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.
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.
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.
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).
The primary endpoint was time to first recurrence. Secondary endpoints included progression to ≥ T2 and toxicity.
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.
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.
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.
European urology. 2020 May 20 [Epub]
Marc-Oliver Grimm, Antoine G van der Heijden, Marc Colombel, Tim Muilwijk, Luis Martínez-Piñeiro, Marko M Babjuk, Levent N Türkeri, Joan Palou, Anup Patel, Anders S Bjartell, Christien Caris, Raymond G Schipper, Wim P J Witjes, EAU Research Foundation NIMBUS Study Group
Department of Urology, Jena University Hospital, Jena, Germany. Electronic address: ., Department of Urology, Radboud UMC, Nijmegen, The Netherlands., Department of Urology, Hospital Edouard Herriot, Lyon, France., Department of Urology, University Hospitals Leuven, Leuven, Belgium., Department of Urology, Hospital Universitario La Paz, Madrid, Spain., Department of Urology, Hospital Motol, Charles University, Prague, Czech Republic., Department of Urology, Acıbadem University, Istanbul, Turkey., Urology Department, Fundació Puigvert, Barcelona, Spain., London, UK., EAU Research Foundation, Arnhem, The Netherlands; Skåne University Hospital, Lund University, Sweden., EAU Research Foundation, Arnhem, The Netherlands.