Comparison of Three Schedules of Intravesical Epirubicin in Patients with Non–Muscle-Invasive Bladder Cancer

ObjectivesTo study the additive effect of either an early instillation or maintenance instillations of adjuvant intravesical epirubicin, as compared to the epirubicin “standard” treatment schedule only, in patients with non–muscle-invasive bladder cancer.MethodsPatients with intermediate- and high-risk urothelial cell carcinoma of the bladder, except carcinoma in situ, were randomised for adjuvant intravesical instillations with 50 mg epirubicin/50 ml NaCl for 1 h. Group 1 received 4 weekly and 5 monthly instillations (standard schedule), group 2 received the same schedule as group 1, but with an additional instillation <48 h after transurethral resection of bladder tumour (TURBT), and group 3 received the same scheme as group 1, but with additional instillations at 9 and 12 mo (maintenance schedule). Standard follow-up was 5 yr and consisted of cystoscopy, cytology, and registration of adverse events.ResultsA total of 731 patients were eligible for quasi intention-to-treat analysis. Side-effects were minimal for all treatment groups. After 5-yr follow-up, respectively, 44.4%, 42.7%, and 45.0% (log-rank test, p = 0.712) of the patients in groups 1, 2, and 3 were recurrence free, and 90.0%, 87.7%, and 88.2% (log-rank test, p = 0.593) of the patients, respectively, were progression free.ConclusionsIn the quasi intention-to-treat analysis there is no difference in the 5-yr recurrence-free period between the treatment groups, despite one instillation within 48 h of TURBT or two maintenance instillations up to 1 yr, in addition to the “standard” schedule.