Risk stratification in patients with pulmonary metastasis from colorectal cancer: prognostic utility of a composite inflammatory–nutritional index (N-CALLY index) — a retrospective cohort study

Abstract Background Pulmonary metastasis from colorectal cancer is associated with heterogeneous clinical outcomes, and reliable prognostic markers are needed for individualized risk stratification. The N-CALLY index, defined as the neutrophil-to-lymphocyte ratio (NLR) multiplied by the C-reactive protein-to-albumin ratio (CAR), is a composite marker that integrates two established components of the systemic inflammatory response. This study evaluated its prognostic value in patients who developed pulmonary metastasis after curative resection of primary colorectal cancer. Methods This retrospective single-center study analyzed 76 patients who developed pulmonary metastasis after curative resection of primary colorectal cancer between January 2008 and December 2022, after exclusion of one outlier case from an initial cohort of 77 consecutive patients. The N-CALLY index and other inflammatory, nutritional, and skeletal muscle indices were measured at the time of pulmonary metastasis diagnosis. Prognostic associations with overall survival were evaluated using receiver operating characteristic (ROC) analysis, Kaplan-Meier survival analysis, and Cox proportional hazards regression. Exploratory prognostic models with and without the N-CALLY index were compared using time-dependent ROC analysis and concordance indices. Results The N-CALLY index showed the highest area under the ROC curve among the systemic inflammatory and nutritional indices examined (AUC = 0.628), with a cohort-derived cut-off value of 0.03. An elevated N-CALLY index (≥ 0.03) was significantly associated with worse overall survival in univariate analysis (hazard ratio [HR], 3.524; 95% confidence interval [CI], 1.536–8.084; p = 0.003) and remained independently associated with worse overall survival in multivariable analysis (HR, 3.014; 95% CI, 1.285–7.068; p = 0.011). The prognostic model including the N-CALLY index showed higher time-dependent AUC values for 1-, 3-, and 5-year overall survival than the model without the N-CALLY index (0.730 vs. 0.619, 0.771 vs. 0.705, and 0.758 vs. 0.721, respectively), and the apparent C-index increased from 0.662 to 0.708 (optimism-corrected C-index, 0.645 to 0.686). Conclusions An elevated N-CALLY index at the time of pulmonary metastasis diagnosis was independently associated with worse overall survival, and its addition to a clinical prognostic model was associated with improved discrimination in this exploratory cohort. The N-CALLY index may therefore serve as an adjunctive prognostic marker to complement established clinicopathological factors, but should not be used as a stand-alone criterion for pulmonary metastasectomy or other treatment selection. Validation in independent external cohorts is required before clinical application.