Mean Corpuscular Volume as a Prognostic Marker in Patients with Non-Small Cell Lung Cancer Undergoing Surgical Resection: A Cohort Study

Background and Objectives: Anatomical stage alone inadequately reflects outcome variability in resected non-small cell lung cancer (NSCLC). Although systemic inflammation-based biomarkers have demonstrated prognostic utility, the clinical significance of erythrocyte-derived indices, particularly the mean corpuscular volume (MCV), remains poorly defined in resected NSCLC. This study investigated the prognostic significance of preoperative MCV and determined whether its integration with the Noble and Underwood (NUn) score improves survival prediction. Methods: We retrospectively analyzed patients with stage I–IIIA NSCLC who underwent complete surgical resection. The association between preoperative MCV and overall survival (OS) was assessed using multivariate Cox proportional hazards regression analysis. To elucidate the determinants of MCV, machine-learning-based interpretability analyses, including least absolute shrinkage and selection operator regression and SHapley Additive exPlanations, were applied. A composite NUn–MCV index was subsequently constructed and incorporated into prognostic models. Model performance was evaluated using multiple complementary metrics, including the concordance index and integrated area under the curve. Results: Preoperative MCV was independently associated with OS after adjusting for established clinicopathological covariates. Mechanistic analyses demonstrated that MCV variability was predominantly driven by intrinsic erythrocyte indices rather than by systemic inflammatory or clinical parameters. The composite NUn–MCV index provided greater prognostic value than that of the NUn score or MCV alone. Across all comparative analyses, the fully adjusted model incorporating the NUn–MCV index yielded the greatest improvement in survival discrimination, exceeding that achieved by a clinically adjusted model without NUn–MCV, alternative biomarker-based models, and pathological staging alone. Conclusions: Preoperative MCV is an independent prognostic determinant in patients with stage I–IIIA NSCLC. Integrating MCV with the NUn score to form the NUn–MCV index enhances prognostic discrimination using routinely available laboratory parameters. This composite biomarker may enable more refined risk stratification and support individualized postoperative management in resected NSCLC.