Radical Cystectomy Against Intravesical BCG for High-Risk High-Grade Nonmuscle Invasive Bladder Cancer: Results From the Randomized Controlled BRAVO-Feasibility Study.

High-grade nonmuscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease. Treatments include intravesical maintenance Bacillus Calmette-Guerin (mBCG) and radical cystectomy (RC). We wanted to understand whether a randomized trial comparing these options was possible.

We conducted a two-arm, prospective multicenter randomized study to determine the feasibility in Bacillus Calmette-Guerin-naive patients. Participants had new high-risk HRNMIBC suitable for both treatments. Random assignment was stratified by age, sex, center, stage, presence of carcinoma in situ, and prior low-risk bladder cancer. Qualitative work investigated how to maintain equipoise. The primary outcome was the number of patients screened, eligible, recruited, and randomly assigned.

We screened 407 patients, approached 185, and obtained consent from 51 (27.6%) patients. Of these, one did not proceed and therefore 50 were randomly assigned (1:1). In the mBCG arm, 23/25 (92.0%) patients received mBCG, four had nonmuscle invasive bladder cancer (NMIBC) after induction, three had NMIBC at 4 months, and four received RC. At closure, two patients had metastatic BC. In the RC arm, 20 (80.0%) participants received cystectomy, including five (25.0%) with no tumor, 13 (65.0%) with HRNMIBC, and two (10.0%) with muscle invasion in their specimen. At follow-up, all patients in the RC arm were free of disease. Adverse events were mostly mild and equally distributed (15/23 [65.2%] patients with mBCG and 13/20 [65.0%] patients with RC). The quality of life (QOL) of both arms was broadly similar at 12 months.

A randomized controlled trial comparing mBCG and RC will be challenging to recruit into. Around 10% of patients with high-risk HRNMIBC have a lethal disease and may be better treated by primary radical treatment. Conversely, many are suitable for bladder preservation and may maintain their prediagnosis QOL.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020 Dec 17 [Epub ahead of print]

James W F Catto, Kathryn Gordon, Michelle Collinson, Heather Poad, Maureen Twiddy, Mark Johnson, Sunjay Jain, Rohit Chahal, Matt Simms, Mohantha Dooldeniya, Richard Bell, Phillip Koenig, Samantha Conroy, Louise Goodwin, Aidan P Noon, Julie Croft, Julia M Brown, BRAVO study group

Academic Urology Unit, University of Sheffield, Sheffield, United Kingdom., Clinical Trials Research Unit, Leeds Institute for Clinical Trials Research, University of Leeds, Leeds, United Kingdom., Institute of Clinical and Applied Health Research, University of Hull, Hull, United Kingdom., Freeman Hospital, Newcastle, United Kingdom., St James's University Hospital, Leeds, United Kingdom., Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom., Hull and East Yorkshire NHS Trust, Hull, United Kingdom., Mid Yorkshire Hospitals NHS Trust, Wakefield, United Kingdom., Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom., Airedale NHS Foundation Trust, Keighley, United Kingdom., Department of Urology, Royal Hallamshire Hospital, Sheffield, United Kingdom.

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