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

Abstract

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

FIG 1.

Consort diagram for the BRAVO feasibility study. mBCG, maintenance Bacillus Calmette-Guerin; QOL, quality of life; RC, radical cystectomy.

FIG 2.

Generic health-related quality of life for patients in the BRAVO feasibility study as measured using the EuroQuol-5D (EQ5D) and EORTC QLQ-C30 questionnaires. The EORTC-QLQ-C30 scores and the EQ-5D-3L Health score today range from 0 to 100, with high scores indicating better self-reported health. The EQ-5D-3L Score is calculated using dimensions from the questionnaire and high scores indicating better self-reported health. The number of completed questionnaires is shown above each column (see the Data Supplement for more details). BCG, Bacillus Calmette-Guerin; RC, radical cystectomy.

FIG 3.

Bladder cancer-specific EORTC PROMs questionnaire outcomes. Scores range from 0 to 100. A high score for urinary symptoms, future worries, and abdominal bloating and flatulence represents a high level of symptomatology. A high score for sexual functioning represents a high level of functioning. For individual items (malaise, intravesical treatment issues and risk of contaminating partner, body image scale, and urostomy problems), a high score is interpreted as worse. Merged scores are generated from the matching scales from either questionnaire and presented together. The number of completed questionnaires is shown above each column (see the Data Supplement for more details). BCG, Bacillus Calmette-Guerin; RC, radical cystectomy.