EUROPEAN UROLOGY 66 (2014) 263–264 available at www.sciencedirect.com journal homepage: www.europeanurology.com

Platinum Priority – Editorial Referring to the article published on pp. 253–262 of this issue So Much Cost, Such Little Progress

Richard T. Bryan a,b,*, Roger Kirby c,d, Tim O’Brien e,f, Hugh Mostafid g,h a School of Cancer Sciences, University of Birmingham, Birmingham, UK; b Royal Society of Medicine Section of Urology, London, UK; c The Prostate Centre, London, UK; d The Urology Foundation, London, UK; e Guy’s and St. Thomas’ NHS Foundation Trust, London, UK; f British Association of Urological Surgeons Section of Oncology, London, UK; g Royal Berkshire NHS Foundation Trust, Reading, UK; h Action on Bladder Cancer, London, UK

Urothelial bladder cancer (UBC) is burdensome for patients In this month’s issue of European Urology, Svatek et al. and expensive for health care providers [1]. Outcomes have provide a review of the costs and other considerations for changed little for three decades, despite significant these approaches and discuss key issues regarding the improvements in 5-yr survival rates for prostate and kidney wider economics of UBC care [6]. Their review represents a cancers during this period [1]. Patient pathways are useful overview for the practicing urologist. In particular, complex, prolonged, and practised in various permutations the authors demonstrate that there are large gaps in our at every stage: knowledge regarding the efficacy and cost-effectiveness of these approaches and a lack of sufficiently powered  The investigation of patients with suspected UBC requires randomized controlled trials (RCTs), with expensive tools multiple diagnostic procedures [2,3]; various combina- having crept into everyday practice without the necessary tions of tests are used [4]. thorough evaluations. The authors highlight that there is a  Transurethral resection of bladder tumor can be per- clear and urgent need for the development of new drugs for formed by a number of different techniques with a UBC, both non-MIBC (NMIBC) and MIBC. The prevalence of number of different energy sources, and using a variety of NMIBC and its protracted course compared with MIBC is optical image enhancement technologies [5]. such that the cumulative cost of care is thought to be even  Further treatment may be required in the form of more substantial than for MIBC [6], so the gains to be made intravesical therapy with various agents, with or without in preventing recurrence and progression of NMIBC could chemohyperthermia or electromotive drug administra- be the most significant. The individual physician has the tion [3]. greatest impact on the cost of care of NMIBC, yet variation in  Long-term surveillance is the mainstay of subsequent treatment intensity does not affect survival or the management [2,3]; various surveillance schedules are avoidance of subsequent major interventions [6]. practised [6]. Other authors have recently highlighted these and  Surveillance may or may not use urinary biomarkers, and other issues in UBC care [1]. However, to make practice- treatment of recurrence may be carried out in the office or changing recommendations, robust and detailed assess- the operating theater [6]. ments of specific elements of these complicated pathways  For curative intent, patients who present with or progress are required, using complex modeling and statistics and to muscle-invasive bladder cancer (MIBC) are treated measures of cost-effectiveness. Such analyses have previ- by radiotherapy [2,7], chemoradiotherapy [8], radical ously been undertaken in the United Kingdom in the form of cystectomy (open, laparoscopic, or robot-assisted), or Health Technology Assessments [4,9]. Reasonably, Svatek neoadjuvant chemotherapy followed by radical cystec- et al. do not venture into this complex territory, but such tomy [2,7]; adjuvant chemotherapy is used in some units. health services research is urgently needed alongside basic

