Trends in mortality from cancer and sepsis in the United States, 1999 to 2023: An analysis of CDC WONDER data

Cancer remains the second leading cause of death in the United States (U.S.), with increasing incidence among younger adults. Sepsis, a life-threatening organ dysfunction caused by infection, frequently complicates cancer due to disease-related and treatment-induced immunosuppression. Understanding cancer-sepsis mortality trends is essential for identifying high-risk populations and improving prevention and clinical management strategies. We analyzed U.S. mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death database to identify deaths among adults aged ≥ 25 years in which both cancer (International Classification of Diseases, Tenth Revision C00-D48) and sepsis (International Classification of Diseases, Tenth Revision A41) were listed on the same death certificate, representing concomitant cancer-sepsis mortality. Age-adjusted mortality rates per 100,000 population were calculated and temporal trends were assessed using Joinpoint regression. Statistical significance was set at P < .05. From 1999 to 2023, a total of 20,108,555 U.S. adults aged 25+ died from cancer complicated by sepsis. From 1999 to 2023, the average annual percentage change (AAPC) decreased by 1.09% (95% confidence interval, -1.33--0.84%). Rates fell from 417.6 per 100,000 in 1999 to 322.0 in 2023, showing a steady decline until 2018 (annual percent change [APC]: -1.32%), a brief rise from 2018 to 2021 (APC: 2.17%), and a significant drop from 2021 to 2023 (APC: -3.65%). Mortality was highest in men (AAPC: -1.33%) and Black or African American individuals (AAPC: -1.68%), as well as in nonmetropolitan areas (AAPC: -0.60%) and the Southern U.S. (AAPC: -1.02%). Most age groups experienced significant declines, particularly middle-aged adults, while the youngest (25-34) and oldest (85+) age groups showed minimal long-term change. All racial and ethnic groups showed improvement, although American Indian or Alaska Native trends remained largely flat until a notable decline (APC: -8.26% from 2021 to 2023). Most deaths occurred in hospitals (38%) or at home (35%), with fewer in nursing homes, hospices, or other settings. Concomitant cancer-sepsis mortality declined overall in the U.S. from 1999 to 2023, but substantial disparities persist by sex, race/ethnicity, geography, and urbanization, reflecting inequities in access to oncology care, critical care, and timely sepsis management.