Mortality trends in digestive system malignancies among US adults aged 45 years or older, 1999 to 2023

Digestive system malignancies remain a major cause of cancer mortality in the United States (US). Updated evidence through 2023 is needed to characterize recent trends, disparities, and cancer-site heterogeneity among adults aged 45 years or older. We conducted an ecological time-trend secondary analysis of publicly available, deidentified, aggregate mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Underlying Cause of Death database. US residents aged ≥ 45 years who died from digestive system malignancies (International Classification of Diseases, 10th Revision [ICD-10] C15-C26) during 1999 to 2023 were included. Age-adjusted mortality rates (AAMRs) per 1,00,000 were directly standardized to the 2000 US standard population, whereas age-group analyses used crude rates. Joinpoint regression estimated annual percent changes (APCs) and average annual percent changes (AAPCs), with Benjamini-Hochberg (BH) adjustment for multiple comparisons. Between 1999 and 2023, the number of deaths increased from 1,25,353 to 1,66,045, whereas the national AAMR declined from 131.59 to 108.28 per 1,00,000 population (AAPC = -0.89%; 95% confidence interval: -0.98 to -0.79; q < 0.001). The annual decline was smaller after 2008. Men consistently had higher AAMRs than women, and non-Hispanic Black adults had the highest mortality rate but the most rapid long-term decline (AAPC = -1.55%; q < 0.001). Recent numerical changes among women, non-Hispanic White adults, and adults aged 45 to 54 years were not statistically significant after BH adjustment. In 2023, state-level AAMRs ranged from 92.31 in Colorado to 133.42 per 1,00,000 in Mississippi. Under the consistent 2013 National Center for Health Statistics (NCHS) classification, the 2020 AAMR was higher in nonmetropolitan than metropolitan areas (117.23 vs 105.67 per 1,00,000). Cancer-site-specific patterns were heterogeneous: the largest absolute reductions in AAMRs occurred for colorectal and stomach cancers, whereas AAMRs increased for liver and intrahepatic bile duct, pancreatic, anal and anal canal, and small-intestinal cancers. Despite a modest long-term decline in age-adjusted mortality from digestive system malignancies, the absolute number of deaths increased, and substantial demographic, geographic, and cancer-site-specific heterogeneity persisted. Continued site-specific and equity-focused surveillance is needed to guide prevention, early detection, and resource allocation.