A randomized trial comparing two different retention periods of intravesical pirarubicin instillation for intermediate risk non-muscule invasive bladder cancer (NMIBC) after transurethral resection.

Abstract

384 Background: Anthracyclines are recommended reagents for one immediate intravesical instillation after transurethral resection (TUR) and additional adjuvant instillation in intermediate risk NMIBC to reduce the risk of recurrence. Several studies have showed that Pirarubicin (THP), an anthracycline analogue, can rapidly penetrate tumor tissue after intravesical instillation. Therefore long instillation time (e.g. 120 min) may not be required for its prophylactic effect against recurrence without compromising its efficacy. Methods: This randomised, prospective, open-label trial intended to enroll 160 pts with primary NMIBC with intermediate risk based on EORTC criteria. Pts who seemed likely to be at intermediate risk were provisionally registered and then randomised into two groups with different intravesical THP retention times before TUR, (a) 30 min versus (b) 120 min. The registration was finally confirmed by pathology results of TUR. All registered pts received initial THP instillation within 24 hr after TUR and then intended to continue weekly repetitive THP instillation for a total of 9 treatments. Follow-up period is 4 years. Primary endpoint is change from baseline in quality of life measurements (e.g. OABSS and I-PSS), which were evaluated prior to each THP intravesical instillation. Secondary endpoint is recurrence-free survival. Results: 126 pts were enrolled for provisional registration. After excluding pts due to the result of pathology by TUR, 29 pts were assigned to group (a), and 26 pts to group (b). Although not statistically significant, there is a trend that group (a) is less prone to increase in OABSS after 3rd instillation compared to group (b). Log-rank test shows that there is no significant difference in recurrence-free survival between the groups during follow-up period (HR = 2.161, 95% C.I.: 0.4317-10.82, p= 0.3484). Conclusions: Shortening intravesical instillation period to 30 min has little effect on reducing the adverse effect of THP. However, it does not compromise the prophylactic effect on recurrence in intermediate risk NMIBC pts. Clinical trial information: UMIN000006861.