Skip to main content
SpringerLink
Log in

Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT).

Methods

All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival.

Results

Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p = 0.02) and tumor burden (p < 0.001). The majority of those listed underwent LT (n = 69, 72%). Both tumor progression on waiting list (hazard ratio [HR] 4.973; range1.599–15.464; p = 0.006) and peak alpha-fetoprotein (AFP) at 400 ng/ml or higher (HR, 4.604; range 1.660–12.768; p = 0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% of the patients (n = 24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p = 0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93, 71, and 66%.

Conclusion

Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bruix J, Sherman M, American Association for the Study of Liver D. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.

    Article  PubMed  PubMed Central  Google Scholar 

  2. European Association for the Study of the L, European Organisation for R, Treatment of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.

    Article  Google Scholar 

  3. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.

    Article  CAS  PubMed  Google Scholar 

  4. Mazzaferro V, Bhoori S, Sposito C, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44–57.

    Article  PubMed  Google Scholar 

  5. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394–403.

    Article  CAS  PubMed  Google Scholar 

  6. Yao FY, Xiao L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007;7:2587–96.

    Article  CAS  PubMed  Google Scholar 

  7. Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 2016;150:835–53.

    Article  PubMed  Google Scholar 

  8. Iwatsuki S, Gordon RD, Shaw BW Jr, Starzl TE. Role of liver transplantation in cancer therapy. Ann Surg. 1985;202:401–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–9.

    Article  PubMed  Google Scholar 

  10. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–71.

    Article  CAS  PubMed  Google Scholar 

  11. Cillo U, Giuliani T, Polacco M, et al. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol. 2016;22:232–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sapisochin G, Goldaracena N, Laurence JM, et al. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: a prospective validation study. Hepatology. 2016;64:2077–88.

    Article  PubMed  Google Scholar 

  13. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.

    Article  CAS  PubMed  Google Scholar 

  14. Sandroussi C, Dawson LA, Lee M, et al. Radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma. Transpl Int. 2010;23:299–306.

    Article  PubMed  Google Scholar 

  15. Toso C, Meeberg G, Hernandez-Alejandro R, et al. Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: a prospective validation. Hepatology. 2015;62:158–65.

    Article  CAS  PubMed  Google Scholar 

  16. Yang P, Zeng ZC, Wang BL, et al. The degree of Lipiodol accumulation can be an indicator of successful treatment for unresectable hepatocellular carcinoma (HCC) patients—in the case of transcatheter arterial chemoembolization (TACE) and external beam radiotherapy (EBRT). J Cancer. 2016;7:1413–20.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zhao Y, Li H, Bai W, et al. Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: a multicenter clinical study of 606 HCC patients. Int J Cancer. 2016;139:928–37.

    Article  CAS  PubMed  Google Scholar 

  18. Lencioni R, Llovet JM, Han G, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol. 2016;64:1090–8.

    Article  CAS  PubMed  Google Scholar 

  19. Lance C, McLennan G, Obuchowski N, et al. Comparative analysis of the safety and efficacy of transcatheter arterial chemoembolization and yttrium-90 radioembolization in patients with unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2011;22:1697–705.

    Article  PubMed  Google Scholar 

  20. Moreno-Luna LE, Yang JD, Sanchez W, et al. Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2013;36:714–23.

    Article  PubMed  Google Scholar 

  21. El Fouly A, Ertle J, El Dorry A, et al. In intermediate-stage hepatocellular carcinoma: radioembolization with yttrium-90 or chemoembolization? Liver Int. 2015;35:627–35.

    Article  PubMed  Google Scholar 

  22. Thein HH, Isaranuwatchai W, Campitelli MA, et al. Health care costs associated with hepatocellular carcinoma: a population-based study. Hepatology. 2013;58:1375–84.

    Article  PubMed  Google Scholar 

  23. Belli LS, Berenguer M, Cortesi PA, et al. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: a European study. J Hepatol. 2016;65:524–31.

    Article  PubMed  Google Scholar 

  24. Mazzaferro V. Squaring the circle of selection and allocation in liver transplantation for HCC: an adaptive approach. Hepatology. 2016;63:1707–17.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10:686–90.

    Article  CAS  PubMed  Google Scholar 

  26. Olthoff KM, Smith AR, Abecassis M, et al. Defining long-term outcomes with living donor liver transplantation in North America. Ann Surg. 2015;262:465–75, discussion 473–465.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Selzner M, Kashfi A, Cattral MS, et al. Live donor liver transplantation in high MELD score recipients. Ann Surg. 2010;251:153–7.

    Article  PubMed  Google Scholar 

  28. Rossler F, Sapisochin G, Song G, et al. Defining benchmarks for major liver surgery: a multicenter analysis of 5202 living liver donors. Ann Surg. 2016;264:492–500.

    Article  PubMed  Google Scholar 

  29. Bittermann T, Niu B, Hoteit MA, Goldberg D. Waitlist priority for hepatocellular carcinoma beyond milan criteria: a potentially appropriate decision without a structured approach. Am J Transplant. 2014;14:79–87.

    Article  CAS  PubMed  Google Scholar 

  30. Schmitt TM, Kumer SC, Shah N, et al. Liver transplantation for T3 lesions has higher waiting list mortality but similar survival compared to T1 and T2 lesions. Ann Hepatol. 2010;9:390–6.

