Age-Stratified Insights in Colorectal Cancer: A Four-Tier Analysis of Presentation, Treatment, and Outcomes

Abstract Background Colorectal cancer (CRC) exhibits significant age-related heterogeneity in tumor biology, clinical presentation, and treatment response. However, real-world, age-stratified data from the Middle East remain limited. Methods We conducted a retrospective cohort study of 761 patients with histologically confirmed colorectal adenocarcinoma treated at a tertiary cancer center in Saudi Arabia between 2015 and 2021. Patients were stratified into four age groups (≤ 40, 41–50, 51–64, ≥ 65 years). Clinicopathologic features, treatment patterns, and survival outcomes were compared using Kaplan–Meier and Cox regression analyses. Results Younger patients (≤ 40) were more likely to present with metastatic disease (61.4%), rectal primaries (57.6%), mucinous/signet ring histology, and peritoneal spread. Older patients (≥ 65) exhibited a higher prevalence of right-sided tumors (37.3%), BRAF mutations (9.7%), and functional impairment. Treatment intensity declined significantly with age, with older adults receiving fewer surgeries, adjuvant therapies, and later-line systemic regimens. Despite more aggressive disease at diagnosis, younger patients achieved superior median overall survival (38.2 vs. 24.8 months) and progression-free survival across all therapy lines. In multivariable analysis, age ≥ 65, ECOG ≥ 2, stage IV disease, right-sided location, absence of surgery, and BRAF mutation independently predicted worse survival. Conclusion This study highlights stark age-related disparities in CRC presentation, molecular profile, treatment delivery, and outcomes. Younger patients benefit from intensive therapy despite biologically aggressive disease, whereas older adults remain under-treated and experience poorer survival. These findings support the need for age-adapted, biology-informed CRC care and underscore the importance of integrating geriatric and molecular assessment into clinical decision-making.