Sustained prophylactic effect of intravesical bacille Calmette-Guerin for superficial bladder cancer: A smoothed hazard analysis in a randomized prospective study

Objectives. A previous meta-analysis had revealed that intravesical chemotherapy was effective in reducing the recurrence of superficial bladder cancer only in the early phase, the phase thought to be caused by tumor cell implantation and/or residual tumor cells. To ascertain the sustained prophylactic effect of intravesical bacille Calmette-Guerin (BCG) after transurethral resection of bladder tumor (TURBT), we compared the estimation of the duration of the effect with that of doxorubicin. Methods. Eighty eligible patients with superficial bladder cancer (Stage Ta or T1, grade 1 or 2) were included. Patients were randomly allocated into two groups: the BCG group (six weekly instillations of 80 mg BCG [Tokyo 172 strain]) and the doxorubicin group (17 instillations of 20 mg doxorubicin). A comparison between the smoothed hazards of tumor recurrence was performed using a kernel function method. Results. All 80 patients (40 each in the BCG and doxorubicin groups) were compared. The median follow-up period was 667 days (range 64 to 1607). The risk of recurrence was significantly lower in the BCG group than in the doxorubicin group (P = 0.017, log-rank test). A smoothed hazard curve depicting the reduced risk of recurrence in the BCG group suggested that BCG is not only efficacious in the early phase of recurrence (up to 500 days after TURBT), but also in the late phase, and the latter is thought to include second primary tumors (new tumors). Conclusions. BCG instillation may prevent tumor recurrence caused by both tumor cell implantation and second primary tumors.