Therapies for Advanced Stage Hepatocellular Carcinoma with Macrovascular invasion or Metastatic Disease: a Systematic Review and Meta-analysis

Abstract

Hepatocellular carcinoma (HCC) is a complex disease most commonly arising in the background of chronic liver disease. In the past two decades there has been a significant increase in our understanding of both the clinical and molecular heterogeneity of HCC. There has been a robust increase in clinical trial activity in patients with poor prognostic factors such as macrovascular invasion and extrahepatic spread. We aimed to synthesize the evidence for the treatment of patients with advanced HCC based on these baseline characteristics including patients with both Child-Pugh scores of A and B. A comprehensive search of several databases from each database inception to February 15th 2016, any language was conducted.We included 14 studies (3 randomized controlled studies (RCTs) and 11 observational studies).We included studies that compared sorafenib, transarterial bland embolisation/transarterial chemoembolization, yttrium-90/radiation therapy, ablation (or combination) and no therapy. Two RCTs comparing sorafenib to best supportive care demonstrated a consistent improvement in OS for patients with advanced HCC and MVI and/or EHS and Child Pugh-A liver disease (HR 0.66 (95% CI 0.51-0.87), I²= 0%). Several observational studies evaluated loco-regional therapies alone or in combination with other treatments and were limited by very low quality of evidence. This was true for both patients with EHS and MVI. Conclusion: In patients with advanced HCC and Child-Pugh A liver function, sorafenib is the only treatment that has been shown to improve overall survival in randomized studies. High quality data supporting the use of other treatment modalities in this setting, or in the setting of patients with less compensated (CP B) liver disease is lacking. This article is protected by copyright. All rights reserved.

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