Mortality trends of gallbladder cancer in middle-aged and older adults in the United States: a CDC WONDER analysis from 1999 to 2023.

Background: Gallbladder cancer (GBC) is a rare but highly lethal malignancy, often diagnosed at advanced stages due to the absence of early symptoms. Although its incidence is relatively low in the United States, marked demographic and geographic disparities persist, and long-term national mortality trends remain insufficiently characterized. Methods: We analyzed gallbladder cancer·-related deaths (ICD-10 code C23) among U.S. adults aged 45 years and older from 1999 to 2023 using the CDC WONDER database. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated. For age-stratified analyses, crude mortality rates were used instead of AAMRs, as age adjustment within predefined strata is inappropriate. Temporal trends were assessed using joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC) overall and by sex, age group, race and ethnicity, census region, and urbanization level. Results: During the study period, 50,938 gallbladder cancer-related deaths were recorded. Overall, the AAMR declined from 2.10 per 100,000 in 1999 to 1.39 per 100,000 in 2023, with significant decreases across multiple time intervals (AAPC = -1.76, 95% CI: -2.16 to -1.36, P ≤ 0.05). Mortality increased markedly with age, and individuals aged 85 years and older consistently exhibited the highest rates. Females had higher mortality rates than males throughout the study period (1.72 vs. 1.01 per 100,000 in 2023), although declining trends were observed in both sexes. Significant reductions in mortality were observed among Hispanic, non-Hispanic White, and non-Hispanic Other populations; however, no significant decline was observed among non-Hispanic Black individuals (AAPC = -0.14, 95% CI: -0.60 to 0.33, P > 0.05). Regionally, mortality was highest in the Northeast and lowest in the South. Mortality rates were consistently higher in metropolitan than in non-metropolitan areas (1.51 vs. 1.48 per 100,000 in 2020). Conclusion: Although gallbladder cancer mortality among middle-aged and older adults in the United States has declined over the past two decades, this improvement has been uneven. Persistent disparities by age, sex, race and ethnicity, region, and urbanization remain, particularly among non-Hispanic Black populations. These findings underscore the need for targeted and equitable public health strategies to further reduce gallbladder cancer mortality.