Recent Advances in the Treatment of Hepatocellular Carcinoma

Amit G. Singal; Jorge A. Marrero

Disclosures

Curr Opin Gastroenterol. 2010;26(3):189-195. 

In This Article

Surgical Resection

Surgical resection is the treatment of choice for noncirrhotic patients with HCC. Most patients with HCC in the United States and Europe have underlying cirrhosis and are at risk for hepatic decompensation if they do not have adequate hepatic reserve. Therefore, surgical resection for these patients requires careful patient selection. The 5-year survival rates are only 25% in patients with significant portal hypertension and bilirubin levels more than 1 mg/dl, compared with 74% 5-year survival rates in patients without portal hypertension and normal bilirubin levels.[13] Resection is associated with a high risk of tumor recurrence, as high as 50% after 5 years, and therefore it has a limited efficacy in HCC.[14]

In a retrospective analysis of 788 patients with early HCC from the Surveillance, Epidemiology, and End Results (SEER) database, the median and 5-year survival after resection were 45 months and 39%, respectively.[15••] After adjusting for demographic factors and tumor grade, tumor size more than 2 cm (hazard ratio 1.51), multifocal tumors (hazard ratio 1.51), and vascular invasion (hazard ratio 1.44) were independent predictors of worse survival. The median survival was 70 months in the lowest risk patients compared with a median survival of 24 months in the highest risk patients. Resection can be successfully applied but should be limited to patients with small unifocal lesions.

A recent Cochrane review found 12 randomized controlled trials assessing the benefit of adjuvant or neoadjuvant therapy with resection.[16•] The risk of death was significantly reduced with neoadjuvant or adjuvant therapy in four studies but significantly increased in two others. Lower rates of recurrence were more consistently observed across the studies, although only three studies reported significant reductions in recurrence rates. Overall, the authors concluded that there is no strong evidence for any neoadjuvant or adjuvant regimens with resection and randomized controlled trials are necessary. Similarly, neoadjuvant transarterial chemoembolization (TACE) did not prolong survival in patients with resectable HCC and may result in larger rates of dropout due to progression of disease.[17] Two recent randomized controlled trials demonstrated a benefit for adjuvant TACE after resection in a subset of patients with portal vein tumor thrombus. In one trial, 126 patients with intermediate-stage HCC involving the portal vein were randomized to hepatectomy alone versus hepatectomy with adjuvant TACE 4–6 weeks after surgery. The median survival for those with hepatectomy alone was 9 months, compared with 13 months for those who received adjuvant TACE.[18] In the second trial, 115 patients with HCC involving the portal vein but with less than three nodules were randomized to hepatectomy and portal vein tumor thrombi removal versus hepatectomy with adjuvant TACE 3–4 weeks after surgery. The median survival after hepatectomy was 14 months, compared with a 23-month median survival in those who received adjuvant TACE.[19] Given that these patients had more tumor burden that what is recommended for resection, it is unclear whether this benefit would have been seen with TACE alone.

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