Divergent Biliary Tract Cancer Trajectories

Cholangiocarcinoma (CCA) and gallbladder cancer demonstrate profoundly divergent epidemiological trajectories across 2 decades (2003 to 2017), demanding urgent investigation. Population-based registry data from the cancer incidence in 5 continents project, spanning 3 periods (2003 to 2007, 2008 to 2012, and 2013 to 2017) across 12 Asian countries, reveal an exponential acceleration in CCA, with striking gender-specific patterns indicating distinct aetiological mechanisms. Between 2003 and 2017, CCA incidence increased 136.3% while gallbladder cancer rose only 7.7%, which is a 128.6 percentage-point differential. Geographic variation was extreme: Iran and Kuwait demonstrated significant CCA escalation; Israel showed a 234.7% CCA increase, whereas gallbladder cancer declined by 35.6%. In contrast, Japan, Korea, and China exhibited substantial CCA growth (126.8% to 144.0%), whereas gallbladder cancer remained stable. Endemic liver-fluke regions showed attenuated divergence (Thailand: 60.1% CCA vs. 26.6% gallbladder, 33.5 percentage-point gap). ARIMA modelling reveals alarming 2030 projections: Republic of Korea, 3.38 per 100,000 (95% CI: 0.39-6.36; 193% increase); Japan, 2.19; China, 1.09; Thailand, 2.02. Gallbladder cancer projects relative stability. Gender-stratified analysis reveals striking divergence: CCA demonstrates pronounced male predominance in nonendemic regions (Japan: 1.62; Korea: 1.68; China: 1.43 male-to-female ratios), suggesting male-predominant behavioural and metabolic risk factors, including smoking, alcohol consumption, and metabolic dysfunction-associated fatty liver disease (MAFLD). Conversely, gallbladder cancer demonstrates universal female predominance (0.38 to 0.75 ratios) reflecting cholelithiasis epidemiology. This profound gender divergence provides compelling evidence for independent aetiological mechanisms. These findings mandate urgent investigation of emerging nonparasitic CCA risk factors in developed Asian economies, prospective studies examining smoking, alcohol, MAFLD, and metabolic syndrome, and enhanced surveillance infrastructure.