An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guérin for non-muscle-invasive bladder cancer

Eur Urol. 2009 Aug;56(2):247-56. doi: 10.1016/j.eururo.2009.04.038. Epub 2009 Apr 24.

Abstract

Background: Patients with non-muscle-invasive bladder cancer with an intermediate or high risk need adjuvant intravesical therapy after surgery. Based largely on meta-analyses of previously published results, guidelines recommend using either bacillus Calmette-Guérin (BCG) or mitomycin C (MMC) in these patients. Individual patient data (IPD) meta-analyses, however, are the gold standard.

Objective: To compare the efficacy of BCG and MMC based on an IPD meta-analysis of randomised trials.

Design, setting, and participants: Trials were searched through Medline and review articles. The relevant trial investigators were contacted to provide IPD.

Measurements: The drugs were compared with respect to time to recurrence, progression, and overall and cancer-specific death.

Results and limitations: Nine trials that included 2820 patients were identified, and IPD were obtained from all of them. Patient characteristics were 71% primary, 54% Ta, 43% T1, 25% G1, 58% G2, and 16% G3, and 7% had prior intravesical chemotherapy. Based on a median follow-up of 4.4 yr, 43% recurred. Overall, there was no difference in the time to first recurrence (p=0.09) between BCG and MMC. In the trials with BCG maintenance, a 32% reduction in risk of recurrence on BCG compared to MMC was found (p<0.0001), while there was a 28% risk increase (p=0.006) for BCG in the trials without maintenance. BCG with maintenance was more effective than MMC in both patients previously treated and those not previously treated with chemotherapy. In the subset of 1880 patients for whom data on progression, survival, and cause of death were available, 12% progressed and 24% died, and, of those, 30% of the deaths were due to bladder cancer. No statistically significant differences were found for these long-term end points.

Conclusions: For prophylaxis of recurrence, maintenance BCG is required to demonstrate superiority to MMC. Prior intravesical chemotherapy was not a confounder. There were no statistically significant differences regarding progression, overall survival, and cancer-specific survival between the two treatments.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Administration, Intravesical
  • Antibiotics, Antineoplastic / administration & dosage*
  • BCG Vaccine / therapeutic use*
  • Humans
  • Mitomycin / administration & dosage*
  • Randomized Controlled Trials as Topic
  • Time Factors
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*

Substances

  • Adjuvants, Immunologic
  • Antibiotics, Antineoplastic
  • BCG Vaccine
  • Mitomycin