Localized and systemic approaches to treating hepatocellular carcinoma.

Abstract

Although hepatocellular carcinoma (HCC) is the sixth most common cancer globally, the overall outcomes are poor with 5-year overall survival (OS) rates estimated at less than 12%. Relatively few patients are eligible for curative therapy because of the late appearance of symptoms despite the established efficacy of screening programs in at-risk individuals. Unlike other high-incidence malignancies, therapeutic decisions in HCC are hampered by the limits of high-quality evidence across all clinical scenarios. The selection of treatment modalities depends not only on the stage, the extent of tumor, and the patient’s performance status but also on the underlying liver function. The Barcelona Clinic Liver Cancer (BCLC) classification stratifies patients according to these factors and provides treatment recommendations (Fig 1), but it may oversimplify decision making that is best approached through multidisciplinary case discussions. Surgery or transplantation remain the mainstays of curative therapy for early disease. Ablative strategies can also cure small tumors. Transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and external beam radiation therapy (EBRT) can control locally advanced disease no longer amenable to cure. Systemic treatment for advanced HCC was not recognized as a standard until the approval of sorafenib for a modest improvement in median OS. This discovery resulted in a plethora of clinical trials aimed at advancing the field. Many targeted therapies are being explored as firstor second-line treatment options in advanced HCC, although results to date have been disappointing. Because more than 90% of cancers arise in patients with underlying cirrhosis, the treatment of HCC requires the management of both the concurrent malignancy and liver disease. Many patients presenting with HCC will require ongoing supportive care of their underlying liver disease such as hepatitis B virus (HBV) or hepatitis C virus (HCV) infections or nonalcoholic steatohepatitis. Because these conditions may also complicate cancer treatment strategies (eg, with a high risk for reactivation of HBV around most cancer treatments), antiviral therapy for active infection should be considered a standard of care. Because HCV does not generally reactivate around cancer treatments, dedicated therapy is not necessary. However, the current advancements in new direct-acting antivirals such as sofosbuvir and others are so effective that shorter courses of therapy are associated with high sustained HCV response rates with relatively few toxicities. It is expected that patients with HCV will be treated early for viral clearance precirrhosis, even if they present later with HCC.