Mortality Trends of Biliary Tract Cancers in the United States, 1999-2023: a CDC-WONDER Analysis

Biliary tract cancers (BTCs) comprise a heterogeneous group of malignancies, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, ampulla of Vater tumors, and other or unspecified BTCs. We examined population-level BTC mortality trends and disparities in the US from 1999 to 2023.

Deaths among adults aged ≥ 35 years were obtained from CDC WONDER using ICD-10 codes C22.1, C23, C24.0, C24.1, C24.8, and C24.9. AAMRs per 100,000 were calculated and assessed using Joinpoint regression, with stratification by sex, race/ethnicity, age, census region, and urbanization level. Urbanization analyses used standardized data through 2020.

From 1999 to 2023, 226,056 BTC deaths were recorded. Annual deaths increased from 6,121 to 13,637, and the AAMR increased from 4.37 to 6.10 per 100,000 (AAPC, 2.22%; 95% CI, 1.95%-2.50%; P < 0.001), with acceleration after 2007. The Non-Hispanic Black population exhibited the fastest increase in mortality among racial/ethnic groups, with an AAPC of 3.20%, whereas Hispanics had the highest AAMR in 2023. The 35-44-year age group showed the fastest increase despite low mortality (AAPC, 3.77%). In 2023, the Midwest had the highest AAMR, at 5.50 per 100,000, followed by the West at 5.32 per 100,000. In standardized urbanization-stratified data through 2020, metropolitan areas had a higher AAMR than nonmetropolitan areas (4.65 vs. 4.30 per 100,000). Subtype-specific analyses showed that intrahepatic cholangiocarcinoma accounted for the largest proportion of deaths (132,830; 58.76%) and had an increasing AAMR from 1.82 to 4.17 per 100,000, whereas gallbladder cancer accounted for 51,720 deaths (22.88%) and had a declining AAMR from 1.46 to 0.98 per 100,000. Extrahepatic bile duct cancer, ampulla of Vater cancer, and other/unspecified BTCs contributed 18,669, 5,135, and 17,702 deaths, respectively, highlighting that pooled BTC estimates may mask divergent subtype patterns. These opposite iCCA and GBC patterns supported separate subtype reporting rather than interpretation of the pooled BTC estimate alone in this study.

BTC mortality among US adults aged ≥ 35 years increased from 1999 to 2023, with demographic, geographic, urbanization-related, and subtype-specific heterogeneity. These findings support subtype-aware surveillance, early detection, and equitable resource allocation.