Long-term Outcome of Patients with Frequently Recurrent Non–muscle-invasive Bladder Carcinoma Treated with One Perioperative Plus Four Weekly Instillations of Mitomycin C Followed by Monthly Bacillus Calmette-Guérin (BCG) or Alternating BCG and Interferon-α2b Instillations: Prospective Randomised FinnBladder-4 Study

Abstract Background Recurrent TaT1 non–muscle-invasive bladder cancer (NMIBC) patients should be treated with immediate instillation of chemotherapy after transurethral resection of bladder tumour followed by instillation therapy. Objective To present long-term results of a study exploring the effect of initial mitomycin C (MMC) instillations followed by two types of immunotherapy for patients with frequently recurring NMIBC. Design, setting, and participants Between 1992 and 1996, 236 patients with frequently recurring TaT1 grade 1–2 NMIBC were enrolled in the prospective randomised multicentre FinnBladder-4 study. Intervention One perioperative plus four weekly instillations of MMC followed by monthly bacillus Calmette-Guerin (BCG) or alternating BCG and interferon (IFN)-α2b instillations for up to 1 yr. Outcome measurements and statistical analysis Primary end points were time to first recurrence and time to progression. Secondary end points were disease-specific mortality and overall survival. The principal statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model plus cumulative incidence and Kaplan-Meier analyses. Results and limitations The median follow-up was 10.3 yr (maximum: 19.8 yr) in the MMC-BCG group and 8.6 yr (maximum: 19.8 yr) in the MMC-BCG/IFN group. The probability of recurrence was significantly lower in the MMC-BCG group than in the MMC-BCG/IFN group (43% vs 78% at 10 yr and 45% vs 80% at 15 yr, respectively; hazard ratio: 2.86; 95% confidence interval, 1.98–4.13; p Conclusions Perioperative plus four weekly MMC instillations followed by monthly BCG, instead of alternating BCG and IFN-α2b instillations, significantly reduce long-term recurrence. Patient summary We demonstrated in non–muscle-invasive bladder cancer patients with exceptionally frequent recurrences that the risk of long-term recurrence was reduced from 78–80% to 43–45% if one perioperative plus four weekly mitomycin C instillations were followed by monthly bacillus Calmette-Guerin (BCG) instillations for 1 yr instead of alternating instillations of BCG and interferon-α2b. Trial registration The registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1992 and the last randomisation took place in 1996, before the current requirements concerning study registrations were implemented.