Projected mortality rates and total deaths from gastrointestinal malignancies in the United States, 1999 to 2023

National mortality from gastrointestinal malignancies has declined, but aggregate trends may obscure demographic and geographic differences. We evaluated trends through 2023 and conditional forecasts of rates and deaths based on historical time-series patterns. We conducted an ecological time-trend study of United States residents aged 25 years or older whose underlying cause of death was a selected gastrointestinal malignancy (International Classification of Diseases, 10th Revision, C16-C20). We combined nonoverlapping records from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Underlying Cause of Death modules for 1999 to 2020 and 2021 to 2023. Age-adjusted mortality rates (AAMRs) were standardized to the 2000 United States. population; age-specific crude rates were used for age groups. Joinpoint regression estimated annual percent changes (APCs) and average annual percent changes (AAPCs). Autoregressive integrated moving average models generated conditional forecasts for 2024 to 2046 and were assessed by rolling-origin 1-year-ahead validation. Among 1,643,934 deaths, annual deaths decreased from 70,375 in 1999 to 66,390 in 2023, while the AAMR declined from 39.80 (95% confidence interval [CI]: 39.50-40.09) to 24.30 (95% CI: 24.11-24.48) per 100,000 (AAPC = -2.08; 95% CI: -2.29 to -1.86). Joinpoint regression identified slope changes in 2011 and 2020; the APCs were -2.78 in 1999 to 2011, -1.80 in 2011 to 2020, and -0.10 in 2020 to 2023. The age-specific rate increased among adults aged 35 to 44 years (AAPC = 0.60; 95% CI: 0.38-0.82). Mortality decreased for colon and stomach cancers but increased for small intestine and rectosigmoid junction cancers. In ecological population-level comparisons, the non-Hispanic Black population had the highest ethnicity-specific AAMR in 2023 (32.46; 95% CI: 31.78-33.15), and the nonmetropolitan AAMR exceeded the metropolitan AAMR in 2020 (27.48 vs. 23.72). Forecasts indicated declining AAMRs but increasing deaths. Combined mortality from C16 to C20 malignancies declined overall, although temporal trends varied across population subgroups, geographic areas, and individual cancer sites. The projected divergence between AAMRs and absolute death counts was conditional on the continuation of historical time-series patterns. These findings support continued surveillance but should not be interpreted as evidence of causality.