Background/Objectives: Early-onset colorectal cancer (EOCRC) mortality has increased among younger adults in the United States, while rural-urban disparities in colorectal cancer outcomes remain persistent. This study evaluated EOCRC mortality trends among adults aged 25 - 44 years from 1999 to 2020 across the U.S. rural-urban continuum. Methods: We conducted a retrospective, population-based ecological study using the CDC WONDER Underlying Cause of Death database. Deaths were identified using ICD-10 codes C18-C20 for colorectal cancer as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 population were standardized to the 2000 U.S. standard population and stratified by 2013 National Center for Health Statistics urban-rural classification categories. Temporal trends were assessed using joinpoint regression to estimate annual percent change and average annual percent change (AAPC). Results: From 1999 to 2020, 37,459 EOCRC deaths occurred among U.S. adults aged 25 - 44 years. National AAMRs increased from 2.0 to 2.4 per 100,000, corresponding to an AAPC of +0.79% per year (95% CI: 0.63 - 0.95; p < 0.0001). Mortality increased across all urbanization categories, with predominantly linear trends. Nonmetropolitan counties had the highest absolute mortality rates, reaching 3.1 per 100,000 in both micropolitan and noncore areas by 2020. AAPCs ranged from +0.70% to +1.15% across urbanization categories, with no statistically significant pairwise differences. Conclusions: EOCRC mortality increased steadily across the U.S. rural-urban continuum, with persistently higher absolute mortality in nonmetropolitan populations. These findings support geographically targeted strategies to improve early detection, screening access, and colorectal cancer outcomes among younger adults.
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