Single Early Pirarubicin After Nephroureterectomy Reduces Bladder Recurrence
Key Takeaways
- Higher 3-year relapse-free survival was observed with pirarubicin than with observation.
- JCOG1403 was a randomized phase 3 study across 44 institutes that enrolled adults aged 20-80 years with previously untreated clinical stage 0a-III disease and ECOG 0-1.
- Severe toxicity was limited, with hematuria the main grade 3-4 event and no treatment-related serious adverse events or deaths.
The phase 3 trial used two-stage registration across 44 institutes in the Urologic Oncology Study Group of the Japan Clinical Oncology Group. Eligible patients were 20-80 years old, had previously untreated clinical stage 0a-III upper tract urothelial carcinoma, and had an ECOG performance status of 0 or 1. First registration occurred before surgery; 352 participants were enrolled, 348 went on to radical nephroureterectomy, and 304 underwent second registration and randomization. Among these randomized participants, 226 were male and 78 were female. The randomized population therefore consisted of adults with previously untreated upper tract disease treated in a national cooperative group setting in Japan.
After radical nephroureterectomy, patients entered second registration and were randomly assigned 1:1 to pirarubicin or observation, with 153 assigned to pirarubicin and 151 to observation. Pirarubicin was given as 30 mg in 30 mL by intravesical instillation within 24 hours after surgery. The primary endpoint was relapse-free survival in the intention-to-treat population, and patients without an event were censored at last known alive and relapse-free status without imputation. Central web-based minimization was stratified by institution, clinical T stage, and urine cytology. Patients with pT3/T4 or pN-positive disease received adjuvant chemotherapy within the planned postoperative comparison.
Among randomized patients, 3-year relapse-free survival was 60.0% with pirarubicin and 47.0% with observation.
At a median follow-up of 4.3 years, with an IQR of 3.4-5.1 years, relapse-free survival separated over time between the randomized groups. The hazard ratio for relapse-free survival was 0.67 in the intention-to-treat analysis. The 90.96% confidence interval ranged from 0.50 to 0.88, and the reported p value was 0.0066. This analysis showed a between-group difference during follow-up in the randomized postoperative cohort. Overall, relapse-free survival favored pirarubicin over observation.
Severe toxicity was limited in the safety report. The most common grade 3-4 adverse event was haematuria, occurring in four patients in the pirarubicin group and in none in the observation group. This event represented 3% of patients who received pirarubicin. No treatment-related serious adverse events or deaths were observed. The postoperative pirarubicin comparison paired higher relapse-free survival with limited severe toxicity during follow-up.