The optimal dose of intravesical bacillus Calmette-Guérin (BCG) for the treatment of non-muscle-invasive bladder cancer (NMIBC) is controversial. We investigated if induction therapy with low-dose BCG could achieve a similar complete response (CR) rate to standard-dose BCG, with less toxicity and higher quality of life (QOL).

After transurethral resection, patients with unresectable multiple NMIBC and/or carcinoma in situ were randomized to receive standard (80 mg) or low-dose (40 mg) BCG instillation induction therapy (weekly, 8 times). The primary endpoint was non-inferiority of low-dose BCG, with a null hypothesis of a 15% decrease in CR rate. Secondary endpoints were recurrence-free survival, progression-free survival, overall survival, patient compliance, adverse events and QOL using EORTC QLQ-C30.

In an intention-to-treat analysis of 166 patients, the CR rates for low-dose and standard-dose BCG were 79% (95% confidence interval [CI]: 0.70-0.88) and 85% (95% CI: 0.77-0.92), respectively. Dunnett-Gent analysis revealed that the null hypothesis of inferiority of low-dose BCG in terms of CR could not be rejected (p = 0.119). However, there were no significant differences between the groups in terms of recurrence, progression and overall survival. Low-dose BCG was associated with significantly less fever (p = 0.001) and micturition pain (p = 0.047) and significantly higher QOL scores for global QOL, role functioning and functional impairment.

The non-inferiority of low-dose BCG was not proven. However, low-dose BCG was associated with lower toxicity and higher QOL compared with standard-dose BCG in patients with NMIBC.