Guopeng Wang, Xiang Dong, Xintong Zhang, Chengpeng Gu, Ting Hu, Fei Yang, Dong Wang, Yu Mao, Shangqing Ren
Preoperative systemic inflammatory biomarkers are individually associated with oncological outcomes following RNU for UTUC. Because each marker was pooled separately and the studies were clinically heterogeneous, the markers were not compared statistically and no ranking is implied; the findings are descriptive and hypothesis-generating. This meta-analysis of aggregate data did not assess predictive performance (discrimination, calibration, or clinical utility), and any SIRI-NLR combination remains a hypothesis requiring prospective, individual-patient-data validation before any clinical application.
BACKGROUND: Risk stratification remains challenging in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Preoperative systemic inflammatory biomarkers may provide prognostic information, but their relative clinical utility remains unclear.
METHODS: This systematic review and meta-analysis evaluated five commonly used preoperative inflammatory biomarkers-neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI)-in patients with UTUC treated with RNU. PubMed, Embase, Web of Science, and Cochrane Library were searched up to March 2026. Multivariate hazard ratios (HRs) for overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were pooled using random-effects models. Evidence certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS: Twelve retrospective studies comprising 7,346 patients were included. Elevated inflammatory biomarker levels were generally associated with worse survival outcomes across available studies. Significant associations with overall survival were observed for SIRI (pooled HR 2.09, 95% CI 1.27-3.44), NLR (pooled HR 1.97, 95% CI 1.74-2.22, I²=14.1%), MLR, SII, and PLR; comparable associations were seen for cancer-specific and recurrence-free survival. Each biomarker was analysed in a separate meta-analysis, and the contributing studies differed in design, populations, and cut-off values; the markers were therefore not compared statistically, and no inference regarding their relative prognostic performance is made.
CONCLUSION: Preoperative systemic inflammatory biomarkers are individually associated with oncological outcomes following RNU for UTUC. Because each marker was pooled separately and the studies were clinically heterogeneous, the markers were not compared statistically and no ranking is implied; the findings are descriptive and hypothesis-generating. This meta-analysis of aggregate data did not assess predictive performance (discrimination, calibration, or clinical utility), and any SIRI-NLR combination remains a hypothesis requiring prospective, individual-patient-data validation before any clinical application.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261307425, identifier CRD420261307425.