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Treatment of intermediate-stage hepatocellular carcinoma

Key Points

  • A number of treatments are available for hepatocellular carcinoma (HCC), and their allocation—as well as disease prognosis—is influenced by tumour stage and the degree of liver-function impairment

  • The current definition of intermediate-stage HCC (Barcelona Clinic Liver Cancer [BCLC] stage B) is extensive multifocal disease confined to the liver, with preserved liver function and no cancer-related symptoms

  • Transarterial chemoembolization (TACE) is considered the standard treatment for intermediate-stage HCC in patients with preserved liver function and no cancer-related symptoms

  • Major efforts have been made to improve outcomes among patients treated with TACE; accurate technique together with appropriate patient selection is key to obtaining the best results

  • Sorafenib, the only systemic treatment associated with a survival benefit in HCC, should be considered for patients with BCLC stage B HCC who are not eligible for TACE

  • Radioembolization has antitumoural efficacy in patients with intermediate-stage HCC, but evidence of survival benefit has not been presented and is awaited

Abstract

Hepatocellular carcinoma (HCC)—closely associated with liver cirrhosis and, in fact, the main cause of death in patients with such disease—is now recognized as one of the most-prevalent and lethal neoplasms worldwide. Prognosis and allocation of the multiple available treatment options for patients with HCC are influenced not only by tumour stage, but also by the degree of liver-function impairment. Therefore, accurate assessment and classification of disease is important for patient management. According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, intermediate-stage HCC is defined as extensive multifocal disease without vascular invasion in patients with preserved liver function and absence of cancer-related symptoms; in this context, transarterial chemoembolization (TACE) is considered the standard treatment. The use of drug-eluting beads has enabled standardization of this procedure, resulting in higher reproducibility and tolerability of the treatment. Nevertheless, not all patients with intermediate-stage HCC are good candidates for TACE and, for such patients in whom TACE is not appropriate or has failed, other treatments can be considered, including sorafenib. Radioembolization is a promising alternative that deserves further prospective studies. Herein, we review the current approaches used to accurately stratify patients with intermediate-stage HCC and subsequently allocate the most-appropriate treatments. The key developments in therapeutic strategies are also discussed.

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Figure 1: BCLC staging and treatment strategy.1
Figure 2: Proposed treatment algorithm after first-line TACE therapy in patients with intermediate-stage HCC.

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Acknowledgements

The Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd; Networked Biomedical Research Centre for Hepatic and Digestive Diseases) is funded by the Instituto de Salud Carlos III. The Instituto de Salud Carlos III has also supported the work of A.F. and J.B. (grants PI11/01830 and PI13/01229).

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A.F., J.B. and J.-L.R. contributed to all stages of the preparation of the manuscript for submission. M.G. made substantial contributions researching data for article, discussion of content, and review/editing of the manuscript before submission.

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Correspondence to Jordi Bruix or Jean-Luc Raoul.

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Competing interests

A.F. has acted as a consultant for Bayer HealthCare. J.B. has acted as a consultant or in an advisory role for ArQule, Bayer, Biocompatibles, Bristol-Myers Squibb, Celgene, Daiichi-Sankyo, Kowa, Lilly, Novartis, Roche, and Terumo. J.-L.R. has acted as a consultant or in an advisory role for Arqule, Bayer HealthCare, Biocompatibles, Bristol-Myers Squibb, and Merck Serono. M.G. declares no competing interests.

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Forner, A., Gilabert, M., Bruix, J. et al. Treatment of intermediate-stage hepatocellular carcinoma. Nat Rev Clin Oncol 11, 525–535 (2014). https://doi.org/10.1038/nrclinonc.2014.122

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