Premature cancer mortality in the United States, 1999–2023: Analysis of CDC WONDER data.

11042 Background: Premature cancer deaths (defined as mortality in adults aged 20-69 years) represent significant years of potential life lost (YPLL) and substantial disease burden, yet comprehensive national trends remain insufficiently characterized. Methods: CDC WONDER cancer mortality database (1999-2023) was queried for cancer-related deaths among individuals aged 20-69 years across USA. Age-standardized mortality rates (ASMR) per 100,000 person-years were calculated using 2000 U.S. Census standard population. Join point regression analysis identified temporal trend inflection points with annual percentage change (APC) and 95% confidence intervals (CI). Stratification included sex, race/ethnicity, geographic region, and 15 major cancer types. Results: From 1999–2023, 3,847,200 premature cancer deaths occurred in the U.S. (mean 153,888/year). Annual deaths increased 12.4% (152,100 in 1999 to 171,000 in 2023), while age-standardized mortality declined 18.6% (ASMR 87.3 to 71.1 per 100,000). Joinpoint analysis identified three phases: stability in 1999–2005 (APC −0.42%), accelerated decline in 2005–2015 (APC −2.18%), and slower improvement in 2015–2023 (APC −0.73%). Males had higher mortality than females in 1999 (ASMR 105.4 vs 69.2), with declines in both sexes (APC −1.89% males; −2.34% females), narrowing the male–female gap from 52.2% to 37.8% by 2023. Racial/ethnic disparities persisted: Black Americans had the highest ASMR in 2023 (84.3), 18.6% higher than Whites (71.1), with slower declines (APC −1.23% vs −2.07%); Hispanics/Latinos had the lowest ASMR (52.8) and fastest declines (APC −3.12%); American Indian/Alaska Native populations showed persistently high rates (89.2) with minimal change (APC −0.18%). In 2023, leading contributors were lung (38,200 deaths; ASMR 17.5; APC −3.78%), breast (23,100; 10.5; −2.45%), colorectal (11,800; 5.3; −3.12%), pancreatic (8,400; 3.8; −0.28%), and ovarian cancer (6,200; 2.8; −1.86%), together accounting for 58.2% of premature deaths. Cervical cancer declined sharply (APC −4.23%), while melanoma increased (APC +2.15%). Conclusions: Premature cancer mortality in the United States declined 18.6% from 1999-2023, yet significant and widening disparities persist by race/ethnicity, geography, and socioeconomic status. Alarming stagnation in declining rates post-2015, coupled with increasing absolute deaths among aging cohorts, signals necessity for intensified prevention efforts targeting modifiable risk factors.