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Background & Aimsα-Fetoprotein (AFP) is widely used as a surveillance test for hepatocellular carcinoma (HCC) among patients with cirrhosis. Des-γ carboxy-prothrombin (DCP) and lectin-bound AFP (AFP-L3%) are potential surveillance tests for HCC. The aims of this study were to determine performance of DCP and AFP-L3% for the diagnosis of early HCC; whether they complement AFP; and what factors affect DCP, AFP-L3%, or AFP levels. MethodsWe conducted a large phase 2 biomarker case-control study in 7 academic medical centers in the United States. Controls were patients with compensated cirrhosis and cases were patients with HCC. AFP, DCP, and AFP-L3% levels were measured blinded to clinical data in a central reference laboratory. ResultsA total of 836 patients were enrolled: 417 (50%) were cirrhosis controls and 419 (50%) were HCC cases, of which 208 (49.6%) had early stage HCC (n = 77 very early, n = 131 early). AFP had the best area under the receiver operating characteristic curve (0.80, 95% confidence interval [CI]: 0.77–0.84), followed by DCP (0.72, 95% CI: 0.68–0.77) and AFP-L3% (0.66, 95% CI: 0.62–0.70) for early stage HCC. The optimal AFP cutoff value was 10.9 ng/mL leading to a sensitivity of 66%. When only those with very early HCC were evaluated, the area under the receiver operating characteristic curve for AFP was 0.78 (95% CI: 0.72–0.85) leading to a sensitivity of 65% at the same cutoff. ConclusionsAFP was more sensitive than DCP and AFP-L3% for the diagnosis of early and very early stage HCC at a new cutoff of 10.9 ng/mL. Abbreviations used in this paper: AFP, α-fetoprotein, AFP-L3%, lectin-bound α-fetoprotein, BDLC, Barcelona Clinic Liver Cancer staging system, CT, computerized tomography, DCP, des-γ carboxyprothrombin, EDRN, National Cancer Institute Early Detection Research Network, HCC, hepatocellular carcinoma, MRI, magnetic resonance imaging, US, ultrasound ⁎ University of Michigan, Ann Arbor, Michigan ‡ Fred Hutchinson Cancer Research Center, Seattle, Washington § Stanford University, Palo Alto, California ∥ Saint Louis University, St. Louis, Missouri ¶ Mayo Clinic, Rochester, Minnesota # University of Pennsylvania, Philadelphia, Pennsylvania ⁎⁎ Mayo Clinic, Jacksonville, Florida ‡‡ Mt. Sinai Liver Cancer Program, Mt. Sinai University, New York, New York §§ BCLC Group, Liver Unit, Institució Catalana de Recerca i Estudis Avançats, IDIBAPS, CIBERehd, Hospital Clínic Barcelona, Barcelona, Spain ∥∥ University of California, Los Angeles, Los Angeles, California ¶¶ National Cancer Institute, Bethesda, Maryland
Conflicts of interest The authors disclose no conflicts. Funding Supported by Early Detection Research Network of the National Cancer Institute (CA-084986), by grant DK064909 (to J.A.M), and by test kits provided by Wako Diagnostics and Eisai. PII: S0016-5085(09)00546-0 doi:10.1053/j.gastro.2009.04.005 © 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
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ABSTRACT
α-Fetoprotein, Des-γ Carboxyprothrombin, and Lectin-Bound α-Fetoprotein in Early Hepatocellular Carcinoma