Adolescent and young adult cancer death burden in the United States from 1990 to 2023.

e22599 Background: Reports of increasing adolescent and young adult (AYA) cancer burden in the United States (US) may be influenced by detection bias. Thus, we examined AYA cancer mortality over time, a more stable indicator of cancer control progress. Methods: Using Global Burden of Disease 2023 estimates, we examined cancer death counts and rates (per 100000) among US AYAs (ages 15–49) from 1990–2023, overall and by sex. Temporal trends were quantified using estimated annual percentage change (EAPC). Results: In 1990, cancer was the leading cause of death among AYAs with 42599 deaths. By 2023, after declining to 31761 deaths (−25%), cancer ranked third, behind substance use disorders and cardiovascular diseases. Between 1990−2023, 1353140 AYAs died from cancer (53% female), while mortality rates declined from 31.7 to 20.7 (−35%). In 1990, the leading causes of AYA cancer death were lung cancer, breast cancer, colorectal cancer (CRC), leukemia, and brain and central nervous system (CNS) cancer. From 1994-1997, non-Hodgkin lymphoma (NHL) briefly supplanted leukemia among the top five causes. Lung and breast cancer ranked first and second from 1990−2012, until breast surpassed lung cancer in 2013. CRC ranked third from 1990−2014, overtook lung cancer in 2015, and surpassed breast cancer in 2021 to become the leading cause of AYA cancer death. In 2023, leading causes were CRC (4611 deaths), breast cancer (4523), lung cancer (2881), brain and CNS cancer (2642), and leukemia (1940). EAPCs for mortality rates from 1990−2023 for these leading cancers were 0.37 (95% Cl, 0.24, 0.51) for CRC, −2.18 (−2.30, −2.07) for breast cancer, −3.89 (−4.42, −3.36) for lung cancer, −0.78 (−0.90, −0.66) for brain and CNS cancer, and −1.89 (−1.98, −1.81) for leukemia. In males, NHL replaced breast cancer in the top five causes of AYA cancer death from 1990−2009. Pancreatic cancer replaced NHL from 2010−2023, except in 2011. Lung cancer was the leading cause of death from 1990−2013, until colorectal cancer became leading in 2014. Leukemia and brain and CNS tumors remained in the top five from 1990–2023. In females, breast cancer was the leading cause from 1990–2023. Lung cancer ranked second until surpassed by CRC in 2016. Cervical cancer ranked third from 1990−1998, fourth from 1999−2016, and third again from 2017−2023. The fifth ranked cancer shifted from leukemia in 1990 to ovarian cancer from 1991−2012, and to brain and CNS cancer from 2013−2023. Like overall trends, mortality rates declined for all major cancers in both sexes except CRC, for which EAPC increased: 0.43 (0.29, 0.57) in males and 0.30 (0.16, 0.43) in females. Conclusions: In the US, CRC became the leading cause of AYA cancer death in males in 2014 and overall in 2021. Mortality rates have declined in every leading AYA cancer except CRC. Despite overall progress, these findings underscore the need for age-appropriate prevention, early detection, and treatment strategies tailored to the AYA CRC population.