Efficacy of Bacillus Calmette-Guerin Strains for the Treatment of Non-Muscle Invasive Bladder Cancer: A systematic review and network meta-analysis

Abstract

Purpose:

To determine the efficacy of genetically distinct Bacillus Calmette-Guérin (BCG) strains in preventing disease recurrence for patients with non-muscle invasive bladder cancer.

Materials and Methods:

We conducted a systematic review and network meta-analysis of trials evaluating BCG strains against all possible comparators (different BCG strains, chemotherapy, and non-BCG biologic therapies) and intravesical chemotherapy as the common comparator. MEDLINE served as the primary data source, with search from inception to April 2014 for clinical trials involving patients with NMIBC receiving BCG. Primary outcome measure was bladder cancer recurrence defined as recurrent bladder tumor of any grade or stage. Random-effects network meta-analysis provided estimates for outcomes and is presented as odds ratios (ORs).

Results:

Across all possible comparators (n=65 trials, 12,246 patients, 9 strains) there were 2,177 (38.6%) recurrences among 5,642 treated patients compared with 2,316 (42.6%) recurrences among 5,441 comparators. With chemotherapy as the common comparator (n=28 trials, 5,757 patients, 5 strains), Tokyo (0.39 OR 95% CI 0.16–0.93), Pasteur (0.49 OR 95% CI 0.28–0.86), and TICE (0.61 OR 95% CI 0.40–0.93) strains were significantly better than chemotherapy at preventing recurrence. No BCG strain demonstrated significant superiority when compared against any other strain at preventing recurrence in our network meta-analysis.

Conclusions:

BCG strains exhibit significant differences in efficacy when compared against chemotherapy. However, no definitive conclusions are reached regarding strain superiority and head-to-head trials are greatly needed to further understand the importance of strain selection in determining BCG efficacy.