Sequential Bacillus Calmette Guerin and electromotive mitomycin-C versus Bacillus Calmette Guerin alone for high-risk superficial bladder cancer: a prospective controlled study.

Background: Intravesical bacillus Calmette-Guèrin (BCG) and mitomycin C (MMC) are a theoretically attractive combination for the treatment of high risk superficial bladder cancer. We conducted a prospective, controlled study comparing BCG with sequential BCG + electromotive delivery MMC in patients with T1 bladder cancer. Methods: Following transurethral resection and multiple biopsies we randomized 175 patients with T1 bladder cancer into 2 groups. Group I received BCG 81 mg; 6 weekly instillations. Group II received sequential BCG and electromotive (intravesical electric current; 20 mA for 30 min.) MMC at weekly intervals thus: (BCG, BCG, MMC) x 3, totaling 6 BCG and 3 MMC instillations. Non responders received repeat courses at 3 months. All complete responders underwent maintenance regimens of monthly instillations. Group I: 10 BCG treatments. Group II: (MMC, MMC, BCG) x 3, treatments. Results: Group I vs Group II: median (IQR or 95% CI). Follow up (months): 64 (38–82) vs 71 (49–87); p = 0.054 Recurrence: 47% (36–58) vs 28% (19–39); p = 0.013 Months to Recurrence: 11 (6–19) vs 20 (16–33); p = 0.001 Progression: 20% (12–30) vs 14% (7–22); p = 0.312 Months to Progression: 17 (10–21) vs 46 (21–58); p = 0.002 % 5-years mortality by any cause: 11.6 (5.7–20.3) vs 4.5 (1.2–11.1); p = 0.099 % 5-years mortality by bladder cancer: 9.3 (4.1–17.5) vs 1.1 (0.02–6.1); p = 0.017 Side effects were numerous but mainly localized to the bladder. There were no treatment related deaths nor episodes of serious illness nor bladder contractures. Conclusions: Intravesical sequential BCG/electromotive MMC is superior to BCG alone in the treatment of high risk bladder cancer.