Genetic Classification of iCCA Can Have Significant Prognostic Value

The clinical heterogeneity of intrahepatic cholangiocarcinoma (iCCA) may be a result of multiple cells of origin and variable driver gene alterations; however, certain features are shared with hepatocellular carcinoma (HCC) and extrahepatic CCA (eCCA). A statistical algorithm, the hidden-genome classifier, classifies tumors by identifying tumor genetic origin and integrating multilevel metagenetic information. Dr Yi Song presented results from a retrospective review using the hidden-genome classifier to quantify the genetic heterogeneity of iCCA with a view toward improved tumor classification. Investigators trained and internally validated the hidden-genome classifier using eCCA, gallbladder cancer (GBC), and HCC as extremes on the spectrum.

A retrospective review of patients with biopsy-confirmed iCCA, eCCA, GBC, and HCC was conducted, and a total of 1264 patients were analyzed, 527 with iCCA, 206 with eCCA, 233 with GBC, and 298 with HCC. The iCCA tumors demonstrated a continuous spectrum of alterations similar to eCCA and HCC, ranging from biliary class (122 tumors) to intermediate class (375 tumors) to HCC class (30 tumors).

In patients with unresected iCCA, the median survival ranged from 1 year in the biliary class to 1.8 years in the intermediate class to 2.3 years in the HCC class. In patients who underwent resection, the median survival was 2.4 years in the biliary class, which was lower than both the intermediate class (5.1 years) and the HCC class (4.9 years; Table).

Overall, iCCAs are heterogeneous tumors with a spectrum of genetic alterations with some similarities to HCC and eCCA. Classification of genetic heterogeneity in iCCA may have significant prognostic value.

Source: Song Y, Boerner T, Drill E, et al. Genetic heterogeneity of intrahepatic cholangiocarcinoma: implication for outcome. Poster presented at: ASCO Gastrointestinal Cancers Symposium, January 19-21, 2023; San Francisco, CA. Abstract 595.