Cholangiocellular Carcinoma.

BACKGROUND: Cholangiocarcinomas (CCAs) are aggressive malignancies that display features of biliary differentiation. According to their anatomical location, CCAs are commonly classified as intrahepatic and extrahepatic tumors, the latter entity being further subdivided into perihilar CCAs, also termed as Klatskin tumors, and distal tumors. While a majority of CCAs occur sporadically, established risk factors such as liver fluke infestation or primary sclerosing cholangitis exist.
SUMMARY: Due to lack of efficient early screening markers, CCAs are frequently diagnosed at an advanced stage when curative surgical resection is not an option. Chemotherapy with gemcitabine and cisplatin is currently the standard palliative treatment that prolongs overall survival by 3.6 months as compared to monotherapy with gemcitabine. For CCA patients who progress under gemcitabine/cisplatin, the paucity of prospective, randomized trials is detrimental, and there is currently no recommended second-line regimen with respect to chemotherapy or loco-regional treatment modalities. Molecular profiling of CCAs supports the implementation of targeted approaches, and it is reasonable that personalized therapy will become a mainstay of CCA treatment. In addition, the advent of immunotherapy holds considerable promise, yet, similar to targeted treatment, needs to be prospectively evaluated in clinically and genetically thoroughly characterized patients. KEY POINTS: (1) CCA is a genetically diverse and highly aggressive malignancy. (2) Gemcitabine in combination with cisplatin or oxaliplatin is the current first-line chemotherapy in non-resectable patients. (3) Loco-regional treatment modalities exist but need to be evaluated in prospective randomized trials in the context of systemic chemotherapy. (4) Targeted therapies in molecularly defined subgroups of patients and immunotherapies alone or in combinations will most likely improve survival in the future.