Weekly mitomycin C followed by monthly bacillus Calmette-Guerin or alternating monthly interferon-α2B and bacillus Calmette-Guerin for prophylaxis of recurrent papillary superficial bladder carcinoma

Purpose: We evaluated alternatives to bacillus Calmette-Guerin (BCG) monotherapy using a new combination of chemotherapy and immunotherapy for recurrent superficial bladder carcinoma. Materials and Methods: A total of 236 patients with frequently recurrent stage Ta or T1 bladder tumors were enrolled in our prospective, randomized, multicenter Finnbladder IV study. The initial mitomycin C instillation was instilled in all patients perioperatively after transurethral resection, followed by 4 weekly instillations of mitomycin C. Thereafter patients were randomized to receive monthly for up to 1 year BCG only or interferon-alpha 2b and BCG alternating monthly. Primary end points were time to initial recurrence, recurrence rate (number of recurrences per patient-year) and recurrence index (number of recurrent tumors per patient-year). Results: Of the 236 randomized patients 205 were eligible for study with a median overall followup of 30.7 months. Monthly BCG was superior to alternating monthly interferon-alpha and/or BCG with respect to time to initial recurrence (log rank test p <0.00001) as well as recurrence rate (0.4 versus 0.9, p <0.00001) and index (0.9 versus 3.0, p <0.00001). Side effects were limited. Conclusions: Monthly BCG given for up to 1 year preceded by perioperative and an additional 4 weekly mitomycin C instillations is a well tolerated mode of instillation therapy, providing excellent tumor control comparable to that of the best reported instillation regimens. No benefit was obtained by alternating interferon-alpha 2b with BCG.