Efficacy of bacillus Calmette-Guerin Strains for Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Network Meta-Analysis

Purpose: We sought to determine the efficacy of genetically distinct bacillus Calmette-Guerin strains in preventing disease recurrence in patients with nonmuscle invasive bladder cancer. Materials and Methods: We conducted a systematic review and network meta-analysis of trials evaluating bacillus Calmette-Guerin strains against all possible comparators (different bacillus Calmette-Guerin strains, chemotherapy and nonbacillus Calmette-Guerin biological therapies) with intravesical chemotherapy as the common comparator. MEDLINE(http://www.ncbi.nlm.nih.gov/pubmed) served as the primary data source, with the search from inception to October 2016 for clinical trials involving patients with nonmuscle invasive bladder cancer receiving bacillus Calmette-Guerin. Primary outcome measure was bladder cancer recurrence, defined as recurrent bladder tumor of any grade or stage. Random effect network meta-analysis provided estimates for outcomes and is presented as odds ratios. Results: Across all possible comparators (65 trials, 12,246 patients, 9 strains) there were 2,177 recurrences in 5,642 treated patients (38.6%) and 2,316 recurrences in 5,441 comparators (42.6%). With chemotherapy as the common comparator (28 trials, 5,757 patients, 5 strains) Tokyo-172 (OR 0.39, 95% CI 0.16-0.93), Pasteur (OR 0.49, 95% CI 0.28-0.86) and TICE(OR 0.61, 95% CI 0.40-0.93) strains were significantly better than chemotherapy at preventing recurrence. No bacillus Calmette-Guerin strain demonstrated significant superiority when compared to any other strain at preventing recurrence in the network meta-analysis. Conclusions: Bacillus Calmette-Guerin strains exhibited significant differences in efficacy compared to chemotherapy. However, no definitive conclusions could be reached regarding strain superiority, and head-to-head trials are greatly needed to further understand the importance of strain selection in determining bacillus Calmette-Guerin efficacy.