Oncological outcomes of radical nephroureterectomy with or without lymphadenectomy and neoadjuvant therapy in cN+ UTUC: Insights from the ROBUUST registry.
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Passaro Francesco, Contieri Roberto, Tufano Antonio, Spena Gianluca, Bignante Gabriele, Vourganti Srinivas, Simone Giuseppe, Tuderti Gabriele, Wu Zhenjie, Wang Linhui, Gonzalgo Mark L, Nativ Omri Falik, Dehghanmanshadi Alireza, Rais-Bahrami Soroush, Ferro Matteo, de Cobelli Ottavio, Sundaram Chandru P, Sidhom Daniel A, Yoshida Takashi, Kinoshita Hidefumi, Ghodoussipour Saum, Fu Melinda, Porter James, Lee Randall, Correa Andres F, Ghoreifi Alireza, Moghaddam Farshad S, Djaladat Hooman, Puri Dhruv, Derweesh Ithaar H, Taylor Jacob, Margulis Vitaly, Li Taibo, Singla Nirmish, Eraky Ahmed, Mehrazin Reza, Minervini Andrea, Mari Andrea, Lambertini Luca, Fiori Cristian, Amparore Daniele, Checcucci Enrico, Porpiglia Francesco, Veccia Alessandro, Ditonno Francesco, Antonelli Alessandro, Abdollah Firas, Autorino Riccardo, Perdonà Sisto
Аннотация
METHODS: This retrospective study queried the ROBUUST registry, including 242 patients with cN + UTUC who underwent RNU between 2017 and 2024 across 17 institutions. Patients were stratified based on receipt of NAT and/or LND. Clinical, pathological, and follow-up data were analyzed. Primary endpoints included overall survival (OS) and cancer-specific survival (CSS), while metastasis-free survival (MFS) was a secondary endpoint. Survival outcomes were estimated using Kaplan-Meier curves and Cox regression analyses.
RESULTS: Among 2733 patients, 242 (8.8%) had cN + disease and were included. Median age was 69 years; 86% underwent LND and 27.6% received NAT. At pathology, 43.7% of LND patients were pN+, and NAT was associated with a higher rate of pN0 status (65% vs. 41%). After a median follow-up of 25.8 months, 12- and 24-month OS were 71% and 60%, respectively. On multivariable analysis, pN + status, tumor location, and ≥pT3 stage were associated with worse OS and CSS, while receipt of NAT was independently associated with improved OS (HR 0.52, p = 0.016) and CSS (HR 0.47, p = 0.020). LND was not independently associated with survival benefit. Sensitivity analysis showed improved OS in patients receiving both NAT and LND compared to LND alone.
CONCLUSIONS: In patients with cN + UTUC, NU as part of a multimodal strategy was associated with favorable short-term oncologic outcomes. Neoadjuvant therapy significantly improved survival, supporting its integration into the treatment paradigm for this high-risk group. Further prospective studies are warranted to optimize patient selection and treatment sequencing.