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

Abstract

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.

Chest wall tumor following intravesical BCG instillation for non-muscle invasive bladder cancer

“…Connaught, Tice, and RIVM) are also resistant to cycloserine. Depending on the exact BCG strain, some patients benefit from additional, though less common, use of fluoroquinolones (like ofloxacin, ciprofloxacin, moxifloxacin, and levofloxacin) [26] . The use of corticosteroids within antimycobacterial treatment in patients with disseminated BCG infection highlights its presumptive underlying pathogenetic etiology of both hypersensitivity reaction and active infection.…”

Comparing Clinical Efficacy of Different Bacillus Calmette-Guérin Strains in Patients With T1 High Grade Bladder Cancer

“…There are various strains of BCG in the world, such as TICE, RIVM, Connaught and Tokyo 172 et cetera. Studies have demonstrated varying e cacies among these different strains [11][12][13] . As for the side effects, there were no signi cant variations observed due to different doses of BCG nor were there any differences noted based on the varying brands of BCG 14,15 .…”

“…There are various strains of BCG in the world, such as TICE, RIVM, Connaught and Tokyo 172 et cetera. Studies have demonstrated varying e cacies among these different strains [11][12][13] . As for the side effects, there were no signi cant variations observed due to different doses of BCG nor were there any differences noted based on the varying brands of BCG 14,15 .Because of the prevalence of BC, Connaught strain (ImmuCyst) had been widely utilized to treat NMIBC.Nonetheless, there was a worldwide shortage of Connaught strain so that we have to introduce TICE strain (Oncotice) in our institution.…”

Intermediate and high-risk non-muscle-invasive bladder cancer: an overview of epidemiology, burden, and unmet needs

“…Clinical trials have shown that BCG is safe and effective in reducing tumor recurrence and progression (104-109). Multiple BCG strains are available, which are considered to have equivalent efficacy and safety (11,17,(110)(111)(112).…”