Therapeutic Strategies for Hepatocellular Carcinoma: New Advances and Challenges

Hepatocellular carcinoma (HCC) is the fastest growing malignancy in the USA, and its prognosis remains poor with a 5-year survival around 12 %. Clinical data demonstrate that 85 % of cases occur in individuals with underlying cirrhosis and only 15 % develop in non-cirrhotic livers. Therefore, American and European guidelines recommend routine HCC screening for high-risk individuals (patients with cirrhosis) with abdominal ultrasound every 6 months. Once a lesion is identified or suspected on ultrasound, dynamic imaging is then indicated. The diagnosis of HCC is established in a patient with cirrhosis when a lesion measures at least 1 cm in diameter and demonstrates arterial enhancement and portal venous washout on contrast-enhanced computerized tomography or magnetic resonance imaging. Indeterminate lesions should be followed with surveillance imaging or further investigated with biopsy according to the level of suspicion for malignancy. Given the clinical, pathological, and molecular heterogeneity of HCC, there are multiple therapeutic modalities available. These may be curative, such as surgical resection, liver transplantation, and local ablation, or palliative, such as catheter-directed therapies (transarterial chemo, radio, or bland embolization), and systemic therapy (sorafenib). Patients with a single lesion, good performance status, and preserved liver synthetic function should be offered curative surgical resection or ablation therapy. Patients with HCC and decompensated liver disease should be evaluated and listed for liver transplantation. For unresectable disease or tumor burden precluding transplantation or curative ablation, palliative therapeutic modalities should be offered. Sorafenib is indicated for patients with vascular invasion and/or extra-hepatic metastasis if the estimated life expectancy is more than 3 months. Systemic internal radiation therapy using yttrium-90 microspheres in cases of multifocal bi-lobar disease and/or portal vein occlusion is an emerging therapy. Best supportive care is recommended for patients who lack the hepatic reserve to tolerate therapy.