A host-tumor interaction-based five-dimensional risk stratification system integrating immune surveillance, inflammation, nutrition, coagulation, and tumor burden for prognostic evaluation in stage III colorectal cancer

Objective Stage III colorectal cancer (CRC) exhibits substantial prognostic heterogeneity, underscoring the need for robust risk stratification tools. We aimed to develop and validate a novel five-dimensional (5D) score integrating immune surveillance, inflammation, nutrition, coagulation, and tumor burden to improve prognostic assessment in these patients. Materials and methods We retrospectively enrolled 338 patients with stage III CRC, who were randomly assigned to a discovery cohort (n=228) and a validation cohort (n=110). Preoperative peripheral blood biomarkers were detected before surgery to construct the 5D score. Patients were followed for three years to assess recurrence-free survival (RFS) and overall survival (OS). Kaplan-Meier analysis, Cox proportional hazards regression, and time-dependent receiver operating characteristic (ROC) curve analyses were performed to evaluate the prognostic performance of the score. Results Low levels of the combined lymphocyte-eosinophil-basophil immune- surveillance axis and prealbumin, together with elevated monocyte counts, fibrinogen, and the combined CEA-CA19–9 score, were significantly associated with inferior survival. The 5D score showed a strong stepwise association with both RFS and OS (plog-rank<0.001). Multivariate Cox regression analysis identified the 5D risk stratification system as an independent prognostic factor in both the discovery and validation cohorts and across age-stratified subgroups. Time-dependent ROC analyses demonstrated that the score achieved superior predictive performance for RFS and OS compared with biomarkers representing any single biological dimension. Furthermore, patients with low- and intermediate-risk scores appeared to benefit from the oxaliplatin-plus-capecitabine regimen, whereas those with ultra-high-risk scores experienced poor survival despite standard treatment. Conclusions The 5D score is a simple, cost-effective, and robust prognostic tool for patients with stage III CRC. By integrating complementary dimensions of host-tumor interactions, the 5D score may improve preoperative risk stratification and support individualized postoperative surveillance and treatment decisions. Prospective multi-center studies are warranted to further validate its clinical utility and biological significance.