Cause-specific mortality in a population-level cohort of pancreatic cancer patients following chemotherapy: A SEER-based study

Pancreatic adenocarcinoma remains highly lethal. How modern chemotherapy reshapes the full mortality profile, including competing non‑cancer deaths, is incompletely defined. Using Surveillance, Epidemiology, and End Results (2010-2021), we identified 9624 adults (20-89 years) with primary pancreatic adenocarcinoma who received systemic chemotherapy. Cause of death (International Classification of Diseases, Tenth Revision) was classified as pancreatic cancer, other cancers, or non‑cancer causes. Stage-stratified analyses characterized mortality heterogeneity. Standardized mortality ratios (SMRs) versus the general US population were calculated in SEER*Stat; multivariable Poisson regression assessed risk factors. Temporal patterns were examined across ≤1 year, 1 to 5 years, and >5 years from diagnosis. Over a median follow-up of 14.2 months, 8218 deaths occurred. Pancreatic cancer accounted for 90.6% (n = 7448); non‑cancer causes accounted for 6.1% (n = 498), and other cancers accounted for 3.3% (n = 272). Non-cancer mortality comprised 7.8% of stage I/II deaths versus 5.1% in stage III/IV, reflecting longer survival enabling competing risks. Overall, non‑cancer mortality was markedly elevated (SMR 15.38, 95% confidence interval: 14.06-16.79), peaking in year 1 (SMR 96.10) and declining thereafter (1-5 years, SMR 13.63; >5 years, SMR 3.19). Cardiovascular deaths carried the greatest non‑cancer burden (heart disease SMR 9.96; cerebrovascular disease SMR 12.7). Infectious causes showed the highest relative risks (septicemia SMR 20.3; pneumonia/influenza SMR 88.69), concentrated in the first year. Chronic obstructive pulmonary disease (SMR 17.57) and diabetes (SMR 19.3) were additional contributors. Older patients (70-89 years) experienced the steepest early mortality. Suicide risk was strikingly increased (SMR 113.68), underscoring substantial psychological distress. In chemotherapy‑treated pancreatic cancer, non‑cancer mortality is substantial, time‑dependent, and dominated by cardiovascular and infectious causes in the first year after diagnosis. These data support integrated cardio‑oncology pathways, aggressive infection prevention, metabolic and pulmonary co‑management, and early psychosocial interventions to reduce preventable deaths and improve outcomes.