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

Abstract Background Although maintenance bacillus Calmette-Guerin (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 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-Guerin 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).