Clinical factors are more strongly associated with prognosis than genetic alterations in early-onset colorectal cancer: a retrospective cohort study.

Early-onset colorectal cancer (EOCRC) is increasing globally and exhibits both aggressive clinicopathological features and distinct molecular characteristics. However, the relative contribution of clinical and genetic factors to prognosis remains unclear, particularly in underrepresented populations. A retrospective cohort study was conducted on 100 colorectal cancer (CRC) patients under 50 years of age, diagnosed and treated between January 2016 and December 2020, with follow-up up to 60 months or until death. Patients were stratified by patient characteristics, oncological features, and genetic mutation status to perform overall survival (OS) analysis. The mean OS was 49.8 months (95% CI: 46.4-53.2), with an estimated 5-year OS rate of 65.2%. The mean disease-free survival (DFS) was 50.1 months (95% CI: 46.2-53.9). In univariate analysis, factors significantly associated with OS included serum CEA level at diagnosis (p = 0.001), histological grade (p = 0.006), mode of surgery (emergency vs. elective) (p = 0.003), curative resection status (p < 0.001), disease stage (p < 0.001), mutations in the POL-MMR DNA repair gene group (p = 0.035), high mutation accumulation (p = 0.020), PIK3CA mutation (p = 0.036), and co-mutation of RAS/RAF and MMR genes (p = 0.011). However, when adjusted for disease stage, only patient and oncological factors remained associated with OS, including elevated CEA (HR = 2.33, 95% CI: 1.2-4.7, p = 0.018), poorly differentiated tumors (HR = 2.57, 95% CI: 1.2-5.7, p = 0.021), emergency surgery (HR = 3.50, 95% CI: 1.5-7.9, p = 0.003), and curative treatment (HR = 0.10, 95% CI: 0.05-0.2, p < 0.001). In EOCRC, clinical and treatment-related factors remained independently associated with overall survival after adjustment for disease stage, whereas the evaluated genetic variables did not retain statistical significance. These findings highlight the importance of clinical management strategies, while the prognostic value of genetic alterations requires further investigation.