Radical cystectomy (bladder removal) against intravesical BCG immunotherapy for high-risk non-muscle invasive bladder cancer (BRAVO): a protocol for a randomised controlled feasibility study

Abstract

IntroductionHigh-risk non-muscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease that can be difficult to predict. While around 25% of cancers progress to invasion and metastases, the remaining majority of tumours remain within the bladder. It is uncertain whether patients with HRNMIBC are better treated with intravesical maintenance BCG (mBCG) immunotherapy or primary radical cystectomy (RC). A definitive randomised controlled trial (RCT) is needed to compare these two different treatments but may be difficult to recruit to and has not been attempted to date. Before undertaking such an RCT, it is important to understand whether such a comparison is possible and how best to achieve it.Methods and analysisBRAVO is a multi-centre, parallel-group, mixed-methods, individually randomised, controlled, feasibility study for patients with HRNMIBC. Participants will be randomised to receive either mBCG immunotherapy or RC. The primary objective is to assess the feasibility and acceptability of performing the definitive phase III trial via estimation of eligibility and recruitment rates, assessing uptake of allocated treatment and compliance with mBCG, determining quality-of-life questionnaire completion rates and exploring reasons expressed by patients for declining recruitment into the study. We aim to recruit 60 participants from six centres in the UK. Surgical trials with disparate treatment options find recruitment challenging from both the patient and clinician perspective. By building on the experiences of other similar trials through implementing a comprehensive training package aimed at clinicians to address these challenges (qualitative substudy), we hope that we can demonstrate that a phase III trial is feasible.Ethics and disseminationThe study has ethical approval (16/YH/0268). Findings will be made available to patients, clinicians, the funders and the National Health Service through traditional publishing and social media.Trial registration numberISRCTN12509361; Pre results.

Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

“…To further evaluate the efficacy of RC in high‐risk BCG‐naïve patients, a randomized feasibility trial (BRAVO) has just finished recruiting patients to undergo either RC or BCG maintenance . Their results are highly anticipated to help determine the safety of a subsequent phase III trial.…”

Immunological Approaches Towards Cancer and Inflammation: A Cross Talk

“…In patients with RB status, the response was higher than 80%, whereas in those receiving six weekly doses, the response was 70%. However, phase 2/3 trials are underway for its complete evaluation ( 141 , 142 , 144 ). Correspondingly sipuleucel-T is the first FDA-licensed cellular immune therapy vaccine against non-viral cancer ( 145 ).…”

Advances in risk stratification of bladder cancer to guide personalized medicine

“…micropapillary, plasmacytoid, nested), or concomitant CIS have all been associated with increased risk of progression and are best managed with surgery 108 – 113 . A group from the United Kingdom has designed a prospective, randomized controlled trial, with end of accrual set for March 2018, comparing immediate cystectomy against BCG induction with maintenance therapy for a “very high-risk” population of NMIBC patients 114 . Notably excluded from their cohort are any patients with variant histology.…”