed active deferred intervention (Fig. 1C) and focal therapy (Fig. 1D). monitoring) of the disease with intention to treat at Similarly, the number of urological journals returning searches thresholds that define progression, usually with PSA levels. for radical prostatectomy (from Fig. 1B) has substantially These terms are used interchangeably, in spite of distinct risen from 14 in 1992 to 68 in 2012. This trend of expanding patient characteristics. Evidently, once the use of incorrect journal listings coincides with an overall diversification in terms becomes common, their appearance throughout the subject matter, and hastened publication, all of which may literature is difficult to contain. compromise article size and depth of analysis [3]. Rectifying these trends requires contributions from researchers, A second development has been the marketing and review boards, editors and database administrators alike. implementation of new technologies long before the necessary Murphy [3] advocate that editors and review boards scrutinize determination of their effectiveness and adverse effects profile

Fig. 1 (A) Number of articles per year returning searches for external-beam radiotherapy of prostate cancer (PCa). IMRT, intensity-modulated radiotherapy; 3D-CRT, three-dimensional conformal radiotherapy; NOS, not otherwise speciﬁed. (B) Results by year for prostatectomy search terms robot-assisted (and related terms), laparoscopic and radical. (C) Results by year for deferred intervention terms of active surveillance and watchful waiting pertaining to PCa. (D) Results by year for searches of focal therapy. HIFU, high-intensity focused ultrasonography; VTP, vascular-targeted photodynamic therapy.

AB1400 200 Radical 1200 160 Image- 1000 guided Radical 120 IMRT 800 600 Robot 80 3D-CRT assisted

Number of results 400 Number of results Laparoscopic 40 External beam, NOS 200

0 0 1992 1996 2000 2004 2008 2012 2002 2004 2006 20082010 2012 Year Year

C D 80 200

60 150 Radiosurgery

Active Cryosurgical 100 surveillance 40 ablation VTP Watchful Number of results 50 Number of results waiting 20 HIFU

0 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 1992 1996 2000 2004 2008 2012 Year Year the basis of any proposed work, the questions being addressed the first stage of what should be considered a formal research in a study and their importance. This would probably project [2]. The latter approach should be used for necessitate tightening of the peer review process, a longer radiotherapy research investigating beyond a different dose, follow-up of clinical studies, and allowing more pages per fractionation schedule or target volume of previous article despite the risk of not being first to publish. For techniques [6]. Focal therapy, with perhaps the exception of prospective authors, this scenario would entail a greater focus cryosurgical ablation, should remain as an investigational on research methodology with early involvement of those therapy subject to rigorous evaluation before its widespread trained in quantitative methods. Authors should be transparent application as PCa treatment [4]. Randomised controlled in their disclosure of commercial sponsorship agreements to trials are the ‘gold standard’ for assessing clinical ensure journal editors can appreciate the circumstances by effectiveness. These may not be feasible in the early stages of which manuscripts are submitted. Sismondo and Doucet [5] technical innovation, such as in determining safety or promote the rejection of all sponsored trials because of the feasibility of the technology, in which case prospective unjustified risk to trial participants and the general public; comparative cohort studies with the establishment of national however, this stance fails to appreciate the considerable or international treatment registers should be undertaken [6]. funding required for conducting many of these trials. Using standardised terms through the efforts of researchers For progress in PCa treatment to continue, research that and database administrators will improve international builds on the work of previous projects must be conducted collaboration and communication between healthcare with the overall goal of advancing scientific knowledge. professionals, researchers and patients. In addition, database Researching novel technology, for instance, can take the searches should be regularly updated to keep pace with approach of incremental advances of an existing technique or current trends in PCa treatment. For example, MEDLINE

