Neutrophil-to-lymphocyte ratio as a prognostic biomarker in lung cancer patients treated with PD-1/PD-L1 inhibitors: A systematic review and meta-analysis

Lung cancer (LC) continues to be a leading cause of cancer-related mortality, highlighting the need for reliable and accessible biomarkers to identify patients at higher risk of poor outcomes during immunotherapy. This systematic review and meta-analysis aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with LC receiving programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. Comprehensive searches were conducted in the Cochrane Library, Web of Science, Embase, and PubMed up to February 13, 2025, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS), and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated employing random-effects models. A total of 49 studies encompassing 7,897 patients were analyzed. Elevated NLR was significantly associated with shorter overall survival (OS) (HR = 1.92, 95% CI: 1.70-2.17) and progression-free survival (PFS) (HR = 1.66, 95% CI: 1.48-1.87). These associations remained consistent across most subgroups and sensitivity analyses, including those focused on non-small cell lung cancer (NSCLC) patients with pretreatment NLR measurements. However, it is important to consider heterogeneity and potential publication bias regarding PFS when interpreting these findings. Elevated NLR is indicative of poorer survival outcomes in patients with LC treated with PD-1/PD-L1 inhibitors and may function as a practical prognostic biomarker. Nonetheless, prospective studies with standardized cutoff values are necessary prior to routine clinical implementation.