The Relationship of Clinical and Molecular Factors with Prognosis in Metastatic Colorectal Cancer

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Objective: Metastatic colorectal cancer (mCRC) remains a major global health challenge with highly variable survival outcomes.Both tumor-related and host-related factors contribute to prognosis, yet the combined influence of comorbidity burden, rat sarcoma (RAS) mutation status, and age has not been clearly established.This study aimed to evaluate the prognostic impact of the Charlson Comorbidity index (CCI), RAS mutation status, and age on overall survival (OS) and progression-free survival (PFS) in patients with mCRC.Methods: A retrospective analysis was conducted on 446 patients with histologically confirmed mCRC treated at a tertiary oncology center between 2010 and 2016.Demographic, clinical, and molecular data were collected.OS and PFS were analyzed using Kaplan-Meier estimates and compared with log-rank tests.Independent prognostic factors were determined using multivariate Cox proportional hazards models.Results: Among 446 patients, 56.7% had a CCI ≥7 and 38.6% were aged ≥65 years; 48.7% harbored RAS mutations.Higher comorbidity burden (CCI ≥7) was significantly associated with shorter OS and PFS (OS: 27.4 vs. 46.8months, p<0.001;PFS: 31.2 vs. 41.6 months, p=0.002).Multivariate analysis confirmed CCI ≥7 [hazard ratio (HR) =1.82, 95% confidence interval (CI) 1.31-2.52,p<0.001] and RAS mutation (HR =1.47, 95% CI 1.08-2.00,p=0.014) as independent predictors of poorer OS, whereas age lost significance after adjustment.Conclusion: CCI and RAS mutation status independently predict worse OS and PFS in mCRC.Incorporating comorbidity assessment into prognostic models may enhance personalized treatment strategies in real-world practice.

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