Prognostic Implications of Patients With Clinically Node Positive Bladder Cancer Undergoing Radical Cystectomy

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.