Maintenance bacillus Calmette-Guerin in high-risk nonmuscle-invasive bladder cancer - How much is enough?

BACKGROUND. Intravesical bacillus Calmette-Guerin (BCG) immunotherapy is effective in preventing recurrence and progression in nonmuscle-invasive bladder cancer but the dosing schedule and duration of treatment remain empirical. The outcome of BCG therapy was prospectively evaluated on patients according to the number of maintenance cycles received. METHODS. Between 1997 and 2002, 111 patients with nonmuscle-invasive bladder cancer at high risk of recurrence and progression underwent transurethral resection followed by intravesical instillations of BCG. After an induction treatment of 6 weekly instillations, patients were scheduled to receive a 3-weekly maintenance treatment at the 3rd, 6th, 12th, 18th, 24th, 30th, and 36th month. At each visit a clinical assessment was obtained. RESULTS. Over a median clinical follow-up of 31 months, 43% of patients experienced recurrence and 8.1% progressed to muscle-invasive disease or metastasis. only 1 patient received all scheduled instillations. Patients who received at least 3 maintenance BCG cycles had a significantly reduced risk of recurrence (hazard ratio [HR] = 0.23, P =.0064, adjusted for gender, age, and stage) compared with patients receiving only induction BCG. Twelve months after the end of maintenance, the estimated Kaplan-Meier recurrence-free survival was 89% for patients who received at least 3 maintenance BCG cycles, 67% for those who received 2 maintenance BCG cycles, and 41% for those who received only the induction BCG or I maintenance cycle (P = .0003). CONCLUSIONS. The results of this study suggest that a minimum of 3 cycles of maintenance BCG is required to significantly reduce the recurrence rate. It also suggests that more cycles may result in further improvements but the benefits may be outweighed by increasing side effects in some patients.