INTRODUCTION AND OBJECTIVES: Patients with clinically node-positive (cN+) bladder cancer (BCa) form a biologically and prognostically diverse group. As systemic therapy reshapes management in this setting, this study examines oncological outcomes after radical cystectomy (RC) with or without perioperative systemic therapy. MATERIALS AND METHODS: We utilized a multicenter, retrospectively collected database of 1067 patients diagnosed with cTanyN+M0 BCa who underwent RC with lymphadenectomy with or without perioperative systemic treatment. Patients with cN1-2 disease and treated from 2006 and 2023 were included. Three-months landmark Kaplan-Meier curves were used to estimate the overall survival (OS). Three-months landmark competing risk cumulative incidence curves were used to estimate the cancer specific mortality (CSM). Multivariable Cox regression models (MCR) were used to assess the association of treatment and pathology response (complete response [pCR], partial response [pPR] and pN0) with any cause death and cancer specific death. RESULTS: A total of 589 patients met the inclusion criteria, with 189 (32%) receiving preoperative systemic treatment (PST) and 115 (20%) undergoing RC + adjuvant therapy (AT). Median follow-up was 32 months. Three-year OS was 69% for PST + RC, 55% for RC + AT, and 55% for RC alone. PST + RC (HR: 0.67, P = .042) was associated with a lower risk of all-cause mortality at MCR. The 3-year CSM was 28% for PST + RC, 38% for RC + AT, and 32% for RC alone. Achieving pCR (HR: 0.31, P = .004), pPR (HR: 0.35, P < .001), and pN0 (HR: 0.44, P < .001) was associated with significantly lower risks of both all-cause and cancer-specific mortality. CONCLUSIONS: Patients with cN+ BCa undergoing surgery show varied oncological outcomes. Those receiving PST and AT had longer OS, highlighting the importance of systemic therapy. The prognostic value of pCR, pPR, and pN0 supports the need for refined risk stratification to guide preoperative treatment and personalize care.

Clinica Luganese Moncucco Lugano Switzerland; Sant'Anna Clinic Swiss Medical Group Sorengo Switzerland; Belegarzt für Urologie Luzerner Kantonsspital Lucerne Switzerland

Department of Maternal Infant and Urologic Sciences Sapienza University Umberto 1 Polyclinic Hospital Rome Italy

Department of Surgical Sciences Division of Urology Torino School of Medicine Turin Italy

Department of Urology and Oncologic Urology Wrocław Medical University Wroclaw Poland

Department of Urology Careggi Hospital University of Florence Florence Italy

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna General Hospital Vienna Austria

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna General Hospital Vienna Austria; Department of Urology University of Texas Southwestern Dallas TX; Karl Landsteiner Institute of Urology and Andrology Vienna Austria; Department of Urology Weill Cornell Medical College New York NY; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Luzerner Kantonsspital Lucerne Switzerland

Department of Urology Medical University of Innsbruck Innsbruck Austria

Department of Urology Netherlands Cancer Institute Amsterdam Netherlands

Department of Urology Puigvert Foundation Autonomous University of Barcelona Barcelona Spain

Department of Urology Spedali Civili Hospital University of Brescia Brescia Italy

Department of Urology University of Tor Vergata Rome Italy

Department of Urology UROSUD La Croix Du Sud Hospital Quint Fonsegrives France

Division of Experimental Oncology Unit of Urology Urological Research Institute IRCCS Ospedale San Raffaele Milan Italy

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