National trends and disparities in early-onset non-colorectal cancer mortality in the United States, 1999–2023: A population-based analysis of 240,190 deaths.

12106 Background: Early-onset non-colorectal malignancies account for a substantial share of premature cancer mortality in the United States, yet comprehensive national evaluations of long-term trends and disparities remain limited. Methods: We analyzed CDC WONDER Multiple Cause-of-Death data from 1999–2023, identifying deaths among individuals aged 15–54 years with non-colorectal malignancies. Age-adjusted mortality rates (AAMRs) per 1 million population were standardized to the 2000 U.S. standard population. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Results: A total of 240,190 deaths from early-onset non-colorectal malignancies occurred during the study period. Overall AAMRs declined from 61.45 (95% CI 60.22–62.68) in 1999 to 52.76 (95% CI 51.67–53.87) in 2023. Largest proportion of deaths occurred at home (43.4%), followed by inpatient or medical facilities (39.6%). Among women, AAMRs increased steadily from 36.01 (95% CI 35.02–37.04) in 1999 to 39.03 (95% CI 38.03–40.05) in 2023 (AAPC +0.33%, 95% CI 0.20–0.47). In contrast, men exhibited substantially higher but declining mortality, with an accelerated decline after 2012 (APC −2.25%, 95% CI −2.67 to −2.02). Racial and ethnic disparities persisted. Non-Hispanic Black populations showed significant reductions (AAPC −2.25%), Non-Hispanic Asian/Pacific Islander populations experienced the steepest declines (AAPC −2.22%), while Non-Hispanic American Indian/Alaska Native populations exhibited an early surge (APC +9.57%) followed by prolonged plateauing with persistently high rates. Metropolitan areas experienced faster declines (AAPC −0.72%) than non-metropolitan areas. Conclusions: The post-2012 acceleration in mortality reduction suggests progress in cancer management; however, these gains were uneven and masked substantial disparities. Men experienced marked declines but continued to have significantly higher mortality than women, while the steady increase in female mortality raises concern for unaddressed sex-specific risk and disease dynamics. Stagnant trends among individuals aged 15–34 years indicate limited benefit of advances in oncology for the youngest patients. Racial, ethnic, and geographic inequities remained pronounced, with persistently elevated mortality among Non-Hispanic Black and American Indian/Alaska Native populations, slower improvements in non-metropolitan areas, and consistently high rates in several Southern and Appalachian states. Together, these findings indicate that national progress has not translated into equitable outcomes and highlight the urgent need for targeted prevention, earlier diagnosis, and region- and population-specific cancer control strategies to reduce avoidable early-life cancer mortality.