Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of a randomized trial with epirubicin comparing short-term versus long-term maintenance treatment

PURPOSE: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for non-muscle-invasive bladder cancer after transurethral resection. We evaluated the optimal duration of EPI instillation in a multi-institution prospective randomized clinical study. METHODS: Between June 1995 and May 1998, a total of 125 patients with superficial bladder cancer (transitional cell carcinoma grade 1 or 2) were enrolled in this study, and 102 patients were fully evaluated for recurrence. Two protocols for intravesical therapy (arm A - 30 mg EPI/30 ml saline 19 times over 1 year; arm B - 30 mg EPI/30 ml 12 times over 5 months) were established. Instillations were given every week for 4 weeks and then every 2 weeks for 4 months in arm B. After 5 months of treatment, maintenance was performed with seven further instillations (one every month for 7 months) in arm A. The analyzed background factors were the therapeutic method, gender, history (primary or recurrent tumor), stage (T classification), grade, number of tumors, and tumor size. RESULTS: There were no significant differences in the analyzed background factors between the two arms, and there were no serious side effects in the study. In an intent-to-treat analysis, the overall 3-year recurrence-free survival rates were 48.5% in arm A and 55.1% in arm B. The difference between the two groups was not significant. CONCLUSIONS: This analysis indicated that extended prophylactic maintenance instillation of EPI was not significantly effective in reducing bladder cancer recurrence.