High pretreatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma

Carolin Czauderna; Irene Schmidtmann; Sandra Koch; Lukas Pilz; Sophia Heinrich; Gerd Otto; Jens Mittler; Hauke Lang; Roman Kloeckner; Christoph Düber; Martin F Sprinzl; Marcus A Worns; Peter R Galle; Jens U Marquardt; Arndt Weinmann

doi:10.1177/2050640620972611

High pretreatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma

United European Gastroenterol J. 2021 Mar 11. doi: 10.1177/2050640620972611. Online ahead of print.

Authors

Carolin Czauderna^{1

2}, Irene Schmidtmann^{3

4}, Sandra Koch¹, Lukas Pilz¹, Sophia Heinrich¹, Gerd Otto⁴, Jens Mittler⁴, Hauke Lang⁴, Roman Kloeckner⁵, Christoph Düber⁵, Martin F Sprinzl¹, Marcus A Worns¹, Peter R Galle¹, Jens U Marquardt^{1

2}, Arndt Weinmann¹

Affiliations

¹ Department of Internal Medicine I, Johannes Gutenberg University, Mainz, Germany.
² Department of Medicine I, University Medical Centre SchleswigHolstein-Campus Lübeck, Lübeck, Germany.
³ Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Johannes Gutenberg University, Mainz, Germany.
⁴ Department of General, Visceral and Transplant Surgery, Johannes Gutenberg University, Mainz, Germany.
⁵ Department of Diagnostic and Interventional Radiology, Johannes Gutenberg University, Mainz, Germany.

PMID: 33709539
DOI: 10.1177/2050640620972611

Abstract

Background: Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein (AFP) is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static AFP values is limited and the clinical potential is a matter of ongoing scientific discussion.

Objective: We here evaluated the prognostic impact of pretreatment static and dynamic AFP variables on overall survival of hepatocellular carcinoma patients in a Western cohort.

Methods: Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg University Mainz between 1998 and 2014 and two available pretreatment AFP-values (AFP-slope) were retrospectively analysed. Clinicopathological baseline parameters, pretreatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan-Meier analyses and Cox regression models.

Results: High static and dynamic AFP variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child-Pugh B (p < 0.01) and C stage (p < 0.001), portal vein thrombosis (p < 0.001) and extrahepatic spread (p < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic AFP variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static AFP values.

Conclusion: Static and dynamic AFP variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.

Keywords: alpha-fetoprotein; biomarker; hepatocellular carcinoma; prognosis; survival.