A retrospective study of differential prognostic factors in early-onset versus late-onset colorectal cancer: a comprehensive clinical and machine learning analysis

The incidence of early-onset colorectal cancer (EO-CRC; age <50 years) has been increasing worldwide. A total of 1,148 CRC patients were retrospectively analyzed and categorized into EO-CRC (n = 247) and LO-CRC (n = 901) groups. EO-CRC patients showed higher proportions of family history, concurrent polyps, and Programmed Cell Death Ligand 1 (PD-L1) expression >10%, whereas LO-CRC patients exhibited higher rates of hypertension, diabetes, and elevated carcinoembryonic antigen (CEA) levels. Although OS did not differ significantly between groups, their prognostic determinants varied markedly. In EO-CRC, distant metastasis, family history, Tumor, Node, and Metastasis (TNM) stage, PMS1 homolog 2, mismatch repair system component (PMS2), MutS Homolog 6 (MSH6), tumor size, concurrent polyps, and Ki-67 were major predictors. In LO-CRC, age, BRAF gene V600E mutation (BRAF V600E) mutation, elevated Carbohydrate antigen 19-9 (CA19-9), Ki-67, low hemoglobin, vascular invasion, MutL Homolog 1 (MLH1), and pathological type were significant contributors. This study suggests that EO-CRC and LO-CRC have fundamentally different prognostic determinants: the former emphasizes genetic susceptibility and tumor invasiveness, indicating that this group of patients may benefit from early genetic counseling, MMR/MSI testing, and immune checkpoint inhibitor therapy. The latter highlights age acquired molecular changes, and chronic systemic factors, supporting the inclusion of metabolic and geriatric assessments in routine tumor care.