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Medical therapies for hepatocellular carcinoma: a critical view of the evidence

Abstract

The management of hepatocellular carcinoma (HCC) has substantially changed in the past few decades. Improvements in patient stratification (for example, using the Barcelona Clinic Liver Cancer staging system) and the introduction of novel therapies (such as sorafenib) have improved patient survival. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. Decision-making largely relies on evidence-based criteria, as depicted in the US and European clinical practice guidelines, which endorse five therapeutic recommendations: resection; transplantation; radiofrequency ablation; chemoembolization; and sorafenib. However, areas still exist in which uncertainty precludes a strong recommendation, such as the role of adjuvant therapies after resection, radioembolization with yttrium-90 or second-line therapies for advanced HCC. Many clinical trials that are currently ongoing aim to answer these questions. The first reported studies, however, failed to identify novel therapeutic alternatives (that is, sunitinib, erlotinib or brivanib). Moreover, genomic profiling has enabled patient classification on the basis of molecular parameters, and has facilitated the development of new effective drugs. However, no oncogene addiction loops have been identified so far, as has been the case with other cancers such as melanoma, lung or breast cancer. Efforts that focus on the implementation of personalized medicine approaches in HCC will probably dominate research in the next decade.

Key Points

  • Epidemiological data indicate that the disease burden of hepatocellular carcinoma (HCC) is increasing worldwide, both in terms of incidence and mortality

  • The Barcelona Clinic Liver Cancer staging system provides a general framework for decision-making in patients with HCC, and facilitates stage-based unified selection criteria for clinical trials

  • Evidence-based criteria dominate recommendations for HCC management, enabling stratification of evidence according to scientific standards and providing a hierarchy of medical recommendations

  • Five treatments are strongly recommended in HCC on the basis of evidence-based data: resection; liver transplantation; radiofrequency ablation; chemoembolization; and sorafenib

  • Sorafenib, a molecular targeted agent, prolongs survival in patients with advanced HCC and is the sole systemic drug that is proved to be effective in this disease

  • No oncogenic addiction loops have so far been identified in HCC; research initiatives should aim to identify subgroups of patients with targetable dominant molecular alterations

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Figure 1: BCLC staging system and therapeutic strategy according to EASL–EORTC guidelines.
Figure 2: Therapeutic interventions in HCC according to level of evidence and grade of recommendation.

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J. M. Llovet has acted as a consultant for Bayer Pharmaceutical, Biocompatibles, Bristol–Myer–Squibb and ImClone. In addition, he has received grant or research support from Bayer Pharmaceutical and Bristol–Myer–Squibb. The other authors declare no competing interests.

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Villanueva, A., Hernandez-Gea, V. & Llovet, J. Medical therapies for hepatocellular carcinoma: a critical view of the evidence. Nat Rev Gastroenterol Hepatol 10, 34–42 (2013). https://doi.org/10.1038/nrgastro.2012.199

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