Trends and projections of colorectal carcinoma mortality in U.S. adults, 1999–2050

Colorectal carcinoma (CRC) remains a major cause of cancer mortality in the United States (U.S.); however, contemporary long-term projections by demographic and geographic strata are limited. This study examined national colorectal cancer mortality trends from 1999 to 2025 and projected age-adjusted mortality rates (AAMRs) through 2050. We conducted an ecological time-series analysis of U.S. adults aged ≥ 25 years using Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death data. CRC-related deaths were identified by any mention of International Classification of Diseases, Tenth Revision codes C18-C20 on the death certificate. AAMRs per 100,000 population were calculated overall and stratified by sex, age group, race and ethnicity, urbanization, census region, state, and place of death. Joinpoint regression was used to estimate the annual percent change and average annual percent change. A demographically optimized ensemble forecasting model was used to project AAMRs from 2026 to 2050. From 1999 to 2025, 1,674,393 CRC-related deaths were recorded. Overall, the AAMR declined from 38.11 in 1999 to 23.14 in 2025 (average annual percent change, -1.99%; 95% confidence interval, -2.13 to -1.85; P < .001), but recent rates have stabilized. The mean AAMR was higher among men than women (34.13 vs 23.43) and higher in nonmetropolitan than metropolitan areas (32.43 vs 28.49). Non-Hispanic Black adults had the highest racial and ethnic burdens (37.45). Adults aged 25 to 44 years showed a significant increase in mortality (annual percent change, 1.13%; 95% confidence interval, 0.93 to 1.33; P < .001). Most deaths occurred at home (41.15% of deaths). The overall AAMR was projected to continue declining slowly, from 23.02 in 2026 to 21.56 in 2050, at a slower pace than the 1999 to 2016 decline. U.S. CRC mortality has declined substantially and is projected to continue declining slowly through 2050, rather than resume its earlier faster decline, with persistent sex, racial, rural, age, and geographic disparities. Targeted strategies are needed to improve screening completion, diagnostic follow-up, rural access, equity, and early-onset colorectal cancer detection.