Diamantis I Tsilimigras1, Dimitrios Moris1, J Madison Hyer1, Fabio Bagante1,2, Francesca Ratti3, Hugo P Marques4, Olivier Soubrane5, Vincent Lam6, George A Poultsides7, Irinel Popescu8, Sorin Alexandrescu8, Guillaume Martel9, Aklile Workneh9, Alfredo Guglielmi2, Tom Hugh10, Luca Aldrighetti3, Itaru Endo11, Timothy M Pawlik12,13. 1. Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA. 2. Department of Surgery, University of Verona, Verona, Italy. 3. Department of Surgery, Ospedale San Raffaele, Milan, Italy. 4. Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal. 5. Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France. 6. Department of Surgery, Westmead Hospital, Sydney, NSW, Australia. 7. Department of Surgery, Stanford University, Stanford, CA, USA. 8. Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania. 9. Department of Surgery, University of Ottawa, Ottawa, ON, Canada. 10. Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia. 11. Yokohama City University School of Medicine, Yokohama, Japan. 12. Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA. tim.pawlik@osumc.edu. 13. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University, Columbus, OH, USA. tim.pawlik@osumc.edu.
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.
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.