Abstract
BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC), defined as diagnosis at age ≤50 years, is rising globally. Despite younger age and presumed clinical fitness, EOCRC often presents at advanced stages and displays distinct biologic and treatment profiles. METHODS: We conducted a retrospective cohort study of patients aged ≤50 years with histologically confirmed colorectal adenocarcinoma treated at a tertiary cancer center in Saudi Arabia from 2015 to 2021. Clinical, pathologic, molecular, and treatment data were extracted. Survival outcomes were analyzed using Kaplan-Meier methods, and prognostic factors were assessed via Cox regression models. RESULTS: Among 97 patients (mean age 43 ± 5 years; 56% male), 34% presented with metastatic disease and 75% had left-sided or rectal tumors. Obesity was prevalent in 24% of cases. Surgical resection was performed in 79% of patients, of whom 47% received adjuvant chemotherapy. First-line systemic therapy was administered in 39%, but attrition limited progression to subsequent lines. Median overall survival (OS) was 20 months (interquartile range [IQR], 11-30). Progression-free survival (PFS) declined from 8 months in first-line to 4 months in third-line therapy. On multivariable analysis, obesity was independently associated with worse OS (hazard ratio [HR] 6.63, p = 0.035). CONCLUSION: Despite favorable performance status, EOCRC frequently presents with advanced disease and limited systemic therapy durability. Obesity emerged as an independent adverse prognostic factor. These findings reinforce EOCRC as a biologically distinct entity, underscoring the need for tailored screening strategies, early intensification of therapy, and molecularly guided care.