Abstract
BACKGROUND: The management of upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) is hampered by heterogeneous outcomes and a lack of robust, integrative biomarkers. The Prognostic Nutritional Index (PNI), reflecting both nutritional status and systemic immunity, has emerged as a prognostic tool in various cancers, but its utility in UTUC remains underexplored. OBJECTIVE: To comprehensively evaluate the prognostic value of preoperative PNI and to develop a validated nomogram for predicting progression-free survival (PFS) in UTUC patients undergoing RNU. METHODS: In this retrospective cohort study, 200 consecutive UTUC patients treated with RNU (2016–2020) were analyzed. The PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per μL). Receiver operating characteristic (ROC) curve analysis determined the optimal PNI cut-off. Survival analyses were performed using Kaplan–Meier and Cox proportional hazards models. A nomogram integrating independent predictors was developed and subjected to internal validation with bootstrapping, assessing discrimination, calibration, and clinical utility. RESULTS: The optimal PNI cut-off was 46.0, demonstrating high predictive accuracy for recurrence (area under the curve [AUC] = 0.866). Patients with low PNI (< 46.0) had significantly inferior PFS (median PFS: 32 vs. 58 months; log-rank P = 0.002). Multivariate analysis identified low PNI (Hazard Ratio [HR] = 1.96, 95% Confidence Interval [CI]: 1.33–2.88, P < 0.001), tumor size ≥ 3 cm (HR = 1.84, 95% CI: 1.06–3.20, P = 0.030), multifocality (HR = 1.80, 95% CI: 1.09–2.97, P = 0.021), high-grade pathology (HR = 1.68, 95% CI: 1.03–2.73, P = 0.037), and advanced T stage (pT3/T4) as independent predictors of poor PFS. The resultant nomogram exhibited good discriminative ability, with an AUC of 0.903 for predicting 3-year PFS, and provided a positive net benefit on decision curve analysis. CONCLUSION: Preoperative PNI may serve as a potent, independent prognostic factor for UTUC. The integrated nomogram demonstrates good predictive accuracy and facilitates personalized risk assessment, potentially guiding adjuvant therapy decisions and postoperative surveillance strategies. The modifiable nature of PNI also opens avenues for nutritional and immunomodulatory interventions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-026-04676-z.