Distant Metastases in Patients with Intrahepatic Cholangiocarcinoma: Does Location Matter? A Retrospective Analysis of 370 Patients.

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive tumor entity, and distant metastases are common. However, studies investigating patterns and clinical relevance of distant metastases are rare. Therefore, we aimed to analyze occurrence, location, and prognostic impact of distant metastases on overall survival (OS).

Methods: Between 1997 and 2018, 417 patients with ICC were treated at our tertiary care center. Distant metastases and intrahepatic tumor burden were retrospectively evaluated in a longitudinal approach using volumetric assessment of cross-sectional imaging studies and all available medical/histopathological reports.

Results: Finally, 370 patients with histopathologically confirmed ICC were included. Of these, 186 showed distant metastases, either initially ( n  = 59) or during follow-up ( n  = 127). The most common metastatic sites were the lung ( n  = 105), peritoneum ( n  = 81), and bone ( n  = 50). After detection of lung metastases, the residual median OS was 5.3 months; followed by peritoneal metastases, 4.5 months, and bone metastases, 4.4 months ( P =0.17). At the time of first metastatic occurrence, residual OS according to intrahepatic tumor burden of <25%, 25-50%, and >50% was 6.5 months, 4.9 months, and 1.2 months, respectively ( P < 0.001). In multivariate hazard regression, hepatic tumor burden, liver function, and subsequent treatment were significant predictors of survival.

Conclusions: During the disease course, every second patient developed extrahepatic metastases. While the presence of distant metastases was associated with poor patient outcomes, there was no significant difference between metastatic sites. However, hepatic tumor burden was the life-limiting risk factor in a majority of patients at the time of distant metastatic disease.