Prognostic Value of the Prognostic Nutritional Index in Patients with Locally Advanced Bladder Cancer Receiving...

Background and Objectives: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard of care for eligible patients with locally advanced bladder cancer (LABC). However, adjuvant chemotherapy (AC) remains widely used in real-world practice. Host-related inflammatory and nutritional biomarkers may also influence survival outcomes. This study aimed to compare survival outcomes between NAC and AC and to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS), with particular emphasis on the Prognostic Nutritional Index (PNI). Methods: This multicenter retrospective study included 262 patients with locally advanced bladder cancer. The median age was 66 years, and 84% of patients were male. Patients were treated with neoadjuvant chemotherapy followed by radical cystectomy or adjuvant chemotherapy after surgery between August 2021 and March 2025. The Prognostic Nutritional Index (PNI) was calculated using pretreatment laboratory values. ROC analysis was used to determine the optimal PNI cut-off for predicting mortality, and the derived threshold (49.97) was applied for stratification in all survival analyses. Survival outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox proportional hazards regression was used to identify independent prognostic factors. Results: Among 262 patients, 138 (52.7%) received NAC, and 124 (47.3%) received AC. Median follow-up was 33.6 months (95% CI: 29.4-37.8). No statistically significant differences in OS (p = 0.388) or PFS (p = 0.499) were observed between treatment groups. In univariate analyses, nodal stage, pathological complete response (pCR), and PNI were significantly associated with both OS and PFS. In multivariate analysis, low PNI (≤49.97) remained an independent predictor of mortality (HR 1.78, 95% CI 1.04-3.38; p = 0.044), while N3 nodal stage independently predicted disease progression (HR 5.92, 95% CI 1.06-32.84; p = 0.042). Conclusions: In this multicenter real-world cohort, nodal stage and systemic inflammatory-nutritional status were key determinants of prognosis in patients with locally advanced bladder cancer receiving perioperative chemotherapy. PNI emerged as an independent predictor of overall survival, suggesting that host-related biomarkers may improve prognostic stratification beyond traditional clinicopathological factors.