    PubMed  Google Scholar 

  31. Mehta N, Sarkar M, Dodge JL, et al. Intention to treat outcome of T1 hepatocellular carcinoma with the “wait and not ablate” approach until meeting T2 criteria for liver transplant listing. Liver Transpl. 2016;22:178–87.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Vitale A, D’Amico F, Frigo AC, et al. Response to therapy as a criterion for awarding priority to patients with hepatocellular carcinoma awaiting liver transplantation. Ann Surg Oncol. 2010;17:2290–302.

    Article  PubMed  Google Scholar 

  33. Merani S, Majno P, Kneteman NM, et al. The impact of waiting list alpha-fetoprotein changes on the outcome of liver transplant for hepatocellular carcinoma. J Hepatol. 2011;55:814–9.

    Article  CAS  PubMed  Google Scholar 

  34. Sapisochin G, Goldaracena N, Astete S, et al. Benefit of treating hepatocellular carcinoma recurrence after liver transplantation and analysis of prognostic factors for survival in a large Euro-American series. Ann Surg Oncol. 2015;22:2286–94.

    Article  CAS  PubMed  Google Scholar 

  35. Bodzin AS, Lunsford KE, Markovic D, et al. Predicting mortality in patients developing recurrent hepatocellular carcinoma after liver transplantation: impact of treatment modality and recurrence characteristics. Ann Surg. 2016.

  36. Yao FY. Liver transplantation for hepatocellular carcinoma: beyond the Milan criteria. Am J Transplant. 2008;8:1982–9.

    Article  CAS  PubMed  Google Scholar 

  37. Toso C, Mentha G, Kneteman NM, Majno P. The place of downstaging for hepatocellular carcinoma. J Hepatol. 2010;52:930–6.

    Article  PubMed  Google Scholar 

  38. Roberts JP, Venook A, Kerlan R, Yao F. Hepatocellular carcinoma: ablate and wait versus rapid transplantation. Liver Transpl. 2010;16:925–9.

    Article  PubMed  Google Scholar 

  39. Pomfret EA, Washburn K, Wald C, et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl. 2010;16:262–78.

    Article  PubMed  Google Scholar 

  40. Mulligan DC. The ongoing quest to find the appropriate patients to transplant with hepatocellular carcinoma: Milan to San Francisco to Toronto and beyond. Hepatology. 2016;64:1853–55.

    Article  PubMed  Google Scholar 

  41. Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43.

    Article  PubMed  Google Scholar 

  42. Lee HW, Suh KS. Liver transplantation for advanced hepatocellular carcinoma. Clin Mol Hepatol. 2016;22:309–18.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Moray G, Karakayali F, Yilmaz U, et al. Expanded criteria for hepatocellular carcinoma and liver transplantation. Transplant Proc. 2007;39:1171–4.

    Article  CAS  PubMed  Google Scholar 

Download references

Disclosure

There are no conflicts of interest.

Author information

Authors and Affiliations

  1. Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Canada

    Aloysious D. Aravinthan MBBS, MRCP, MRCP (Gastroenterology), PhD, Adam C. Doyle MD, Nicolas Goldaracena MD, Assaf Issachar MD, Leslie B. Lilly MSc, MD, FRCPC, Nazia Selzner MD, PhD, Mamatha Bhat MD, MSc, FRCPC, Boraiah Sreeharsha MD, Markus Selzner MD, Anand Ghanekar MD, PhD, FRCSC, Mark S. Cattral MD, MSc, FRCSC, Ian D. McGilvray MD, FRCSC, PhD, Paul D. Greig MD, FRCSC, FACS, Eberhard L. Renner MD, FRCPC, David R. Grant MD, FRCSC & Gonzalo Sapisochin MD

  2. National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK

    Aloysious D. Aravinthan MBBS, MRCP, MRCP (Gastroenterology), PhD

  3. Department of Medical Imaging, University of Toronto, Toronto, Canada

    Silvio G. Bruni MD

  4. Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

    Hla-Hla Thein MD, MPH, PhD

  5. Department of Medicine, Max Rady College of Medicine/Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Eberhard L. Renner MD, FRCPC

  6. Abdominal Transplant & HPB Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, ON, Canada

    Gonzalo Sapisochin MD

Authors
  1. Aloysious D. Aravinthan MBBS, MRCP, MRCP (Gastroenterology), PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvio G. Bruni MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adam C. Doyle MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hla-Hla Thein MD, MPH, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicolas Goldaracena MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Assaf Issachar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Leslie B. Lilly MSc, MD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nazia Selzner MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mamatha Bhat MD, MSc, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Boraiah Sreeharsha MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Markus Selzner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Anand Ghanekar MD, PhD, FRCSC
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Mark S. Cattral MD, MSc, FRCSC
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ian D. McGilvray MD, FRCSC, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Paul D. Greig MD, FRCSC, FACS
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Eberhard L. Renner MD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. David R. Grant MD, FRCSC
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Gonzalo Sapisochin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gonzalo Sapisochin MD.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 34 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aravinthan, A.D., Bruni, S.G., Doyle, A.C. et al. Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma. Ann Surg Oncol 24, 1843–1851 (2017). https://doi.org/10.1245/s10434-017-5789-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-017-5789-3

Keywords

Search

Navigation