Skip to main content
SpringerLink
Log in

Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma

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

Abstract

Introduction

Although preoperative α-fetoprotein (AFP) has been recognized as an important tumor marker among patients with hepatocellular carcinoma (HCC), the predictive value of AFP levels at the time of recurrence (rAFP) on post-recurrence outcomes has not been well examined.

Methods

Patients undergoing curative-intent resection of HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of rAFP on post-recurrence survival, as well as the impact of rAFP relative to the timing and treatment of HCC recurrence were examined.

Results

Among 852 patients who underwent resection of HCC, 307 (36.0%) individuals developed a recurrence. The median rAFP level was 8 ng/mL (interquartile range 3–100). Among the 307 patients who developed recurrence, 3-year post-recurrence survival was 48.5%. Patients with rAFP > 10 ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP < 10 ng/mL (28.7% vs. 65.5%, p < 0.001). rAFP correlated with survival among patients who had early (3-year survival; rAFP > 10 vs. < 10 ng/mL: 30.1% vs. 60.2%, p < 0.001) or late (18.0% vs. 78.7%, p = 0.03) recurrence. Furthermore, rAFP levels predicted 3-year post-recurrence survival among patients independent of the therapeutic modality used to treat the recurrent HCC (rAFP > 10 vs. < 10 ng/mL; ablation: 41.1% vs. 76.0%; intra-arterial therapy: 12.9% vs. 46.1%; resection: 37.5% vs. 100%; salvage transplantation: 60% vs. 100%; all p < 0.05). After adjusting for competing risk factors, patients with rAFP > 10 ng/mL had a twofold higher hazard of death in the post-recurrence setting (hazard ratio 1.96, 95% confidence interval 1.26–3.04).

Conclusion

AFP levels at the time of recurrence following resection of HCC predicted post-recurrence survival independent of the secondary treatment modality used. Evaluating AFP levels at the time of recurrence can help inform post-recurrence risk stratification of patients with recurrent 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
Fig. 3

Similar content being viewed by others

References

  1. Beal EW, Tumin D, Kabir A, et al. Trends in the mortality of hepatocellular carcinoma in the United States. J Gastrointest Surg. 2017;21(12):2033–8.

    Article  Google Scholar 

  2. Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol. 2018;68(3):526–49.

    Article  Google Scholar 

  3. Petrick JL, Kelly SP, Altekruse SF, McGlynn KA, Rosenberg PS. Future of hepatocellular carcinoma incidence in the United States forecast through 2030. J Clin Oncol. 2016;34(15):1787–94.

    Article  CAS  Google Scholar 

  4. Tsilimigras DI, Bagante F, Moris D, et al. Defining the chance of cure after resection for hepatocellular carcinoma within and beyond the Barcelona Clinic Liver Cancer guidelines: a multi-institutional analysis of 1,010 patients. Surgery. 2019;166(6):967–74.

    Article  Google Scholar 

  5. Pinna AD, Yang T, Mazzaferro V, et al. Liver transplantation and hepatic resection can achieve cure for hepatocellular carcinoma. Ann Surg. 2018;268(5):868–75.

    Article  Google Scholar 

  6. Chapman WC, Klintmalm G, Hemming A, et al. Surgical treatment of hepatocellular carcinoma in North America: can hepatic resection still be justified? J Am Coll Surg. 2015;220(4):628–37.

    Article  Google Scholar 

  7. Yang P, Si A, Yang J, et al. A wide-margin liver resection improves long-term outcomes for patients with HBV-related hepatocellular carcinoma with microvascular invasion. Surgery. 2019;165(4):721–30.

    Article  Google Scholar 

  8. Tsilimigras DI, Moris D, Hyer JM, et al. Hepatocellular carcinoma tumour burden score to stratify prognosis after resection. Br J Surg. 2020;107(7):854–64.

