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Intermediate-stage HCC—upfront resection can be feasible

Nature Reviews Clinical Oncology volume 12, page 295 (2015)Cite this article

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We read with great interest the Review by Forner et al. (Treatment of intermediate-stage hepatocellular carcinoma. Nat. Rev. Clin. Oncol. 11, 525–535; 2014),1 which focused on the definition of and treatment options for intermediate-stage hepatocellular carcinoma (HCC). Their definition appropriately accounts for the clinical heterogeneity of intermediate-stage HCC, and we applaud their recommendation that disease involving a single large tumour (>5 cm) without vascular invasion should be classified as early-stage disease,1 which contrasts with previous articles from the Barcelona Clinic Liver Cancer (BCLC) group.2 We also applaud their suggestion that patients with a single large tumour (>5 cm) and no vascular invasion can benefit from hepatic resection, when technically feasible.1 This article, written by members of the highly influential BCLC group, might help advance HCC treatment by updating diagnostic guidelines and providing tentative support for less restrictive use of hepatic resection. At the same time, the Review contains some statements regarding the treatment of intermediate-stage HCC that might not adequately reflect the available clinical evidence; these statements, in our opinion, overemphasize the appropriateness of transarterial chemoembolization (TACE) and sorafenib therapy, and severely underestimate the usefulness of hepatic resection.

Forner et al.1 indicate that TACE should be considered as the first-line treatment option for patients with intermediate-stage HCC, and that patients for whom TACE is contraindicated or proves unsuccessful can be considered for sorafenib therapy or radioembolization. Although the authors are correct that TACE is widely accepted in clinical guidelines as the first-line therapy for patients with intermediate-stage HCC, this treatment has not been consistently associated with a survival benefit across a wide range of studies conducted in several countries. Studies demonstrating a survival benefit have compared TACE with best supportive care;3 however, no benefit has been observed in studies comparing TACE with hepatic resection.4 In addition, TACE outcomes depend strongly on the specific techniques and chemoembolization agents used. Indeed, in a Cochrane systematic review article published in 2011,5 it was concluded that the available evidence does not clearly argue for or against the use of TACE for the treatment of patients with unresectable HCC. Moreover, some absolute and relative contraindications for TACE exist; as guidelines from Japan, Europe and the BCLC group itself indicate, not all patients with intermediate-stage HCC are eligible for TACE, nor do they all benefit from this treatment.1,6,7 Moreover, the optimal criteria for selecting patients for TACE, for scheduling of repeat treatments, and for the termination of treatment remain unknown. Furthermore, TACE is associated with a wide range of adverse events.5

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References

  1. Forner, A., Gilabert, M., Bruix, J. & Raoul, J. L. Treatment of intermediate-stage hepatocellular carcinoma. Nat. Rev. Clin. Oncol. 11, 525–535 (2014).

    Article  CAS  Google Scholar 

  2. Llovet, J. M., Brú, C. & Bruix, J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin. Liver. Dis. 19, 329–338 (1999).

    Article  CAS  Google Scholar 

  3. Llovet, J. M. & Bruix, J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37, 429–442 (2003).

    Article  CAS  Google Scholar 

  4. Zhong, J. H. et al. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma. Ann. Surg. 260, 329–340 (2014).

    Article  Google Scholar 

  5. Oliveri, R. S., Wetterslev, J. & Gluud, C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD004787. http://dx.doi.org/10.1002/14651858.CD004787.pub2 (2011).

  6. Kudo, M. et al. Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig. Dis. 29, 339–364 (2011).

    Article  Google Scholar 

  7. European Association for The Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL–EORTC clinical practice guidelines: management of hepatocellular carcinoma. J. Hepatol. 56, 908–943 (2012).

  8. Malagari, K. et al. Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis. Cardiovasc. Intervent. Radiol. 35, 1119–1128 (2012).

    Article  Google Scholar 

  9. Burrel, M. et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using drug eluting beads. Implications for clinical practice and trial design. J. Hepatol. 56, 1330–1335 (2012).

    Article  Google Scholar 

  10. Salem, R. et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 138, 52–64 (2010).

    Article  CAS  Google Scholar 

  11. Bruix, J. et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J. Hepatol. 57, 821–829 (2012).

    Article  CAS  Google Scholar 

  12. Lencioni, R. et al. GIDEON (global investigation of therapeutic decisions in hepatocellular carcinoma and of its treatment with sorafenib): second interim analysis. Int. J. Clin. Pract. 68, 609–617 (2014).

    Article  CAS  Google Scholar 

  13. Beaugrand, M. et al. Treatment of advanced hepatocellular carcinoma by seocalcitol (a vit D analogue): an international randomized double-blind placebo-controlled study in 747 patients [abstract 37]. J. Hepatol. 42 (Suppl. 2), 17 (2005).

    Google Scholar 

  14. Zhong, J. H., Wu, F. X & Li, H. Hepatic resection associated with good survival for selected patients with multinodular hepatocellular carcinoma. Tumour Biol. 35, 8355–8358 (2014).

    Article  Google Scholar 

  15. Yin, L. et al. Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan Criteria: a RCT. J. Hepatol. 61, 82–88 (2014).

    Article  Google Scholar 

  16. Zhong, J. H. et al. Hepatic resection as a safe and effective treatment for hepatocellular carcinoma involving a single large tumor, multiple tumors, or macrovascular invasion. Medicine (Baltimore) 94, e396 (2015).

    Article  CAS  Google Scholar 

  17. Zhong, J. H. et al. Hepatic resection is safe and effective for patients with hepatocellular carcinoma and portal hypertension. PLoS ONE 9, e108755 (2014).

    Article  Google Scholar 

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Acknowledgements

The authors thank Armando Chapin Rodríguez, PhD, for his language editing. The authors' research is supported by the Self-Raised Scientific Research Fund of the Ministry of Health of Guangxi Province (Z2014241), the Youth Science Foundation of Guangxi Medical University (GXMUYSF201302), the National Science and Technology Major Special Project (2012ZX10002010001009), and the National Natural Science Foundation of China (81160262/H1602).

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  1. Hepatobiliary Surgery Department, Affiliated Tumour Hospital of Guangxi Medical University, 71 He Di Road, 530021, Nanning, People's Republic of China

    Jian-Hong Zhong, Shi-Dong Lu, Yan-Yan Wang, Liang Ma & Le-Qun Li

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Correspondence to Jian-Hong Zhong or Le-Qun Li.

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Zhong, JH., Lu, SD., Wang, YY. et al. Intermediate-stage HCC—upfront resection can be feasible. Nat Rev Clin Oncol 12, 295 (2015). https://doi.org/10.1038/nrclinonc.2014.122-c3

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