Skip to main content
Top
Published in: Annals of Surgical Oncology 12/2021

01-11-2021 | Hepatocellular Carcinoma | Hepatobiliary Tumors

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

Authors: Diamantis I. Tsilimigras, MD, Dimitrios Moris, MD, J. Madison Hyer, MS, Fabio Bagante, MD, Francesca Ratti, MD, Hugo P. Marques, MD, Olivier Soubrane, MD, Vincent Lam, MD, George A. Poultsides, MD, Irinel Popescu, MD, Sorin Alexandrescu, MD, Guillaume Martel, MD, Aklile Workneh, MD, Alfredo Guglielmi, MD, Tom Hugh, MD, Luca Aldrighetti, MD, Itaru Endo, MD, PhD, Timothy M. Pawlik, MD, MPH, PhD, FACS, FRACS (Hon.)

Published in: Annals of Surgical Oncology | Issue 12/2021

Login to get access

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.
Literature
1.
go back to reference 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.CrossRef 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.CrossRef
2.
go back to reference 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.CrossRef 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.CrossRef
3.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference 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.CrossRef 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.CrossRef
5.
go back to reference 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.CrossRef 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.CrossRef
6.
go back to reference 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.CrossRef 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.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.CrossRef Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.CrossRef
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference 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.CrossRef 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.CrossRef
16.
go back to reference 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.CrossRef 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.CrossRef
17.
go back to reference 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.CrossRef 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.CrossRef
18.
go back to reference 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 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
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference 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.CrossRef 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.CrossRef
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference 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.CrossRef 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.CrossRef
23.
go back to reference 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.CrossRef 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.CrossRef
24.
go back to reference Lee PH, Lin WJ, Tsang YM, et al. Clinical management of recurrent hepatocellular carcinoma. Ann Surg. 1995;222(5):670–6.CrossRef Lee PH, Lin WJ, Tsang YM, et al. Clinical management of recurrent hepatocellular carcinoma. Ann Surg. 1995;222(5):670–6.CrossRef
25.
go back to reference 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.CrossRef 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.CrossRef
26.
go back to reference 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.CrossRef 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.CrossRef
27.
go back to reference 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.CrossRef 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.CrossRef
28.
go back to reference Trevisani F, Garuti F, Neri A. Alpha-fetoprotein for diagnosis, prognosis, and transplant selection. Semin Liver Dis. 2019;39(2):163–77.CrossRef Trevisani F, Garuti F, Neri A. Alpha-fetoprotein for diagnosis, prognosis, and transplant selection. Semin Liver Dis. 2019;39(2):163–77.CrossRef
29.
go back to reference Galle PR, Foerster F, Kudo M, et al. Biology and significance of alpha-fetoprotein in hepatocellular carcinoma. Liver Int. 2019;39(12):2214–29.CrossRef Galle PR, Foerster F, Kudo M, et al. Biology and significance of alpha-fetoprotein in hepatocellular carcinoma. Liver Int. 2019;39(12):2214–29.CrossRef
30.
go back to reference 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.CrossRef 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.CrossRef
31.
go back to reference 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.CrossRef 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.CrossRef
Metadata
Title
Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma
Authors
Diamantis I. Tsilimigras, MD
Dimitrios Moris, MD
J. Madison Hyer, MS
Fabio Bagante, MD
Francesca Ratti, MD
Hugo P. Marques, MD
Olivier Soubrane, MD
Vincent Lam, MD
George A. Poultsides, MD
Irinel Popescu, MD
Sorin Alexandrescu, MD
Guillaume Martel, MD
Aklile Workneh, MD
Alfredo Guglielmi, MD
Tom Hugh, MD
Luca Aldrighetti, MD
Itaru Endo, MD, PhD
Timothy M. Pawlik, MD, MPH, PhD, FACS, FRACS (Hon.)
Publication date
01-11-2021
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 12/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-021-09977-x

Other articles of this Issue 12/2021

Annals of Surgical Oncology 12/2021 Go to the issue