Early-onset gastrointestinal cancers: Rural-urban divide and cancer-site disparities in outcomes.

e23203 Background: Early-onset gastrointestinal (eoGI) cancers, defined as diagnoses occurring before age 50, represent a growing public health concern in the United States (US). While incidence rates of several eoGI malignancies (most notably colorectal cancer) have risen over recent decades, population-level mortality trends remain less clearly characterized. We therefore examined national trends in age-adjusted mortality from eoGI cancers in the US, with a focus on cancer site-specific, geographic, and urban–rural differences. Methods: We retrieved the mortality data from the CDC WONDER underlying causes of death database (years: 1999–2020) for the population aged 18-49 with “Neoplasms of digestive organs” (ICD-10 C15-26) listed as “underlying cause of death”. We analyzed age-adjusted mortality rates (AAMRs) per 100,000 population and assessed temporal trends in the average annual percent change (AAPC) of AAMRs. AAPC and 95% CIs were estimated using the NCI Joinpoint regression program 5.4.0. with the log-scale AAMRs as the dependent variable and year as a continuous covariate, and a p-value < 0.05 considered statistically significant. Subgroup analyses were performed by cancer site, U.S. Census geographic division, and level of urbanization based on the National Center for Health Statistics 2013 Classification. Results: A total of 180,512 eoGI cancer–related deaths were identified. Overall, AAMRs declined, with an AAPC of −0.25% (95% CI, −0.34 to −0.16; p < 0.05). However, trends varied substantially by cancer site. Early-onset colorectal cancer demonstrated a significant increase in mortality (AAPC, 0.56%; 95% CI, 0.30–0.91; p < 0.001). Urban–rural analyses revealed rising mortality for eoGI cancers in rural areas (AAPC, 0.30%; 95% CI, 0.04–0.57; p = 0.01), stable trends in small and medium metropolitan areas (AAPC, 0.06%; 95% CI, −0.16 to 0.24; p = 0.24), and a significant decline in large metropolitan areas (AAPC, −0.46%; 95% CI, −0.84 to −0.08; p = 0.02). By U.S. Census geographic division, mortality declined in the Middle Atlantic (AAPC, −0.57%; p < 0.01) and South Atlantic (AAPC, −0.54%; p < 0.01), whereas mortality increased in the West North Central division (AAPC, 0.34%; p = 0.03). Conclusions: Despite an overall decline in age-adjusted mortality from eoGI cancers in the US, this improvement was not uniform across cancer sites or regions. Early-onset colorectal cancer continues to demonstrate a consistent rise in mortality, particularly in rural areas and select geographic divisions, highlighting persistent and emerging disparities. These findings underscore the need for targeted public health strategies that aim to improve and ensure equitable access to screening and high-quality cancer care. Population Group(1999-2020) AAPC (%) 95% CI (Lower) 95% CI (Upper) P-value Large metropolitan −0.46 −0.84 −0.08 0.01 Small/medium metropolitan 0.06 −0.12 0.25 0.45 Rural 0.31 0.04 0.58 0.026