Real-world perioperative systemic treatment patterns and postoperative mortality in patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy in Japan: WAKKA-UTUC study

Abstract Background To characterize the longitudinal changes in perioperative systemic treatment patterns and postoperative mortality among Japanese patients with stage II–IV upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). Methods This retrospective observational study used a nationwide Japanese database to evaluate neoadjuvant chemotherapy (NAC) and adjuvant therapy (AT) before and after RNU. Treatment patterns, specific regimens, and 30- and 90-day postoperative mortality were analyzed descriptively across three periods: 2013–2017, 2018–2021, and 2022–2024. Results Among 6,165 patients included in the study, the use of AT without prior NAC increased from 25.7% in 2013–2017 to 30.0% in 2022–2024, and the proportion of patients who received any NAC increased from 9.8% to 17.1%, respectively. By 2022–2024, gemcitabine plus carboplatin emerged as the most widely used regimen for NAC and AT (6.5% and 15.2% of the overall study population during this period [n = 1,482], respectively). Adjuvant nivolumab was administered to 142 patients (9.6% of all patients undergoing RNU in 2022–2024), but most (n = 84) had not received prior NAC. Postoperative mortality remained stable across the study periods (30-day mortality: 0.0%–0.5%; 90-day mortality: 0.3%–2.0%), with no increase in mortality among patients who received NAC. Conclusions The use of perioperative systemic therapy for UTUC in Japan increased over the study period, with growing adoption of NAC, AT, and adjuvant nivolumab. Postoperative mortality remained stable, showing no notable association with NAC.