Cohort contributions to trends in the incidence and mortality of intrahepatic cholangiocarcinoma

Background: The incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. We used age-period-cohort (APC) modeling to evaluate the contribution of cohort effects to trends in ICC incidence and mortality in the US. Methods: Incidence data were acquired from the Surveillance, Epidemiology and End-Results (SEER) program. Mortality data were obtained from the Centers for Disease Control and Prevention WONDER Database. APC models using restricted cubic splines were fitted to estimate change in incidence and mortality risk over age, and modification of incidence and mortality risks according to birth cohort and period of diagnosis or death. Likelihood ratio tests were used to summarize improvement in model fit with APC modeling. Results: There were 4,053 cases of ICC at SEER registry sites between 1973-2012. ICC incidence increased with older age and across all birth cohorts examined. Inclusion of cohort effects tended to improve model fit relative to an age-period model (likelihood ratio test P=0.082). The national crude ICC-related mortality rate increased from 2.9 to 5.0 per 100,000 among males and 2.7 to 4.6 per 100,000 among females. Among males, ICC mortality risk varied across birth cohorts, and inclusion of cohort effects in a model predicting ICC mortality risk improved model fit (likelihood ratio test P=0.001), but cohort effects did not alter model fit among females (P=0.223). Conclusions: ICC incidence and mortality have increased over time in the United States. Birth cohort effects influenced increased ICC incidence and ICC mortality among males, but were not evident in the trend of ICC mortality among females.