© 2015 The Authors BJU International © 2015 BJU International 15 Comments which uses indexing rules (like MeSH) to maximise searches References for retrievable and relevant articles, currently has no MeSH 1 Robertson C, Close A, Fraser C et al. Relative effectiveness of robot- indexing for active surveillance. Since 2008, active surveillance assisted and standard laparoscopic prostatectomy as alternatives to open has surpassed watchful waiting (which has its own MeSH) as radical prostatectomy for treatment of localised prostate cancer: a the more commonly cited literature term (Fig. 1C). Similarly, systematic review and mixed treatment comparison meta-analysis. BJU Int 2013; 112: 798–812 robot-assisted prostatectomy has no MeSH indexing, yet is a fi 2 Efstathiou JA, Gray PJ, Zietman AL. Proton beam therapy and localised separate procedure encompassing its own morbidity pro le to prostate cancer: current status and controversies. Br J Cancer 2013; 108: its open counterpart, which has MeSH indexing. In 1225–30 comparison, laparoscopic cholecystectomy has had individual 3 Murphy WM. Media hype in the medical literature: what’s a doctor to MeSH indexing since 1993. do? J Urol 2000; 163: 916–8 4 Murphy DG, Walton TJ, Connolly S, Costello AJ. Focal therapy for The first step in resisting these trends is awareness of the localised prostate cancer: are we asking the correct research questions? issues. Researchers and editors need to be ever mindful of BJU Int 2012; 109: 1–3 integrity and relevance in PCa research. Overall, greater 5 Sismondo S, Doucet M. Publication ethics and the ghost management of attention is required of the language we use in PCa literature medical publication. Bioethics 2010; 24: 273–83 and databases such as MEDLINE need to be proactive in this 6 van Loon J, Grutters J, Macbeth F. Evaluation of novel radiotherapy technologies: what evidence is needed to assess their clinical and cost regard. A lack of standardisation has a number of important effectiveness, and how should we get it? Lancet Oncol 2012; 13: e169–77 implications in PCa care, in particular, limiting access to best available evidence and the accuracy of systematic reviews, Correspondence: Nathan Lawrentschuk, Department of hindering communication and international collaboration. Surgery, University of Melbourne, Austin Hospital Suite 5, 210 Burgundy Street, Heidelberg, Vic. 3084, Australia. Conflict of Interest e-mail: [email protected] Nathan Lawrentschuk, Damien M. Bolton and Declan Murphy perform robot-assisted prostatectomies. Declan Abbreviations: PCa, prostate cancer; MeSH, medical subject Murphy has received honoraria for travel support, advisory headings. board and proctoring of robotic surgery from Intuitive Surgical and Device Technologies Australia.

A lot of questions (and a few answers ...)in retroperitoneal ﬁbrosis † ‡ Archie Fernando, James Pattison , Catherine Horsﬁeld , Matthew Bultitude, David D’Cruz§ and Tim O’Brien † ‡ Departments of Urology, Nephrology, Histopathology, and §Immunology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

pertinent clinical questions remain unanswered. Is a biopsy Introduction always required? What is an appropriate initial serological In 1939, Churchill memorably described Russia as ‘a riddle screen? Best imaging? Is RPF a basket of distinct diseases wrapped in a mystery inside an enigma’ [1]. He could have with a common endpoint or is there a unifying pathology? been talking of retroperitoneal fibrosis (RPF). Now, 109 years Can the disease be cured or only suppressed? What is the after it was first described by Albarran [2], RPF remains an basis for the severe pain experienced by some? Do all patients enigma, challenging to diagnose and very challenging to treat. require steroids or is a more selective approach required? In The pathogenesis is uncertain, there is no accepted some is the episode of RPF time-limited, eventually ‘burning classification and there are no published guidelines. itself out’? In keeping with other fibro-inflammatory disorders, might the new biological immune suppressors, e.g. Urologists are central to the management of RPF because rituximab, offer a more targeted approach to disease obstructive renal failure is a common feature, but the best management? The description of IgG4-related disease in 2003 long-term solution for ureteric obstruction is fiercely debated. and its undoubted involvement in some cases of RPF has In essence: who should have ureterolysis? A host of other added further intrigue to the clinical mix [3].