Introduction: The 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 Methods: We 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). Results: Among 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). Conclusion: In 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.
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)
Bignante G.;Wang L.;Antonelli A.;Porpiglia F.;Amparore D.;Checcucci E.;
2025-01-01
Abstract
Introduction: The 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 Methods: We 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). Results: Among 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). Conclusion: In 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.
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