Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Renal Cell Carcinoma: An Updated Systematic Review and Meta-analysis

Background: The neutrophil-to-lymphocyte ratio (NLR) has been proposed as a prognostic biomarker in renal cell carcinoma (RCC), and meta-analyses have confirmed an association between elevated NLR and poorer survival. However, these meta-analyses are limited by small sample sizes, search dates, insufficient evaluation of cancer-specific survival (CSS), and lack of subgroup analyses examining whether NLR's prognostic value differs by treatment, stage, region, or cut-off. Therefore, this updated systematic review and meta-analysis aimed to comprehensively evaluate the prognostic value of NLR in patients with RCC and to examine whether this association varies across treatment modalities, disease stages, geographic regions, and NLR cut-off values.

Methods: This updated meta-analysis was registered with PROSPERO (CRD42025637957) and followed PRISMA 2020. We searched PubMed, Embase, Web of Science, and Cochrane Library to August 2026. Eligible cohort studies enrolled confirmed RCC patients of subtype/stage, classified by NLR cut-off, and reported hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), CSS, recurrence-free survival (RFS), or disease-free survival (DFS). Quality and certainty were assessed using the Newcastle-Ottawa Scale (NOS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Pooled HRs were calculated using a random-effects model; heterogeneity quantified by Q and I². Subgroup analyses and meta-regression explored heterogeneity; funnel plots and Egger's test assessed publication bias.

Results: Twenty-six studies (6,041 patients) were included. Elevated NLR was associated with shorter OS (HR 1.93, 95% CI 1.56–2.39; I²=71%), RFS (HR 2.64, 95% CI 1.79–3.91; I²=35%), and DFS (HR 1.64, 95% CI 1.29–2.08; I²=82%), but not CSS (HR 1.62, 95% CI 0.51–5.13; I²=60%). Subgroup analyses showed NLR predicted OS/DFS in Asian/European but not American, and lost DFS prediction at cut-off ≥3. NLR effect was greatest in immunotherapy (HR 2.23) and significant in surgical/non-surgical subgroups. NOS scores were 7–8; incomplete confounder adjustment common. The certainty of evidence for the OS analysis was rated as very low according to GRADE. Sensitivity analyses confirmed the robustness of the pooled estimates, and Egger's test showed no significant publication bias for OS, RFS, or DFS.

Conclusions: This meta-analysis confirms NLR predicts poorer OS, RFS, DFS in RCC, but adds context-dependent evidence: not significant in Americans, weakened for DFS at higher cut-offs, and not for CSS. These findings refine NLR's utility and support cautious use as a risk-stratification biomarker, noting geography and thresholds. Future prospective studies with standardized cut-offs and confounder adjustment are needed.