Re: Radical Cystectomy Against Intravesical BCG for High-risk High-grade Nonmuscle Invasive Bladder Cancer: Results from the Randomized Controlled BRAVO-feasibility Study

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.

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BRAVO-Feasibility Study Underscores the Challenges of a Trial Comparing BCG Versus Radical Cystectomy in High-Risk Nonmuscle Invasive Bladder Cancer

Default Digital Object Group ◽

10.1200/adn.21.200567 ◽

2021 ◽

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Radical Cystectomy ◽

Feasibility Study ◽

Invasive Bladder Cancer ◽

Nonmuscle Invasive Bladder Cancer

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Re: 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

European Urology ◽

10.1016/j.eururo.2017.12.007 ◽

2018 ◽

Vol 73 (4) ◽

pp. 636 ◽

Cited By ~ 1

Author(s):

Karl H. Pang ◽

Aidan P. Noon

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Radical Cystectomy ◽

Feasibility Study ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Bcg Immunotherapy ◽

Intravesical Bcg ◽

Muscle Invasive ◽

Randomised Controlled

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945 Is intravesical BCG alone still the only truly effective intravesical therapy for high risk nonmuscle invasive bladder cancer?

European Urology Supplements ◽

10.1016/s1569-9056(15)60933-2 ◽

2015 ◽

Vol 14 (2) ◽

pp. e945 ◽

Cited By ~ 2

Author(s):

S.M. Di Stasi ◽

C. Riedl ◽

C. Verri ◽

F. Celestino ◽

F. De Carlo ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Invasive Bladder Cancer ◽

Intravesical Therapy ◽

Intravesical Bcg ◽

Nonmuscle Invasive Bladder Cancer

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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

BMJ Open ◽

10.1136/bmjopen-2017-017913 ◽

2017 ◽

Vol 7 (8) ◽

pp. e017913 ◽

Cited By ~ 13

Author(s):

Jamie B Oughton ◽

Heather Poad ◽

Maureen Twiddy ◽

Michelle Collinson ◽

Victoria Hiley ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Radical Cystectomy ◽

Feasibility Study ◽

Phase Iii ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Phase Iii Trial ◽

Muscle Invasive ◽

Randomised Controlled

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.

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Radical cystectomy compared to intravesical BCG immunotherapy for high-risk non-muscle invasive bladder cancer – is there a long-term survival difference? A Swedish nationwide analysis

Scandinavian Journal of Urology ◽

10.1080/21681805.2020.1851763 ◽

2020 ◽

pp. 1-7

Author(s):

Eugen Y-H Wang ◽

Ulf Larsson ◽

Truls Gårdmark ◽

Per-Uno Malmström

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Radical Cystectomy ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Term Survival ◽

Survival Difference ◽

Intravesical Bcg ◽

Muscle Invasive

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Definitive BCG immunotherapy versus radical cystectomy in intermediate or high-risk nonmuscle invasive bladder cancer patients

Medicine ◽

10.1097/md.0000000000016873 ◽

2019 ◽

Vol 98 (36) ◽

pp. e16873

Author(s):

Xiaoming Jian ◽

Mingkang Shen ◽

Guodong Liao

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Cancer Patients ◽

Radical Cystectomy ◽

Invasive Bladder Cancer ◽

Bcg Immunotherapy ◽

Nonmuscle Invasive Bladder Cancer

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A retrospective analysis of patients treated with intravesical BCG for high-risk nonmuscle invasive bladder cancer

Therapeutic Advances in Urology ◽

10.1177/1756287219833056 ◽

2019 ◽

Vol 11 ◽

pp. 175628721983305 ◽

Cited By ~ 1

Author(s):

Julie Mariam Joshua ◽

Meenu Vijayan ◽

Ginil Kumar Pooleri

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Disease Free Survival ◽

Invasive Bladder Cancer ◽

Progression Rate ◽

Therapeutic Effects ◽

Free Survival ◽

Bcg Therapy ◽

Intravesical Bcg ◽

Nonmuscle Invasive Bladder Cancer

Background: Adjuvant intravesical immunotherapy with Bacillus Calmette–Guerin (BCG) is considered as the first-line agent in patients with high-risk nonmuscle invasive bladder cancer (NMIBC) after surgery. There are no data in India where there is a high prevalence of tubercle bacillus and inherent immunity against Bacillus sp. The present study aims to evaluate the outcomes of intravesical BCG in the Indian population. Methods: A retrospective study of 101 patients who underwent intravesical BCG for high-risk NMIBC between January 2006 and December 2015 was carried out in a single centre. We compared the recurrence-free rate and progression rate of patients who received induction alone and induction with maintenance BCG therapy. The safety profile of intravesical BCG therapy was also assessed in the study. Results: After a median follow up of 2 years, the disease-free survival (DFS) rates of the induction group and maintenance group were 82% and 88% respectively ( p = 0.233). There was no difference in progression-free survival (PFS) rates at 2 years in those who receive maintenance BCG (95%) and those with induction BCG (94.7%; p = 0.721). A total of 69.36% of our patients had local adverse events. Conclusion: Our results suggest that maintenance therapy does not enhance the therapeutic effects of BCG in patients who respond favourably to 6 weeks of induction. Additional prospective studies are warranted in those countries where tuberculosis exposure is prevalent.

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