TY - JOUR
T1 - Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs)
T2 - Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis
AU - del Giudice, Francesco
AU - Asero, Vincenzo
AU - Bologna, Eugenio
AU - Scornajenghi, Carlo Maria
AU - Carino, Dalila
AU - Dolci, Virginia
AU - Viscuso, Pietro
AU - Salciccia, Stefano
AU - Sciarra, Alessandro
AU - D’Andrea, David
AU - Pradere, Benjamin
AU - Moschini, Marco
AU - Mari, Andrea
AU - Albisinni, Simone
AU - Krajewski, Wojciech
AU - Szydełko, Tomasz
AU - Małkiewicz, Bartosz
AU - Nowak, Łukasz
AU - Laukhtina, Ekaterina
AU - Gallioli, Andrea
AU - Mertens, Laura S.
AU - Marcq, Gautier
AU - Cimadamore, Alessia
AU - Afferi, Luca
AU - Soria, Francesco
AU - Mori, Keiichiro
AU - Tully, Karl Heinrich
AU - Pichler, Renate
AU - Ferro, Matteo
AU - Tataru, Octavian Sabin
AU - Autorino, Riccardo
AU - Crivellaro, Simone
AU - Crocetto, Felice
AU - Busetto, Gian Maria
AU - Basran, Satvir
AU - Eisenberg, Michael L.
AU - Chung, Benjamin Inbeh
AU - de Berardinis, Ettore
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - 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.
AB - 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.
KW - BCG immunotherapy
KW - BCG strain
KW - bladder cancer
KW - network meta-analysis
KW - non-muscle invasive bladder cancer
KW - recurrence rate
UR - http://www.scopus.com/inward/record.url?scp=85152886847&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers15071937
DO - https://doi.org/10.3390/cancers15071937
M3 - Review article
C2 - 37046598
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 7
M1 - 1937
ER -