Temporal Trends in Mortality Related to Pancreatic Cancer and Cachexia in the United States.

INTRODUCTION: Pancreatic cancer remains one of the most fatal malignancies, and cachexia, a systemic wasting syndrome, is a key determinant of poor outcomes. However, population-level trends in pancreatic cancer mortality where cachexia contributes to death remain understudied. This study analyzes cachexia specifically as a contributing cause of death to capture its systemic role in end-stage disease and its independent contribution to mortality burden. AIM: To evaluate temporal trends and demographic disparities in pancreatic cancer mortality with cachexia as a contributing cause in the United States between 1999 and 2020. METHODOLOGY: A retrospective observational analysis was performed using the CDC Multiple Cause of Death (MCD) database. Adults aged ≥25 years were included if pancreatic cancer (International Classification of Diseases, Tenth Revision (ICD-10): C25) was listed as the underlying cause and cachexia (ICD-10: R64) as a contributing cause. Age-adjusted mortality rates (AAMRs) per million population were computed, and temporal trends were assessed using joinpoint regression with annual percentage change (APC), 95% confidence intervals (CI), and p-values. RESULTS: A total of 4,205 deaths met inclusion criteria. Overall AAMR declined from 1.4 to 0.7 per million, with APCs of -7.35% (95% CI: -9.1 to -5.6; p < 0.001, 1999-2003), -3.30% (95% CI: -4.8 to -1.9; p < 0.01, 2003-2007), and -1.23% (95% CI: -2.2 to -0.3; p = 0.02, 2007-2020). Males (52%) had higher mortality than females (48%), as only two sex categories were analyzed. Most deaths occurred among White individuals (81.6%) and residents of metropolitan regions (81%). Data for Asian/Pacific Islander and American Indian/Alaska Native groups were suppressed due to counts < 10, limiting subgroup analysis. CONCLUSIONS: Mortality from pancreatic cancer with cachexia as a contributing cause has declined over two decades, though sex-, race-, and geography-based disparities persist. Interpretation should consider data suppression for small subgroups and potential misclassification or underreporting of cachexia on death certificates. Continued efforts to improve coding accuracy, nutritional assessment, and palliative care integration are vital to reducing inequities and improving patient outcomes.