Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis

Francesco del Giudice, Vincenzo Asero, Eugenio Bologna, Carlo Maria Scornajenghi, Dalila Carino, Virginia Dolci, Pietro Viscuso, Stefano Salciccia, Alessandro Sciarra, David D’Andrea, Benjamin Pradere, Marco Moschini, Andrea Mari, Simone Albisinni, Wojciech Krajewski, Tomasz Szydełko, Bartosz Małkiewicz, Łukasz Nowak, Ekaterina Laukhtina, Andrea GallioliLaura S. Mertens, Gautier Marcq, Alessia Cimadamore, Luca Afferi, Francesco Soria, Keiichiro Mori, Karl Heinrich Tully, Renate Pichler, Matteo Ferro, Octavian Sabin Tataru, Riccardo Autorino, Simone Crivellaro, Felice Crocetto, Gian Maria Busetto, Satvir Basran, Michael L. Eisenberg, Benjamin Inbeh Chung, Ettore de Berardinis

Research output: Contribution to journalReview articleAcademicpeer-review

2 Citations (Scopus)


Background: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. Methods: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. Results: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16–0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. Conclusion: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.
Original languageEnglish
Article number1937
Issue number7
Publication statusPublished - 1 Apr 2023


  • BCG immunotherapy
  • BCG strain
  • bladder cancer
  • network meta-analysis
  • non-muscle invasive bladder cancer
  • recurrence rate

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