    Article  CAS  Google Scholar 

  9. Tabrizian P, Jibara G, Shrager B, Schwartz M, Roayaie S. Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg. 2015;261(5):947–55.

    Article  Google Scholar 

  10. Shah SA, Cleary SP, Wei AC, et al. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery. 2007;141(3):330–9.

    Article  Google Scholar 

  11. Chan AC, Chan SC, Chok KS, et al. Treatment strategy for recurrent hepatocellular carcinoma: salvage transplantation, repeated resection, or radiofrequency ablation? Liver Transpl. 2013;19(4):411–9.

    Article  Google Scholar 

  12. Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.

    Article  Google Scholar 

  13. Dimitroulis D, Damaskos C, Valsami S, et al. From diagnosis to treatment of hepatocellular carcinoma: an epidemic problem for both developed and developing world. World J Gastroenterol. 2017;23(29):5282–94.

    Article  Google Scholar 

  14. Ding HF, Zhang XF, Bagante F, et al. Prediction of tumor recurrence by α-fetoprotein model after curative resection for hepatocellular carcinoma. Eur J Surg Oncol. 2021;47(3 Pt B):660–6.

    Article  Google Scholar 

  15. European Association for the Study of the Liver. European Association for the Study of the Liver EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236.

    Article  Google Scholar 

  16. Tranchart H, Chirica M, Sepulveda A, et al. Long-term outcomes following aggressive management of recurrent hepatocellular carcinoma after upfront liver resection. World J Surg. 2012;36(11):2684–91.

    Article  Google Scholar 

  17. Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg. 1999;229(2):216–22.

    Article  CAS  Google Scholar 

  18. Tsilimigras DI, Mehta R, Guglielmi A, et al. Recurrence beyond the Milan criteria after curative-intent resection of hepatocellular carcinoma: a novel tumor-burden based prediction model. J Surg Oncol. 2020;122(5):955–63.

    PubMed  Google Scholar 

  19. Tsilimigras DI, Bagante F, Moris D, et al. Recurrence patterns and outcomes after resection of hepatocellular carcinoma within and beyond the barcelona clinic liver cancer criteria. Ann Surg Oncol. 2020;27(7):2321–31.

    Article  Google Scholar 

  20. Chen WT, Chau GY, Lui WY, et al. Recurrent hepatocellular carcinoma after hepatic resection: prognostic factors and long-term outcome. Eur J Surg Oncol. 2004;30(4):414–20.

    Article  Google Scholar 

  21. Kishi Y, Saiura A, Yamamoto J, et al. Repeat treatment for recurrent hepatocellular carcinoma: is it validated? Langenbecks Arch Surg. 2011;396(7):1093–100.

    Article  Google Scholar 

  22. Tsilimigras DI, Mehta R, Paredes AZ, et al. Overall tumor burden dictates outcomes for patients undergoing resection of multinodular hepatocellular carcinoma beyond the Milan criteria. Ann Surg. 2020;272(4):574–81.

    Article  Google Scholar 

  23. Ho CM, Lee PH, Shau WY, Ho MC, Wu YM, Hu RH. Survival in patients with recurrent hepatocellular carcinoma after primary hepatectomy: comparative effectiveness of treatment modalities. Surgery. 2012;151(5):700–9.

    Article  Google Scholar 

  24. Lee PH, Lin WJ, Tsang YM, et al. Clinical management of recurrent hepatocellular carcinoma. Ann Surg. 1995;222(5):670–6.

    Article  CAS  Google Scholar 

  25. Cha C, Fong Y, Jarnagin WR, Blumgart LH, DeMatteo RP. Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg. 2003;197(5):753–8.

    Article  Google Scholar 

  26. Bhangui P, Allard MA, Vibert E, et al. Salvage versus primary liver transplantation for early hepatocellular carcinoma: do both strategies yield similar outcomes? Ann Surg. 2016;264(1):155–63.

