Objective: To investigate whether low-dose BCG treatment can reduce the side effects while maintaining efficacy for patients with NMIBC when compared with standard dose BCG treatment.
Methods: A comprehensive literature search of PubMed, EMBASE, CINAHL, LILACS and CENTRAL databases was conducted to identify relevant randomized controlled trials (RCT) or quasi-randomized controlled trials (qRCT) that have assessed the efficacy of low and standard dose BCG therapy for patients with NMIBC. Systematic review and meta-analysis were performed according to preferred reporting items for systematic reviews and meta-analysis criteria.
Results: Six RCTs and two qRCTs were eligible for meta-analysis. Low-dose BCG instillation was not inferior to reduce the risk of bladder tumor recurrence [hazard ratio (HR), 1.15; 95% confidence interval (CI), 1.00–1.31; P=0.05], meanwhile no difference was found regarding tumor progression (HR =1.08; 95% CI, 0.83–1.42; P=0.57). However, low-dose BCG provided a significantly lower incidence of overall side effects (RR =0.75; 95% CI, 0.60–0.94; P=0.01), systemic side effects (RR =0.57; 95% CI, 0.34–0.97; P=0.04), severe side effects (RR =0.52; 95% CI, 0.36–0.74; P=0.0003) and withdrawal due to BCG toxicity (RR =0.49; 95% CI, 0.26–0.91; P=0.02). In contrast, local side effects were comparable between low-dose and standard dose arms (RR =0.89; 95% CI, 0.73–1.08; P=0.24).
Conclusions: Low-dose BCG instillation significantly reduces the incidence of overall side effects, especially severe and systemic symptoms in patients with NMIBC, while the oncological control efficacy of low-dose BCG is not inferior to standard dose BCG. Further studies with stratification using different risk factors at randomization are required to assess whether the efficacy of low-dose BCG is comparable to standard dose BCG for different risk of patients.
