Early-onset pancreatic cancer in the United States (1991–2021): Temporal trends, geographic variation, and gender disparities.

e16444 Background: Early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed before the age of 50, remains a growing public health concern. This study examines national trends in EOPC incidence and mortality, highlighting disparities by state and gender. Methods: Using the Global Burden of Disease (GBD) Study 2021 Results Tool, Age-standardized mortality rates (ASMR) and age-standardized incidence rates (ASIR) for patients aged 15–49 years were extracted and data were stratified by year, sex, and location. Mortality and incidence trends were analyzed using Joinpoint regression, and annual percentage change (APC) was calculated Results: The Joinpoint regression analysis of EOPC mortality in the U.S. (1991–2021) shows an ASR increase from 1991 to 2002 (APC: +2.13%), stabilization from 2002 to 2007 (APC: -0.13%), and a significant decline starting in 2007, with ASR decreasing at -2.85% per year until 2013. This downward trend continued from 2013 to 2017 (APC: -2.02%) and slowed from 2017 to 2021 (APC: -1.80%) The Joinpoint regression analysis of EOPC in the U.S. (1991–2021) shows an ASIR increase from 1991 to 2002 (APC: +2.57%), stabilization from 2002 to 2008 (APC: -0.23%), a sharp decline from 2008 to 2012 (APC: -3.11%), and a slower decline from 2012 to 2021 (APC: -0.93%). In 2021, the highest EOPC mortality rates were observed in Mississippi (1.73 per 100,000), West Virginia (1.65), and New Mexico (1.49), while the lowest were in Utah (0.70), Massachusetts (0.73), and Rhode Island (0.78). ASIR followed a similar trend, with Mississippi (2.22), West Virginia (2.16), and New Mexico (1.99) reporting the highest case rates, while Utah (1.01), Massachusetts (1.04), and California (1.07) had the lowest. APC analysis showed that EOPC mortality increased most in West Virginia (2.56), whereas the steepest declines were seen in the District of Columbia (-1.65). Similarly, incidence rates increased most in Mississippi (4.06), while Utah (0.02) exhibited the lowest growth. Sex-specific trends revealed a decrease in EOPC mortality for males by 8.12% (from 1.29 per 100,000 in 1991 to 1.18 in 2021), while female mortality increased by 3.71% (from 0.77 to 0.79). Incidence rates declined slightly in males by 1.96% (from 1.62 to 1.58), but increased by 11.50% in females (from 1.00 to 1.11). Conclusions: From 1991 to 2021, early-onset pancreatic cancer incidence and mortality in the United States increased initially, stabilized, and then declined beginning in the late 2000s. Despite overall improvement, substantial geographic and sex-based disparities persist. Mortality and incidence have declined in males but increased in females, highlighting the need for targeted prevention and early detection strategies in high-burden regions and at-risk populations.