Combined neoadjuvant and adjuvant therapy versus adjuvant therapy in high-risk upper tract urothelial carcinoma: a propensity matched multicenter analysis (ROBUUST 2.0 International Collaborative Group)

IntroductionThe efficacy of combined neoadjuvant and adjuvant therapy (CNAT) in upper tract urothelial carcinoma (UTUC) remains unclear despite its demonstrated potential in bladder urothelial carcinoma. High-risk features- clinical stage >= T3, node-positive disease, multifocality, high-grade pathology, hydronephrosis, and large tumor size - are associated with poor prognosis in UTUC. We investigated the oncological outcomes of CNAT versus adjuvant therapy (AT) alone in high-risk UTUC patients.Materials and MethodsWe analyzed perioperative data from 2433 patients with UTUC (2015-2023) across 17 centers in the US, Europe, and Asia. Propensity score matching was performed using preoperative clinical T and N stages. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and metastasis-free survival (MFS).ResultsAmong 285 high-risk UTUC patients, 76 matched patients (38 CNAT, 38 AT) were analyzed after matching, with a median follow-up of 15 months. CNAT and AT groups had comparable oncological outcomes: 2-year OS (72.9% vs. 71.8%; p = 0.89), CSS (76.7% vs. 75.3%; p = 0.92), RFS (30.1% vs. 39%; p = 0.97), or MFS (45.5% vs. 44.7%; p = 0.91), respectively. Cox regression showed no significant survival benefit of CNAT over AT after adjusting for clinical and pathological factors (HR for OS: 1.06; p = 0.9).ConclusionIn this large multicenter international cohort, our findings suggest that CNAT does not provide a clear advantage over AT alone in patients with high-risk UTUC. Prospective randomized trials are needed to clarify the role of multimodal therapy in UTUC management.