A systematic review and meta-analysis on the safety and efficacy of different strains of Mycobacterium bovis bacillus Calmette-Guérin for non-muscle invasive bladder cancer in Japan and US

Objective: To compare efficacy and safety of different strains of Mycobacterium bovis bacillus Calmette-Guérin (BCG) used in Japan and the US as intravesical therapeutics for non-muscle invasive bladder cancer. Materials and methods: Papers for review were selected from PubMed and Igakuchuozasshi databases, and meta-analysis was performed using the data obtained. Results: 352 papers from Japanese hospitals and 333 papers from US hospitals were reviewed. Strains used in Japan were Immunobladder®> (Tokyo 172) and ImmuCyst® (Connaught (JP)), while those used in the US were TICE® (TICE) and TheraCys® (Connaught (US)). CR (complete remission) rates for patients with CIS (carcinoma in situ) were 0.824 (n = 380, 95% CI 0.782–0.861), 0.868 (n = 38, 95% CI 0.719–0.956), 0.714 (n = 35, 95% CI 0.537–0.854) and 0.574 (n = 385, 95% CI 0.523–0.624) for Tokyo 172, Connaught (JP), TICE and Connaught (US), respectively. Non- recurrence survival (NRS) rates for non-CIS patients were 0.754 (n = 429, 95% CI 0.714–0.794), 0.790 (n = 83, 95% CI 0.702–0.878), 0.673 (n = 250, 95% CI 0.615–0.731) and 0.598 (n = 255, 95% CI 0.538–0.658) for Tokyo 172, Connaught (JP), TICE and Connaught (US), respectively. Conclusion: No significant differences were observed neither in efficacy nor in safety between two strains of BCG used Japan and the US. However, the rates of CR and NRS may be higher in Japan than the US, and the rates of severe adverse events may be higher in Japan than the US, although the data were not from controlled studies.