Neoadjuvant therapy for cholangiocarcinoma: A comprehensive literature review.

Biliary tract cancers (BTCs) comprise a heterogenous group of aggressive and rare malignancies arising in the bile duct outside or within the liver. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC) and ampulla of Vater cancer (AVC); according to the "historical" anatomical classification, CCAs are further subdivided into extrahepatic cholangiocarcinomas (eCCAs) - including distal (dCCA) and perihilar (pCCA) - and intrahepatic cholangiocarcinomas (iCCA). Notably enough, these subtypes reflect distinct features in terms of biology, epidemiology, prognosis and therapeutic strategies. Although surgical resection remains the only potentially curative treatment option for CCA patients, radical surgery is possible for only a small proportion of cases. Moreover, it has been observed that up to 50% of patients deemed resectable at diagnosis are found to be unresectable during exploratory laparotomy. Additionally, even following radical surgery, recurrence rates are high. Neoadjuvant therapy represents an appealing approach in this setting, where this therapeutic strategy has the potential to improve local and distant control, to achieve R0 resection and to prevent distant metastasis. However, few data are currently available supporting neoadjuvant therapy in CCA and several questions remains unanswered, including the activity of systemic therapy in early stages of the disease, the optimal start time of treatment, patient selection and the length of neoadjuvant therapy. In this review, we will discuss available data on neoadjuvant systemic therapy in CCA, highlighting future directions in this setting, with a particular focus on recently published data and ongoing and recruiting trials.