Treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis: a comprehensive review

Abstract

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease, characterised by persistent biliary inflammation resulting in fibrosis and multifocal strictures of the biliary tree. The course of disease is highly variable, ranging from asymptomatic disease to the development of end-stage biliary cirrhosis and an increased risk of biliary tract cancer (BTC), particularly cholangiocarcinoma (CCA).PSC is the most important risk factor for CCA in younger people, with a reported lifetime prevalence ranging from 6% to 13%. Perihilar CCA (pCCA), involving the hepatic duct bifurcation, is the most common CCA amounting to approximately 50% of all cases, whereas intrahepatic CCA (iCCA), located within the hepatic parenchyma, represents less than 10%.CCA is an aggressive tumour, and only a minority of patients are amenable to surgical resection with curative intent. Radical liver resection and liver transplantation are potentially curative therapeutic options in patients with PSC in the absence of metastatic or locally advanced disease. Liver transplantation with neoadjuvant chemoradiation could be considered in selected patients with unresectable pCCA and without pretreatment in patients with PSC with bile duct high-grade dysplasia. Recent reports demonstrating favourable outcomes in transplanted patients with small iCCA and patients with locally advanced disease following neoadjuvant therapy have challenged the previously described poor outcome in transplanted patients with iCCA.Treatment for CCA is challenged by the inherent difficulties in enabling an early diagnosis and thereby preventing an otherwise dismal prognosis. This comprehensive review aims to describe therapeutic considerations and challenges in patients with PSC-CCA.