Effective Dose and Adverse Effects of Maintenance Bacillus Calmette-Gue´Rin in Intermediate and High Risk Non-muscle Invasive Bladder Cancer: a Meta-analysis of Randomized Clinical Trial

Aim: to evaluate the effective dose and adverse effects of BCG doses. Methods: we searched published RCTs in Medline and Cochrane database before October 2013. Article using maintenance BCG after TUR in intermediate-high risk non-muscle invasive bladder cancer (NMIBC) and followed for effectiveness, local and systemic side effect are included. Low risk patients, other dose and MIBC were excluded. Results: meta-analysis of 6 clinical trials involving 2719 intermediate-high risk NMIBC patients showed recurrence rate in full dose (81 mg), low dose (27 mg) and very low dose (13.5 mg) were 33.3%, 34.7% and 30%, respectively. Meta-analysis of 2175 patients, 81 mg BCG was found to be superior to 27 mg in reducing tumour recurrences (RR 0.86; 95% CI 0.77-0.96, I2 = 0% and p=0.008). Meta-analysis of 544 patients, the effectiveness reducing tumour recurrences in 27 mg BCG was found to be superior to 13,5 BCG (RR 0.66; 95% CI 0.49-0.89, I2 = 8.8% and p=0.006). Systemic side effects were happened in 25%, 28.5%, and 15.5% in the doses 81.27 and 13.5 mg BCG, respectively. Low dose was superior to full dose in affecting systemic side effect (p=0,000) but no difference in affecting local side effect (p=0.137) in the meta-analysis of 1816 patients in 2 clinical trials. Conclusion: full dose BCG had superior outcome to reduce recurrences compared to low dose and very low dose. There were no significant differences between each dose in local side effect. However full dose regimen has higher systemic side effect compared to low and very low dose. Key words: Bacillus Calmette-Gue´Rin, dose and adverse effect, non-muscle invasive bladder cancer (NMIBC)