Molecular Profiling and Treatment Pattern Differences between Intrahepatic and Extrahepatic Cholangiocarcinoma.

BACKGROUND: Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies.

METHODS: This multi-center collaboration included patients with ICC or ECC treated at one of eight participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were two-sided.

RESULTS: Among 1,039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early-stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%), (all p < 0.00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%), (all p < 0.001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months, p < 0.001).

CONCLUSIONS: Patients with advanced ECC have low rates of molecular profiling, possibly in part due to insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.