    Article  Google Scholar 

  27. Roayaie S, Bassi D, Tarchi P, Labow D, Schwartz M. Second hepatic resection for recurrent hepatocellular cancer: a Western experience. J Hepatol. 2011;55(2):346–50.

    Article  Google Scholar 

  28. Trevisani F, Garuti F, Neri A. Alpha-fetoprotein for diagnosis, prognosis, and transplant selection. Semin Liver Dis. 2019;39(2):163–77.

    Article  CAS  Google Scholar 

  29. Galle PR, Foerster F, Kudo M, et al. Biology and significance of alpha-fetoprotein in hepatocellular carcinoma. Liver Int. 2019;39(12):2214–29.

    Article  Google Scholar 

  30. Gelli M, Sebagh M, Porcher R, et al. Liver resection for early hepatocellular carcinoma: preoperative predictors of non transplantable recurrence and implications for treatment allocation. Ann Surg. 2020;272(5):820–6.

    Article  Google Scholar 

  31. Lee J, Joo I, Lee DH, Jeon SK, Lee JM. Clinical outcomes of patients with a high alpha-fetoprotein level but without evident recurrence on CT or MRI in surveillance after curative-intent treatment for hepatocellular carcinoma. Abdom Radiol (NY). 2020;46(2):597–606.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Diamantis I. Tsilimigras MD, Dimitrios Moris MD, J. Madison Hyer MS, Fabio Bagante MD & Timothy M. Pawlik MD, MPH, PhD, FACS, FRACS (Hon.)

  2. Department of Surgery, University of Verona, Verona, Italy

    Fabio Bagante MD & Alfredo Guglielmi MD

  3. Department of Surgery, Ospedale San Raffaele, Milan, Italy

    Francesca Ratti MD & Luca Aldrighetti MD

  4. Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal

    Hugo P. Marques MD

  5. Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France

    Olivier Soubrane MD

  6. Department of Surgery, Westmead Hospital, Sydney, NSW, Australia

    Vincent Lam MD

  7. Department of Surgery, Stanford University, Stanford, CA, USA

    George A. Poultsides MD

  8. Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania

    Irinel Popescu MD & Sorin Alexandrescu MD

  9. Department of Surgery, University of Ottawa, Ottawa, ON, Canada

    Guillaume Martel MD & Aklile Workneh MD

  10. Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia

    Tom Hugh MD

  11. Yokohama City University School of Medicine, Yokohama, Japan

    Itaru Endo MD, PhD

  12. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University, Columbus, OH, USA

    Timothy M. Pawlik MD, MPH, PhD, FACS, FRACS (Hon.)

Authors
  1. Diamantis I. Tsilimigras MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dimitrios Moris MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Madison Hyer MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fabio Bagante MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesca Ratti MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hugo P. Marques MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Olivier Soubrane MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vincent Lam MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. George A. Poultsides MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Irinel Popescu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sorin Alexandrescu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Guillaume Martel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Aklile Workneh MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Alfredo Guglielmi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Tom Hugh MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Luca Aldrighetti MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Itaru Endo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Timothy M. Pawlik MD, MPH, PhD, FACS, FRACS (Hon.)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy M. Pawlik MD, MPH, PhD, FACS, FRACS (Hon.).

Ethics declarations

Disclosure

Diamantis I. Tsilimigras, Dimitrios Moris, J. Madison Hyer, Fabio Bagante, Francesca Ratti, Hugo P. Marques, Olivier Soubrane, Vincent Lam, George A. Poultsides, Irinel Popescu, Sorin Alexandrescu, Guillaume Martel, Aklile Workneh, Alfredo Guglielmi, Tom Hugh, Luca Aldrighetti, Itaru Endo, and Timothy M. Pawlik have no conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsilimigras, D.I., Moris, D., Hyer, J.M. et al. Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma. Ann Surg Oncol 28, 7673–7683 (2021). https://doi.org/10.1245/s10434-021-09977-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-021-09977-x

Search

Navigation