The role of neoadjuvant systemic therapy for high grade upper tract urothelial carcinoma: Results from the upper tract collaborative network (UCAN).

Introduction: Utilization of neoadjuvant systemic therapy (NAT) prior to radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is inconsistent, and optimal patient selection for NAT is unclear. The purpose of this study was to evaluate the clinical benefit of NAT in high grade UTUC undergoing RNU.

Materials and methods: The UTUC Collaborative Network (UCAN) identified patients who underwent RNU for high grade UTUC between 2000 and 2022. NAT was examined as a primary exposure. NAT was defined as any systemic therapy prior to RNU. The outcomes of interest were extra-urothelial recurrence free survival (euRFS), cancer-specific survival (CSS), and overall survival (OS).

Results: Among 461 patients meeting criteria, 51.2% received NAT. At a median follow-up of 2.9 years, 24.1% experienced extra-urothelial recurrence at a median of 2.4 (1.0-5.2) years. On multivariable Cox proportional hazards models, NAT was associated with improved CSS (HR 0.58; 95% CI 0.36-0.94). In clinically node negative patients receiving NAT, Kaplan-Meier analysis showed improved euRFS (P = 0.01), cancer-specific survival (P = 0.002), and overall survival (P = 0.002). A statistically significant benefit was not observed for clinically node positive patients receiving NAT in euRFS (P = 0.667), CSS (P = 0.200), or OS (P = 0.313).

Conclusions: NAT was associated with improved survival outcomes in patients with clinically node negative disease. These benefits were not consistently observed in those with clinically node positive disease, although there was trend toward improved outcomes on multivariable Cox models. Further prospective investigations regarding risk stratification and multimodal management are needed in patients with high grade UTUC.