The effect of age on the efficacy of maintenance bacillus Calmette-Guérin relative to maintenance epirubicin in patients with stage Ta T1 urothelial bladder cancer: results from EORTC genito-urinary group study 30911

Eur Urol. 2014 Oct;66(4):694-701. doi: 10.1016/j.eururo.2014.05.033. Epub 2014 Jun 16.

Abstract

Background: Although maintenance bacillus Calmette-Guérin (BCG) is the recommended treatment in high-risk non-muscle-invasive bladder cancer (NMIBC), its efficacy in older patients is controversial.

Objective: To determine the effect of age on prognosis and treatment outcome in patients with stage Ta T1 NMIBC treated with maintenance BCG.

Design, setting, and participants: A total of 957 patients with intermediate- or high-risk Ta T1 (without carcinoma in situ) NMIBC were randomized in European Organization for Research and Treatment of Cancer (EORTC) trial 30911 comparing six weekly instillations of epirubicin, BCG, and BCG plus isoniazid followed by three weekly maintenance instillations over 3 yr.

Outcome measurements and statistical analysis: Cox multivariate proportional hazards regression models were used to assess the relative importance of age for recurrence, progression, overall survival, and NMIBC-specific survival with adjustment for EORTC risk scores.

Results and limitations: Overall, 822 eligible patients were included: 546 patients in the BCG with or without INH arms and 276 in the epirubicin arm. In patients treated with BCG with or without INH, 34.1% were >70 yr of age and 3.7% were >80 yr. With a median follow-up of 9.2 yr, patients >70 yr had a shorter time to progression (p=0.028), overall survival (p<0.001), and NMIBC-specific survival (p=0.049) after adjustment for EORTC risk scores in the multivariate analysis. The time to recurrence was similar compared with the younger patients. BCG was more effective than epirubicin for all four end points considered, and there was no evidence that BCG was any less effective compared with epirubicin in patients >70 yr.

Conclusions: In intermediate- and high-risk Ta T1 urothelial bladder cancer patients treated with BCG, patients >70 yr of age have a worse long-term prognosis; however, BCG is more effective than epirubicin independent of patient age.

Patient summary: Intravesical bacillus Calmette-Guérin for non-muscle-invasive bladder cancer is less effective in patients >70 yr of age, but it is still more effective than epirubicin.

Trial registration: This study was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC 30911; http://www.cancer.gov/clinicaltrials/search/view?cdrid=77075&version=HealthProfessional&protocolsearchid=12442243#StudyIdInfo_CDR0000077075).

Keywords: Age; Bacillus Calmette-Guérin; Epirubicin; Instillation therapy; Non–muscle-invasive bladder cancer.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • BCG Vaccine / administration & dosage*
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology*
  • Carcinoma, Transitional Cell / surgery
  • Chemotherapy, Adjuvant
  • Cystectomy / methods
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Epirubicin / administration & dosage*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Risk Assessment
  • Survival Rate
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / surgery

Substances

  • BCG Vaccine
  • Epirubicin