Prognostic value of the neutrophil-to-lymphocyte ratio in patients with colorectal cancer undergoing chemotherapy: a systematic review and meta-analysis

Abstract

Colorectal cancer (CRC) remains a major global health burden. Chemotherapy is central to the management of advanced or metastatic disease and is also used in perioperative settings, but outcomes vary substantially. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive and readily available marker of systemic inflammation; its prognostic association in chemotherapy-treated CRC warrants focused evaluation. This study adhered to PRISMA guidelines and was registered with PROSPERO. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to July 15, 2025. Studies evaluating pretreatment NLR in relation to overall survival (OS) or a secondary progression- or recurrence-related time-to-event outcome, including progression-free survival (PFS), disease-free survival (DFS), or recurrence-free survival (RFS), in chemotherapy-treated CRC patients were eligible. Study screening, data extraction, and quality assessment were independently conducted by two reviewers. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup and leave-one-out sensitivity analyses were performed. Thirty-eight studies (41 cohorts; 11,346 patients) were included. Elevated pretreatment NLR was associated with poorer OS (HR = 1.68, 95% CI 1.54–1.84; P < 0.0001) and poorer progression- or recurrence-related survival (HR = 1.61, 95% CI 1.43–1.81; P < 0.0001). The direction of association was generally consistent across exploratory subgroups defined by treatment category, age, geographic region, and NLR cut-off. Leave-one-out analyses did not identify a single study that changed the direction of either pooled association. Between-study heterogeneity and evidence of small-study effects warrant cautious interpretation. Elevated pretreatment NLR was associated with poorer survival outcomes in chemotherapy-treated CRC. NLR may be a readily available prognostic biomarker, but heterogeneous populations, variable outcome definitions and cut-off values, inconsistent covariate adjustment, and possible small-study effects currently limit its use for clinical decision-making. Prospective validation and methodological standardization are required before routine application. https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420251136904.