Clinical treatment of cholangiocarcinoma: an updated comprehensive review

Cholangiocarcinoma (CCA) is a heterogeneous group of neoplasms of the bile ducts and represents the sec-ond most common hepatic cancer after hepatocellular carcinoma; it is sub-classified as intrahepatic cholan-giocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA), the latter comprising both perihilar cholangiocarcinoma (pCCA or Klatskin tumor), and distal cholangiocarcinoma (dCCA).The global incidence of CCA has increased worldwide in recent decades. Chronic inflammation of biliary epi-thelium and bile stasis represent the main risk factors shared by all CCA sub-types. When feasible, liver resection is the treatment of choice for CCA, followed by systemic chemotherapy with capecitabine. Liver transplants represent a treatment option in patients with very early iCCA, in referral cen-ters only. CCA diagnosis is often performed at an advanced stage when CCA is unresectable. In this setting, systemic chemotherapy with gemcitabine and cisplatin represents the first treatment option, but the prog-nosis remains poor.In order to ameliorate patients' survival, new drugs have been studied in the last few years. Target therapies are directed against different molecules, which are altered in CCA cells. These therapies have been studied as second-line therapy, alone or in combination with chemotherapy. In the same setting, the immune check-points inhibitors targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T -lymphocyte antigen-4 (CTLA-4), have been proposed, as well as cancer vaccines and adoptive cell therapy (ACT). These experimental treatments showed promising results and have been proposed as second-or third-line treatment, alone or in combination with chemotherapy or target therapies.(c) 2022 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

Cholangiocarcinoma is a heterogeneous group of neoplasms of the bile ducts, with an increasing global incidence. Chronic inflammation of the biliary epithelium and bile stasis are the main risk factors. Liver resection followed by chemotherapy is the preferred treatment option, and targeted therapies and immune checkpoint inhibitors have shown promise as second- or third-line treatments.