Cholangiocarcinoma Therapeutics: An Update

Background: Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer and associated with a poor prognosis. Only one-third of CCA cases are diagnosed at oper-able stages. However, a high rate of relapse has been observed postoperatively. Besides screening for operable individuals, efficacious therapeutic for recurrent and advanced CCA is urgently need-ed. The treatment outcome of available therapeutics is important to clarify clinical indication and facilitate the development of treatment strategies. Objective: This review aims to compare the treatment outcome of different therapeutics based on both overall survival and progression-free survival. Methods: Over one hundred peer-reviewed articles were examined. We compared the treatment outcome between different treatment methods, including tumor resection with or without postopera-tive systematic therapy, chemotherapies including FOFLOX, and targeted therapies, such as IDH1, K-RAS, and FGFR inhibitors. Notably, the scientific basis and outcome of available treatment methods were compared with the standard first-line therapy. Results: CCAs at early stages should firstly undergo tumor resection surgery, followed by postoper-ative treatment with Capecitabine. Chemotherapy can be considered as a preoperative option for un-resectable CCAs. Inoperable CCAs with genetic aberrances like FGFR alterations, IDH1, and K-RAS mutations should be considered with targeted therapies. Fluoropyrimidine prodrug (S-1)/Gemcitabine/Cisplatin and nab-Paclitaxel/Gemcitabine/Cisplatin show favorable outcome which hints at the triplet regimen to be superior to Gemcitabine/Cisplatin on CCA. The triplet che-motherapeutic should be tested further compared to Gemcitabine/Cisplatin among CCAs without genetic alterations. Gemcitabine plus S-1 was recently suggested as the convenient and equivalent standard first-line for advanced/recurrent biliary tract cancer. Conclusion: This review provides a comparative outcome between novel targeted therapies and currently available therapeutics.