International trends in biliary tract cancer-related mortality, 2000-2022: An observational study of the World Health Organization Mortality Database

Background and Aims: Biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer, exhibit poor prognosis. This study examined temporal trends in mortality due to BTCs and their major subtypes at international, regional, and national levels. Approach and Results: This observational study used the World Health Organization mortality database. Locally weighted regression (LOESS) was used to produce a smoothed curve of long-term international and regional BTC and major subtype-related mortality rates in 2000-2022 based on available data from countries. Trends in age-standardized mortality rates (ASRs) during 2013-2022 for individual countries were examined using joinpoint regression analysis. Internationally, LOESS-smoothed ASRs per 100,000 population due to BTCs were 2.8 (95% CI: 2.5-3.1) in 2000, and 2.7 (2.3-3.1) in 2022. LOESS-smoothed BTC-related ASRs were the highest in the Western Pacific region at 4.2 (1.8-6.6) in 2022, compared with those in the European and American regions at 2.6 (2.3-2.9) and 2.2 (1.8-2.6), respectively. Among major subtypes, LOESS-smoothed ASRs due to iCCA increased by 120.0%, those due to gallbladder cancer decreased by 45.5%, and those due to extrahepatic cholangiocarcinoma remained stable between 2000 and 2022. Disparities in BTC and major subtype-related ASR trends were observed between countries during 2013-2022, with iCCA-associated ASRs showing increasing trends in many countries. Conclusions: Although internationally estimated BTC-associated ASRs showed a stable trend over the last 2 decades, a large increase in estimated iCCA-associated ASRs necessitates developing effective screening for high-risk individuals and disease management strategies.