Neoadjuvant chemotherapy alone or combined with trans-arterial therapies for downstaging unresectable intrahepatic cholangiocarcinoma to surgical resection: a narrative review

Intrahepatic cholangiocarcinoma (ICCA) incidence has been rising in the last few decades. Currently, hepatic resection is the only curative treatment for ICCA, and there is a lack of evidence supporting the use of preoperative treatment. A narrative review was conducted to analyze the available literature published on the role of neoadjuvant chemotherapy (CHT), either alone or combined with intra-arterial therapies (IAT), for downstaging unresectable ICCA to surgical resection. Most of the studies included in this review showed that secondary resection was associated with improvement in overall survival. In particular, studies analyzing CHT alone reported the highest conversion rate ranging from 20% to 57.1%, confirming that systemic treatment may yield the best results, and therefore, it should always be included as part of the neoadjuvant protocol. Among all the IATs, the longest overall survival reported was after CHT plus hepatic artery infusion, 25 months. Downsizing neoadjuvant multimodal approach, including combined systemic therapy with IAT, might improve the long-term outcomes of unresectable patients and expand surgical indications. However, randomized controlled trials are necessary to confirm their effectiveness.