Cholangiocarcinoma: State-of-the-art knowledge and challenges

Cholangiocarcinoma (CCA) is a group of malignant tumours that originates from the biliary tree. Depending on the anatomical location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA). The use of the term extrahepatic, instead, will be soon elim - inated from every classification. Besides the anatomical location, CCAs are heterogeneous also in terms of aetiological, histopatho - logical and molecular features. Regardless of the type of CCA, these tumours are universally characterized by clinical aggressiveness and limited treatment options. Due to limited symptoms in the initial/ pre‐invasive stages of the disease ( silent disease), CCA is most often diagnosed at the advanced stage (inoperable or metastatic), when potentially curative treatments such as surgical resection cannot be applied. Furthermore, after surgery, high recurrence rate (up to 50% within first 12 months) applies for early stage patients as well. In ad - dition, the efficacy of systemic treatments is very limited and, thus, novel agents are highly needed for this fatal disease. This body of clinical evidence, together with the epidemiological observation of an increasing trend of incidence and mortality, indicates CCA as a major health concern worldwide