Synergistic impact of alpha‐fetoprotein and tumor burden on long‐term outcomes following curative‐intent resection of hepatocellular carcinoma

Diamantis I. Tsilimigras, J. Madison Hyer, Adrian Diaz, 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, Timothy M. Pawlik*

*Corresponding author for this work

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Introduction: The prognostic role of tumor burden score (TBS) relative to pre‐operative α ‐fetoprotein (AFP) levels among patients undergoing curative‐intent resection of HCC has not been examined. Methods: Patients who underwent curative‐intent resection of HCC between 2000 and 2017 were identified from a multi‐institutional database. The impact of TBS on overall survival (OS) and cumulative recurrence relative to serum AFP levels was assessed. Results: Among 898 patients, 233 (25.9%) patients had low TBS, 572 (63.7%) had medium TBS and 93 (10.4%) had high TBS. Both TBS (5‐year OS; low TBS: 76.9%, medium TBS: 60.9%, high TBS: 39.1%) and AFP (>400 ng/mL vs. <400 ng/mL: 48.5% vs. 66.1%) were strong predictors of outcomes (both p < 0.001). Lower TBS was associated with better OS among patients with both low (5‐year OS, low–medium TBS: 68.0% vs. high TBS: 47.7%, p < 0.001) and high AFP levels (5‐year OS, low–medium TBS: 53.7% vs. high TBS: not reached, p <0.001). Patients with low–medium TBS/high AFP had worse OS compared with individuals with low–medium TBS/low AFP (5‐year OS, 53.7% vs. 68.0%, p = 0.003). Similarly, patients with high TBS/high AFP had worse outcomes compared with patients with high TBS/low AFP (5‐year OS, not reached vs. 47.7%, p = 0.015). Patients with high TBS/low AFP and low TBS/high AFP had comparable outcomes (5‐year OS, 47.7% vs. 53.7%, p = 0.24). The positive predictive value of certain TBS groups relative to the risk of early recurrence and 5‐year mortality after HCC resection increased with higher AFP levels. Conclusion: Both TBS and serum AFP were important predictors of prognosis among patients with resectable HCC. Serum AFP and TBS had a synergistic impact on prognosis following HCC resection with higher serum AFP predicting worse outcomes among patients with HCC of a certain TBS class.

Original languageEnglish
Article number747
Pages (from-to)1-12
Number of pages12
Issue number4
Publication statusPublished - 2 Feb 2021
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • AFP
  • HCC
  • Resection
  • Surgery
  • Tumor burden


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