Neoadjuvant treatment for muscle-invasive bladder cancer: The past, the present, and the future

Approximately half of patients who undergo radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) will succumb to metastatic disease. We summarize the evidence for neoadjuvant radiation (NAR), chemo (NAC), and immunotherapy (checkpoint inhibition) prior to RC for MIBC.

Data were obtained by a search of PubMed, ClinicalTrials.gov, and Cochrane databases for English language articles published from 1925 up to 2017.

NAC usage has increased over the last decade, while NAR is rarely administered. Although NAR results in downstaging, its impact on survival is inconclusive. Based on level I evidence, cisplatin-based NAC (CB-NAC) is considered standard of care in cT2-4aN0M0 MIBC. NAC results in a 6% absolute 10-year overall survival (OS) benefit. In-depth analyses of key randomized controlled trials showed that failure to correct for uniform staging, surgical variation, and patient selection compromises the ability to identify factors predictive of response to NAC. The benefit appears to be restricted to patients downstaged to ypT1N0 or less. In these patients, 5-year OS is 80% to 90%. Regarding a number needed to treat of 17, most patients with cT2-4aN0M0 MIBC will be exposed to toxicity without benefit. Possible approaches to reduce overtreatment are suggested in this article and include patient selection, the chosen NAC regimen, and emerging molecular data to predict responsiveness to NAC. Neoadjuvant immunotherapy with checkpoint inhibitors is a promising future perspective currently under investigation.

Past studies on NAR show inconclusive results and NAR is rarely administered. Instead, CB-NAC is advised in eligible patients with cT2-4aN0M0 MIBC prior to RC. In the near future, predictive biomarkers will be the key to tailor the use of CB-NAC and reduce harm to nonresponders.

Urologic oncology. 2017 Nov 08 [Epub ahead of print]

Tom J N Hermans, Charlotte S Voskuilen, Michiel S van der Heijden, Bernd J Schmitz-Dräger, Wassim Kassouf, Roland Seiler, Ashish M Kamat, Petros Grivas, Anne E Kiltie, Peter C Black, Bas W G van Rhijn

Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Department of Medical Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Department of Urology, Friedrich-Alexander University, Erlangen, Germany; Department of Urology, Schön-Klinik, Nürnberg/Fürth, Germany., Department of Surgery, Division of Urology, McGill University Health Center, Montreal, Canada., Department of Urology, Inselspital, University of Bern, Bern, Switzerland., Department of Urology, The University of Texas, MD Anderson Cancer Center, Houston, TX., Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH., Department of Radiation Oncology, CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom., Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada., Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address: .

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