Colorectal Cancer in Younger and Elderly Patients: A Real-World Analysis from the Modena Cancer Center

Background: Early-onset colorectal cancer represents a growing global health challenge. Although differences between young and elderly patients are recognized, direct comparison of extreme age groups may further characterize their distinct clinical and therapeutic profiles. Methods: This is a retrospective, single-centre, observational study, comparing young patients (Group A: ≤50 years, n = 153) with elderly patients (Group B: ≥75 years, n = 533) during the period 1990–2025. Results: Group A presented higher rates of stage IV presentation (66.9% vs. 47.1%, p < 0.001), T4 tumors, N2 nodal involvement, distal tumor localization and synchronous metastasis (87.5% vs. 70.6%, p = 0.001), predominantly involving the liver and peritoneum. Younger patients received more intensive adjuvant and metastatic systemic treatment. The mOS was 52.8 months for Group A compared to 26.4 months for Group B (HR 2.29, 95% CI 1.57–3.54, p < 0.001) and DFS was longer in Group A (28.6 vs. 19.1 months; HR 2.26, 95% CI 1.55–3.29, p < 0.001). No statistically significant differences were observed in first- or second-line PFS between the cohorts. Conclusions: Early-onset colorectal cancer exhibits a more adverse clinicopathological profile. Younger patients showed longer overall and disease-free survival in this cohort, although these findings should be interpreted with caution given potential differences in treatment exposure, baseline fitness, comorbidity burden and the substantial temporal heterogeneity of the study period.