Prognostic Significance of the CALM Index in Surgically Resected Non-Small Cell Lung Cancer

Background: Anatomical staging is often insufficient for predicting outcomes in stage I-IIIA non-small cell lung cancer (NSCLC) patients after curative resection due to inherent prognostic variability. In this study, we evaluated the prognostic value of the C-reactive protein–albumin–lymphocyte–monocyte (CALM) index as an integrative biomarker for overall survival (OS). Methods: This retrospective study included 533 patients with stage I-IIIA NSCLC. We assessed the association between the CALM index and OS using multivariable Cox proportional hazards models, adjusted for established clinicopathological factors. We employed LASSO-penalized regression to optimize variable selection and ensure model stability. Comprehensive performance metrics were calculated, including Harrell’s C-index, integrated area under the curve (iAUC), integrated discrimination improvement (IDI), and decision-curve analysis (DCA). Results: The CALM index was identified as a stable, independent predictor of OS across both conventional and LASSO-penalized models. The final multivariable model incorporated the CALM index alongside age, pathological stage, American Society of Anesthesiologists status, pleural invasion, and the modified Shine–Lal index. Incorporation of the CALM index significantly enhanced model discrimination and risk reclassification at 3 and 5 years, while consistently increasing net clinical benefit across a wide range of threshold probabilities. Conclusions: The CALM index is a biologically plausible, robust, and readily accessible prognostic biomarker that provides incremental prognostic information beyond established factors in patients with resected stage I-IIIA NSCLC. Its integration into postoperative assessment offers a framework for refined prognostic stratification and more individualized clinical decision-making.