DOI of original article: http://dx.doi.org/10.1016/j.eururo.2014.01.006. * Corresponding author. School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Tel. +44 121 414 7870; Fax: +44 121 414 2230. E-mail address: [email protected] (R.T. Bryan). http://dx.doi.org/10.1016/j.eururo.2014.02.031 0302-2838/# 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. 264 EUROPEAN UROLOGY 66 (2014) 263–264 and translational research and clinical trials [1]. Furthermore, nonurologic scientific community [1]. And where are the nonmedical costs associated with UBC care (that are MIBC’s innovative new drugs? It feels as though the borne by patients, their families, and their employers) and pharmaceutical industry has deserted UBC in search of the costs associated with untimely deaths due to UBC are lower-hanging fruit. These issues were specifically dis- simply staggering [6]. Perhaps the treatment of UBC has far cussed among leading UK urologists and oncologists at the more impact on health-related quality of life than we have Royal Society of Medicine Section of Urology Annual Winter previously realized? Meeting in January, and it was concluded that the Royal The authors could have been more prescriptive in their Society of Medicine, the British Association of Urological conclusions to send a clearer message. For example, they Surgeons, the Urology Foundation, and Action on Bladder present data that level 1 evidence and clinical guidelines are Cancer should endeavor to undertake a collaborative and being ignored [1,6], yet they fail to recommend that such concerted effort to advance the cause for UBC patients. We evidence and guidelines be more closely adhered to. Perhaps need to make much more progress, perhaps improving cost- we do not actually need more RCTs of bacillus Calmette- effectiveness along the way. Gue´rin (BCG) maintenance therapy, which are both expen- sive and protracted. Instead, would a better use of resources Conflicts of interest: Richard T. Bryan has contributed to an advisory be to gain a clearer understanding of BCG’s mechanism of board for Olympus Medical Systems with regard to narrow band imaging action and the immunologic milieu of the bladder tumor cystoscopy. Tim O’Brien is a speaker for GE Healthcare and Photocure. He has contributed to an advisory board for Ipsen Pharma. microenvironment, potentially leading to the development of new therapeutics for all UBC patients? NMIBC is also an ideal setting in which to assess the effectiveness of novel References low-toxicity therapeutics and/or chemopreventive agents [1] Kaplan AL, Litwin MS, Chamie K. The future of bladder cancer care in administered long-term—and several such RCTs (eg, BOXIT, the USA. Nat Rev Urol 2014;11:59–62. SELENIB) are in follow-up—yet such strategies are not [2] Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet discussed by the authors. As for urinary biomarkers, their 2009;374:239–49. real utility may not actually lie in their ability to detect new or [3] Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non- recurrent disease but in their ability to risk stratify patients muscle-invasive urothelial carcinoma of the bladder: update 2013. early in their pathway so that they are investigated and Eur Urol 2013;64:639–53. managed more appropriately and expeditiously [10].Thereis [4] Rodgers M, Nixon J, Hempel S, et al. Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and a lot that we could do now to redesign these pathways and economic evaluation. Health Technol Assess 2006;10:iii–v, xi–259. interventions [10], yet there is a reluctance to change and a [5] Wilby D, Thomas K, Ray E, Chappell B, O’Brien T. Bladder cancer: significant lack of research funding [1]. new TUR techniques. World J Urol 2009;27:309–12. And it is this lack of research funding that underlies our [6] Svatek RS, Hollenbeck BK, Holma¨ng S, et al. The economics of complex and varied pathways. We do not actually have the bladder cancer: costs and considerations of caring for this disease. robust evidence base to support a lot of what we do, and Eur Urol 2014;66:253–62. where the robust evidence and high-grade recommenda- [7] Witjes JA, Compe´rat E, Cowan NC, et al. EAU guidelines on muscle- tions exist, the uptake is poor (eg, single-shot intravesical invasive and metastatic bladder cancer: summary of the 2013 mitomycin C [3], neoadjuvant platinum-based combination guidelines. Eur Urol 2014;65:778–92. chemotherapy [7]) [6]. Consequently, a spectrum of [8] James ND, Hussain SA, Hall E, et al. Radiotherapy with or without alternatives is practiced by individual urologists and/or chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012;366:1477–88. individual units, possibly accentuated in the United States [9] Mowatt G, Zhu S, Kilonzo M, et al. Systematic review of the clinical by illogical reimbursement patterns [1]. The authors’ lack of effectiveness and cost-effectiveness of photodynamic diagnosis and decisive conclusions is therefore understandable. urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the If we are to tackle UBC and improve outcomes, as we detection and follow-up of bladder cancer. Health Technol Assess have done for prostate and kidney cancer, we need to lobby 2010;14:1–331, iii–iv. for more funding for RCTs and translational science and [10] Bryan RT, Shimwell NJ, Wei W, et al. Urinary EpCAM in urothelial health services research, as well as address the poor bladder cancer patients: characterisation and evaluation of bio- awareness of UBC among the general public and the marker potential. Br J Cancer 2014;110:679–85.