Multicenter phase 3 trial of single, early intravesical instillation of pirarubicin for prevention of bladder recurrence after radical nephroureterctomy for UTUC

The phase 3 JCOG1403 trial, at 44 centers in Japan, evaluated efficacy and safety of intravesical instillation of pirarubicin after radical nephroureterectomy for upper tract urothelial carcinoma (UTUC). Eligible patients aged 20-80 years with previously untreated, clinical stage 0a-III UTUC and ECOG performance status 0 or 1 were randomized 1:1 to receive either pirarubicin (30 mg in 30 ml via intravesical instillation, within 24 hours after surgery; n=153) or observation (n=151). Patients with pT3/T4 or pN+ status received adjuvant chemotherapy. The primary endpoint was relapse-free survival (RFS). Median follow-up was 4.3 years (IQR 3.4-5.1). 3-year RFS rate was 60% in the pirarubicin group and 47.0% in the observation group (HR 0.67; p=0.0066). The most common grade 3-4 adverse event was hematuria, wich occurred in four patients (3%) in the pirarubicin group and none in the observation group. No treatment-related serious adverse events or deaths were observed. The authors conclude that a single, postoperative pirarubicin instillation after radical nephroureterectomy is an efficacious treatment to reduce recurrence in UTUC, with manageable adverse events.