Trends and disparities in colorectal cancer mortality in the United States, 1999–2024, with projections up to 2048: an epidemiological time-series analysis and modeling study

Colorectal cancer (CRC) remains a critical public health challenge in the USA, marked by a complex epidemiological shift. Despite historical improvements, the rising incidence among younger adults and an aging population necessitate a comprehensive evaluation of long-term mortality trends and demographic disparities to optimize future cancer control and health equity. Utilizing national mortality data from the CDC WONDER database between 1999 and 2024, we systematically evaluated both age-adjusted mortality rates (AAMRs) and total death counts, stratified by age, sex, race, and geographic region. Temporal trends were assessed using Joinpoint regression analysis to calculate the average annual percent change. Furthermore, a time-series analysis using autoregressive integrated moving average (ARIMA) models was employed to forecast trends and total death counts for the period 2025 through 2048. Between 1999 and 2024, the USA experienced a significant decline in CRC AAMRs, whereas the total number of deaths in 2024 showed only a slight decrease compared with 1999. Subgroup analysis revealed that while both sexes recorded standardized rate reductions, men persistently maintained higher AAMRs than women and exhibited a slight increase in total death counts over the study period. Age-specific analysis highlighted a critical epidemiological shift, as mortality rates have risen significantly among individuals younger than 54 years in recent years, while the historical decline in mortality among older adults has notably slowed during the same period. Regarding race and ethnicity, non-Hispanic Black populations exhibited the highest mortality rates, while the Hispanic population experienced a staggering 159.74% surge in total death counts. Geographically, mortality rates were higher in the South and Midwest than in the West and Northeast, indicating substantial regional and state-level heterogeneity. Looking forward, ARIMA models project a significant directional divergence for the period 2025 through 2048: despite a continued decline in AAMRs, model-based projections suggest that the annual number of CRC deaths will reverse the modest decline observed from 1999 to 2024 and progressively escalate to an estimated 64,855 by 2048. While the significant decline in AAMRs reflects historical progress, the projected escalation in total death counts through 2048 highlights growing demographic challenges. Future cancer control strategies must sustain current screening successes, expand early detection by lowering the screening age for younger adults, and prepare healthcare systems for the rising volume of CRC deaths.