Treatment of High-grade Non-muscle-invasive Bladder Carcinoma by Standard Number and Dose of BCG Instillations Versus Reduced Number and Standard Dose of BCG Instillations: Results of the European Association of Urology Research Foundation Randomised Phase III Clinical Trial "NIMBUS"
Language English Country Switzerland Media print-electronic
Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
32446864
DOI
10.1016/j.eururo.2020.04.066
PII: S0302-2838(20)30334-1
Knihovny.cz E-resources
- Keywords
- Bacillus Calmette-Guérin, Instillation therapy, Non–muscle-invasive bladder cancer, Reduced frequency,
- MeSH
- Adjuvants, Immunologic administration & dosage MeSH
- Administration, Intravesical MeSH
- BCG Vaccine administration & dosage MeSH
- Neoplasm Invasiveness MeSH
- Humans MeSH
- Urinary Bladder Neoplasms drug therapy pathology MeSH
- Prospective Studies MeSH
- Reference Standards MeSH
- Neoplasm Grading MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Names of Substances
- Adjuvants, Immunologic MeSH
- BCG Vaccine MeSH
BACKGROUND: Intravesical instillation of bacillus Calmette-Guérin (BCG) is an accepted strategy to prevent recurrence of non-muscle-invasive bladder cancer (NMIBC) but associated with significant toxicity. OBJECTIVE: NIMBUS assessed whether a reduced number of standard-dose BCG instillations are noninferior to the standard number and dose in patients with high-grade NMIBC. DESIGN, SETTING, AND PARTICIPANTS: A total of 345 patients from 51 sites were randomised between December 2013 and July 2019. We report results after a data review and safety analysis by the Independent Data Monitoring Committee based on the cut-off date of July 1, 2019. INTERVENTION: The standard BCG schedule was 6 wk of induction followed by 3 wk of maintenance at 3, 6, and 12 mo (15 instillations). The reduced frequency BCG schedule was induction at wks 1, 2, and 6 followed by 2 wk (wks 1 and 3) of maintenance at 3, 6, and 12 mo (nine instillations). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was time to first recurrence. Secondary endpoints included progression to ≥ T2 and toxicity. RESULTS AND LIMITATIONS: In total, 170 patients were randomised to reduced frequency and 175 to standard BCG. Prognostic factors at initial resection were as follows: Ta/T1: 46/54%; primary/recurrent: 92/8%; single/multiple: 57/43%; and concomitant carcinoma in situ: 27%. After 12 mo of median follow-up, the intention-to-treat analysis showed a safety-relevant difference in recurrences between treatment arms: 46/170 (reduced frequency) versus 21/175 patients (standard). Additional safety analyses showed a hazard ratio of 0.40 with the upper part of the one-sided 97.5% confidence interval of 0.68, meeting a predefined stopping criterion for inferiority. CONCLUSIONS: The reduced frequency schedule was inferior to the standard schedule regarding the time to first recurrence. Further recruitment of patients was stopped immediately to avoid harm in the reduced frequency BCG arm. PATIENT SUMMARY: After surgical removal of the tumour, patients with high-grade non-muscle-invasive bladder cancer are treated with bacillus Calmette-Guérin to prevent recurrence and progression. This is associated with significant side effects. We report the results of a clinical trial showing a reduction in the number of instillations (from 15 to nine in total) being inferior to the standard protocol. From today's perspective, complete tumour resection and a standard number of instillations remain the standard of care.
Department of Urology Acıbadem University Istanbul Turkey
Department of Urology Hospital Edouard Herriot Lyon France
Department of Urology Hospital Motol Charles University Prague Czech Republic
Department of Urology Hospital Universitario La Paz Madrid Spain
Department of Urology Jena University Hospital Jena Germany
Department of Urology Radboud UMC Nijmegen The Netherlands
Department of Urology University Hospitals Leuven Leuven Belgium
EAU Research Foundation Arnhem The Netherlands
EAU Research Foundation Arnhem The Netherlands; Skåne University Hospital Lund University Sweden
References provided by Crossref.org
Recurrence mechanisms of non-muscle-invasive bladder cancer - a clinical perspective
