Stage-dependent prognostic impact of age in colorectal cancer: A population-based SEER analysis

The prognostic association between age and colorectal cancer (CRC) survival may vary by stage. We analyzed adults with microscopically confirmed CRC diagnosed during 2004-2022 in the Surveillance, Epidemiology, and End Results database after excluding appendiceal primaries, death certificate-only/autopsy-only cases, and non-microscopically confirmed cases. Multivariable Cox models assessed age continuously, and age-by-stage interaction models compared patients aged 18-49 versus ≥ 50 years among those with known stage. The primary survival cohort included 454,216 patients; multivariable Cox models were fitted in 452,739 patients. Increasing age was associated with worse cancer-specific survival (CSS; HR 1.0279/year, 95% CI 1.0275-1.0284) and overall survival (OS; HR 1.0443/year, 95% CI 1.0440-1.0447). Age-by-stage interaction was significant for both endpoints. For CSS, the association of age ≥ 50 years was strongest in localized disease (HR 2.17, 95% CI 2.04-2.31) and attenuated in regional (HR 1.58, 95% CI 1.54-1.63) and distant disease (HR 1.41, 95% CI 1.38-1.44), with a similar pattern for OS. Older age was associated with worse CRC survival, but the magnitude of this association was stage-dependent.