The incidence of cholangiocarcinoma (CCA) in the United States increased from 2001 to 2017, according to data published in The Oncologist

This increase coincided with a decrease in the incidence of cancer of unknown primary (CUP). Though these data suggest that cases of CUP began to be reclassified as CCA, the decrease in CUP incidence does not fully account for the increase in CCA incidence, according to researchers. 

“The results show this to be a true increase [in CCA incidence] not wholly attributable to reclassification from cancer of unknown primary and indicate a need for improved CCA surveillance and management, particularly for advanced disease,” the researchers wrote.

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The researchers noted that an increase in CCA incidence up to 2015 had been reported previously. The aim of the current study was to determine if this trend continued through 2017.

The study included data from 40,030 patients with CCA and 32,980 patients with CUP, derived from the Surveillance, Epidemiology, and End Results 18 registry. The incidence rates were reported per 100,000 person-years and were age-adjusted according to the population estimates by the US Census Bureau for the year 2000.

The overall age-adjusted incidence of CCA from 2001 to 2017 was 3.65 per 100,000 person-years — 1.19 for intrahepatic CCA (iCCA) and 2.46 for extrahepatic CCA (eCCA). 

The incidence of CCA increased by 43.8% over the period studied, from 3.08 in 2001 to 4.43 in 2017. The incidence of iCCA increased by 148.8%, and the incidence of eCCA increased by 7.5%. 

The incidence of CUP decreased by 54.4% over the same time period, from 4.65 in 2001 to 2.12 in 2017. 

“The incremental difference between age-adjusted iCCA and CUP incidences increased monotonically from −3.85 in 2001 to −0.13 in 2017,” the researchers wrote.

They noted that iCCA can be misclassified as CUP because of similarities in presentation and histopathology. However, it hasn’t been clear if the misclassification of iCCA as CUP occurs often enough to have a substantial impact on the reported incidence of iCCA. 

“The observed divergent and opposing trends in CUP vs iCCA incidence from 2001-2017, along with the observed monotonic increase in the incremental difference between iCCA and CUP incidences across the study period, provide evidence for a true increase in iCCA incidence that may not be wholly explained by a decreased misclassification of iCCA as CUP.”

The median overall survival from diagnosis was 8 months for CCA, 6 months for iCCA, 9 months for eCCA, and 2 months for CUP.

For CCA, the annual mortality rate declined from 45.2% in 2001 to 38.7% in 2016. For iCCA, it declined from 57.1% to 41.2%. The annual mortality rate generally remained stable for eCCA — 40.9% in 2001 and 37.0% in 2016 — and for CUP — 64.3% in 2001 and 68.6% in 2016.

Disclosures: This study was supported by Incyte Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Javle M, Lee S, Azad NS, et al. Temporal changes in cholangiocarcinoma incidence andmortality in the United States from 2001 to 2017. Oncologist. Published online August 16, 2022. doi:10.1093/oncolo/oyac150