Primary liver cancer: Prognostic factors and predictive response to therapy

Primary liver cancer (PLC) is the fifth most common cancer in men and the seventh most common cancer in women. Up to 85% of cases occur in developing countries. Liver cancer is associated with a high mortality rate that is similar across various geographic regions. Hepatocellular carcinoma (HCC) accounts for up to 85% of all PLC cases. Usually HCC is a consequence of cirrhosis, but it can also develop in the absence of chronic hepatic disease in approximately 20% of patients, especially among those with more severe forms of non-alcoholic fatty liver disease (NAFLD). Currently, both Western and Eastern guidelines recommend only radiological diagnosis in patients with cirrhosis. The most widely accepted system is the Barcelona Clinic Liver Cancer (BCLC) staging system, which was updated in 2011 and was validated by several groups in Western countries. The BCLC staging system includes factors of both tumor morphology and degree of impairment of liver function, and it can be used to assign the proper treatment to patients with HCC. However, these treatment allocations have been criticized due to the exclusion from surgical resection of some patients who could potentially benefit from this type of therapy. The treatment of HCC varies in relation to the tumor stage and the degree of hepatic dysfunction. Liver transplantation and surgical resection with radical intent enables good long-term survival and excellent 5-year survival rates (70-50%). In addition, locoregional treatment can also achieve positive results, especially treatment of early-stage nodules. Intrahepatic cholangiocarcinoma (ICC), the second most common primary liver cancer after HCC, arises from the bile ducts of the second-order and usually presents as a mass inside the liver. CT and MRI imaging are the most useful imaging modalities for the diagnosis of ICC: imaging techniques show the location of the tumor, the possible multifocality of the lesion, the presence of venous or arterial invasion, and the presence of lymphnode involvement or distant metastases. According to the type of macroscopic growth, three types of ICC are described: mass forming (MF), periductal infiltrating (PI), and intraductal growing (IG). Radical surgical resection (R0) is the treatment of choice and the only one able to achieve long-term survival. In order to achieve radical resection, a major hepatectomy is often required, but this therapeutic option still has acceptable mortality and morbidity rates. Other PLCs (e.g., fibrolamellar hepatocellular carcinoma, epithelioid hemangioendothelioma, hepatoblastoma, sarcoma and lymphomas, combined HCC and ICC) are very rare, and surgery is the treatment of choice for these types of PLCs.