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

• Published in: The Journal of urology Vol. 198; no. 3; pp. 503 - 510
• Main Authors: Boehm, Brock E, Cornell, John E, Wang, Hanzhang, Mukherjee, Neelam, Oppenheimer, Jacob S, Svatek, Robert S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017
• Subjects: Adjuvants, Immunologic - therapeutic use; BCG vaccine; BCG Vaccine - therapeutic use; Humans; immunotherapy; Mycobacterium bovis; urinary bladder neoplasms; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Urology; carcinoma in situ; FDA; bacillus Calmette-Guérin; NMIBC; Netherlands National Institute for Public Health and the Environment; BCG; RIVM; MeSH; PRISMA; SUCRA; Preferred Reporting Items for Systematic Reviews and Meta-Analyses; nonmuscle invasive bladder cancer; CIS; BCG vaccine; surface under the cumulative ranking curve; immunotherapy; urinary bladder neoplasms; Medical Subject Headings; United States Food and Drug Administration
• ISSN: 0022-5347; 1527-3792; 1527-3792
• DOI: 10.1016/j.juro.2017.01.086

Purpose We sought to determine the efficacy of genetically distinct bacillus Calmette-Guérin 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-Guérin strains against all possible comparators (different bacillus Calmette-Guérin strains, chemotherapy and nonbacillus Calmette-Guérin 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-Guérin. 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 127 (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-Guérin strain demonstrated significant superiority when compared to any other strain at preventing recurrence in our network meta-analysis. Conclusions Bacillus Calmette-Guérin 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-Guérin efficacy.