Baseline Neutrophil-to-Lymphocyte Ratio and Two-Year Incident Distant Metastasis in Stage I-III Lung Cancer: A...

Background: Distant metastatic relapse remains a major problem after treatment for lung cancer. We examined the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and newly documented distant metastasis within 2 years among patients without distant metastasis at baseline. Methods: We retrospectively screened 527 consecutive unique patients with a hospital diagnosis of lung cancer who were managed between 1 January and 31 December 2022; follow-up continued for 24 months after initial treatment (administrative cutoff, 31 December 2024). After hierarchical exclusions, 186 complete cases remained. The primary analysis included 148 patients with stage I-III disease and used record-based incident distant metastasis within 24 months, determined by comprehensive clinical assessment. Logistic regression estimated the association between continuous NLR and the endpoint before and after adjustment for age, sex, and clinical stage. Stage IV patients were retained only in a secondary analysis of the original heterogeneous composite endpoint. Results: Thirty-one out of 148 patients with stage I-III disease (20.9%) developed distant metastasis within 2 years. Mean pre-treatment NLR was 2.83 in patients with an event and 2.07 in those without an event. Each one-unit increase in NLR was associated with higher odds of distant metastasis in the unadjusted model (odds ratio [OR] 2.71, 95% confidence interval [CI] 1.65-4.45; p < 0.001) and after adjustment for age, sex, and stage (adjusted OR 2.70, 95% CI 1.60-4.57; p < 0.001). In the secondary full-cohort analysis, 49 of 186 patients met the heterogeneous composite endpoint. Conclusions: Higher pre-treatment NLR was associated with 2-year incident distant metastasis in this stage I-III cohort. The result does not establish causality or a clinically actionable cut point and requires prospective external validation.