Trends of mortality among patients with malignant neoplasms of digestive system in the United States from 2007 to 2021.

Background: While malignant neoplasms (MNs) of digestive system (MNDS) remain a leading cause of cancer mortality, evolving patterns of cause-specific deaths in the modern treatment era are poorly characterized. This study aimed to depict the trends in cause-specific mortality among MNDS patients in the U.S. from 2007 to 2021, stratified by clinical and demographic factors, with particular focus on the growing impact of non-neoplasm causes of death (CODs). Methods: This retrospective study analyzed incidence-based mortality rates from 22 registries of the Surveillance, Epidemiology, and End Results program. Patients diagnosed with MNDS in 2000-2021 who died in 2007-2021 were included. Mortality rates were age-adjusted to the 2000 U.S. standard population. Trends of mortality rates were quantified by annual percent changes (APCs), calculated with Joinpoint regression. We stratified the cohort by tumor site, age at death, sex, race, and tumor stage. In each subgroup, mortality rates were classified by COD into MNDS, non-digestive system MNs, non-MNs, non-neoplasm diseases, and unknown COD. In the overall cohort, non-neoplasm CODs were further subclassified. Results: From 2007 to 2021, 1,318,354 deaths occurred among MNDS patients, corresponding to an average mortality rate of 619.27 [95% confidence interval (CI): 618.2, 620.34] per 1,000,000 person-years. The overall mortality increased by 0.53% per year (95% CI: 0.40-0.67%; P<0.001), driven by the increasing non-neoplasm mortality of 3.15% per year (95% CI: 2.59-3.78%; P<0.001) despite declining MNDS-specific mortality (APC: -0.51%; 95% CI: -0.65% to -0.36%; P<0.001). Both sexes demonstrated similar mortality patterns. Colorectal MNs demonstrated a decline in MNDS-specific mortality (APC: -1.46%; 95% CI: -1.58 to -1.34%; P<0.001), but increasing non-neoplasm mortality (APC: 2.72%; 95% CI: 2.15-3.39%; P<0.001) led to overall mortality increase (APC: 0.25%; 95% CI: 0.05-0.47%; P=0.01). Meanwhile, patients with pancreatic, biliary, and anal MNs experienced mortality increases from both MNDS-specific and non-neoplasm CODs. Notably, medical complications displayed the fastest acceleration (APC, 8.58%; 95% CI: 4.97-14.17%; P<0.001) among non-neoplasm CODs. American Indian or Alaska Native was the only race with non-decreasing MNDS-specific mortality (APC: 0.63%; 95% CI: -0.56% to 1.95%; P=0.22) alongside the fastest-growing non-neoplasm mortality (APC: 4.23%; 95% CI: 3.21-5.52%; P<0.001). Localized-stage patients had the most rapid non-neoplasm mortality increase (APC: 6.42%; 95% CI: 5.60-7.43%; P<0.001) across tumor stages. Conclusions: Non-neoplasm diseases have become the dominant determinant of mortality increases in MNDS patients. This paradigm change requires transforming MNDS care to address comorbidities alongside cancer treatment, particularly for high-risk subgroups.