The Impact of Dose Reduction of Bacillus Calmette-Guerin on Oncological Outcomes and Toxicity in Non-Muscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Bacillus Calmette-Guerin (BCG) is the standard adjuvant treatment for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) following transurethral resection of the bladder (TURB). However, the optimal dose, strain, and schedule of BCG remain unclear. OBJECTIVE: To evaluate the impact of BCG dose reduction on oncological outcomes and toxicity in patients with non-muscle invasive bladder cancer. METHODS: We performed a systematic review of the literature in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Selected studies were analyzed for Meta Analysis using PRISMA criteria. The study focused on disease recurrence, progression, and toxicity. We also compared the oncological outcomes of the different BCG strains. RESULTS: A total of 2963 patients in 13 randomized controlled trials were included. In recurrence analysis, we found a non-significant difference between the full dose and any dose reduction of BCG (RR = 1.17, [1.06-1.28], I2 = 0%, p = 0.7). In terms of progression, the difference was also non-statistically significant (RR: 1.12 [0.89 - 1.41], I2 = 0%, p = 0.93). In the toxicity analysis, there were more local (RR: 0.81 [0.67-0.99] I2 = 76%; p < 0.01) and systemic (RR: 0.53 [0.34-0.82] I2 = 83%; p < 0.01) side effects in the full dose group than in the dose reduction group. There were no statistically significant differences in oncological outcomes between the analyzed BCG strains. CONCLUSIONS: Dose reduction did not affect the oncological outcomes of patients with NMIBC who received adjuvant therapy with BCG. On the other hand, dose reduction showed a significant trend towards fewer systemic and local side effects. Further studies comparing oncological and toxicity outcomes using different strains are needed.