Background
Phase 3, multicentre, open-label RCT (JCOG1403; jRCTs031180121) at 44 Japanese institutions. N=304 randomised (352 enrolled before surgery; 348 underwent radical nephroureterectomy [RNU]) with previously untreated clinical stage 0a–III upper tract urothelial carcinoma (UTUC), ECOG PS 0–1. Tested a single early postoperative intravesical instillation of pirarubicin (THP, an anthracycline) to prevent intravesical (bladder) recurrence after RNU.
Results
Interventions and follow up: Arm A: Single intravesical pirarubicin 30 mg in 30 mL, instilled within 24 h after RNU (n=153)
Arm B: Observation, no instillation (n=151)
Both arms: patients with pT3/T4 or pN+ disease received adjuvant chemotherapy
Primary endpoint: relapse-free survival (RFS), intention-to-treat
mFollow up: 4.3 years (IQR 3.4–5.1)
Results: RFS (3-year): 60.0% (95% CI 51.7–67.3) vs 47.0% (38.7–54.9); HR 0.67 (90.96% CI 0.50–0.88), P=.0066
Arm B: Observation, no instillation (n=151)
Both arms: patients with pT3/T4 or pN+ disease received adjuvant chemotherapy
Primary endpoint: relapse-free survival (RFS), intention-to-treat
mFollow up: 4.3 years (IQR 3.4–5.1)
Results: RFS (3-year): 60.0% (95% CI 51.7–67.3) vs 47.0% (38.7–54.9); HR 0.67 (90.96% CI 0.50–0.88), P=.0066
Adverse events
Grade 3–4 (most common): haematuria 3% (4 patients) vs 0%
Treatment-related serious AEs or deaths: none
Treatment-related serious AEs or deaths: none
Conclusions
A single, early postoperative intravesical pirarubicin instillation significantly improved relapse-free survival after radical nephroureterectomy for UTUC (HR 0.67), with minimal toxicity. This is the first phase 3 confirmation of single-dose intravesical chemotherapy in the post-RNU setting.
Key Limitations
RFS (which is driven largely by intravesical bladder recurrence) was the primary endpoint; an overall-survival benefit was not demonstrated. Open-label design with an observation (not placebo-instillation) control. Conducted entirely in Japan with pirarubicin, an anthracycline not widely available elsewhere, so extrapolation to mitomycin C or gemcitabine is inferred rather than tested. Higher-stage patients also received adjuvant chemotherapy, a potential confounder.
Clinical Context
A single postoperative dose of intravesical chemotherapy after RNU is already recommended by EAU guidelines to cut bladder recurrence, based largely on the ODMIT-C single-dose mitomycin C randomized trial and an earlier THP phase 2 study. JCOG1403 supplies the first dedicated phase 3, level-1 evidence for pirarubicin and reinforces intravesical instillation as standard practice after RNU for UTUC; where pirarubicin is unavailable, mitomycin C is the usual agent.