Abstract
BACKGROUND: Although radical nephroureterectomy (RNU) with bladder cuff excision remains the gold standard treatment for upper tract urothelial carcinoma (UTUC), segmental ureterectomy (SU) may offer a nephron-sparing alternative. Studies comparing oncologic outcomes and renal functional outcomes between SU and RNU have yielded controversial, often conflicting results. Furthermore, investigations specifically involving ureteral UTUC patients in northern China are scarce. METHODS: We retrospectively enrolled 546 ureteral urothelial carcinoma patients (282 SU and 264 RNU cases) from three hospitals between October 2003 and September 2024 to assess overall survival (OS) and intravesical recurrence-free survival (IV-RFS) as oncologic outcomes, and to evaluate renal functional outcomes (preoperative, postoperative [2-month] and delta change in estimated glomerular filtration rate [eGFR] and serum creatinine [Scr]). The prognostic impact of surgical approach and clinicopathological variables were evaluated using Kaplan-Meier analysis with log-rank tests and Cox regression models. Significant predictors were incorporated into a validated nomogram for personalized 3-, 4-, and 5-year OS and IV-RFS probability estimation. Furthermore, eight machine learning algorithms (Lasso Cox, random survival forest [RSF], CoxBoost, generalized boosted regression modeling [GBM], support vector machine [Survival-SVM], eXtreme Gradient Boosting [XGBoost], supervised principal components [SuperPC], and partial least squares regression for Cox [plsRcox]) were implemented for OS and IV-RFS prediction modeling. Finally, we quantitatively pooled our cohort data with literature evidence retrieved from major databases (PubMed, Cochrane, Embase, Web of Science) up to 21 May 2025, to compare survival and renal function outcomes between the two procedures using Stata 14.0. Subgroup assessments and leave-one-out sensitivity analyses were performed to address potential confounding factors related to heterogeneity. RESULTS: Firstly, the multicenter retrospective cohort study revealed that SU was associated with reduced IV-RFS and was identified as a significant independent predictor of IV-RFS (HR = 1.48; P = 0.02). Meanwhile, there was no significant difference in OS between SU and RNU. Algorithm comparison confirmed optimal discriminative performance for IV-RFS (3-year AUC: 0.771, 4-year: 0.758, 5-year: 0.761) and OS (3-year AUC: 0.739, 4-year: 0.726, 5-year: 0.710). Decision curve analysis demonstrated the excellent clinical applicability of the nomograms for OS and IV-RFS, which enhanced model precision and clinical utility. Furthermore, in the meta-analysis, 21 studies including 31 293 patients were selected for inclusion, spanning publication years from 2010 to 2025. Regarding survival outcomes, although no statistically significant differences were observed in OS risk ( P = 0.696), CSS risk ( P = 0.765), or RFS ( P = 0.072) between patients receiving SU and those undergoing RNU, SU was associated with lower IV-RFS compared to RNU (HR = 1.21, P = 0.019). Subgroup analysis stratified by geographic region revealed significantly reduced OS with SU versus RNU in European cohorts (HR = 1.24, P = 0.001). Concerning renal functional outcomes, the SU group demonstrated significantly higher postoperative eGFR (WMD, 14.16 mL/min; P < 0.001) and greater delta change in eGFR (WMD, 11.78 mL/min; P < 0.001). CONCLUSION: SU achieves cancer-specific and overall survival comparable to RNU, even in high-grade ureteral UTUC, while significantly improving postoperative renal function. However, it necessitates multidisciplinary management of intravesical recurrence risk. Validation of molecular predictors and prospective trials in advanced disease are essential to further expand and validate the therapeutic landscape of SU.