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Abstract Details
The Performance of AFP, AFP-3, DCP as Biomarkers for Detection of Hepatocellular Carcinoma (HCC). A Phase 3 Biomarker Study in the United States
Clin Gastroenterol Hepatol. 2022 Feb 3;S1542-3565(22)00106-9. doi: 10.1016/j.cgh.2022.01.047.Online ahead of print.
Department of Data Science, Dana-Farber Cancer Institute (Boston, MA).
Section of Gastroenterology and Hepatology, Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX; Houston VA Health Services Research and Development Service Center of Excellence (Houston, TX), Section of Health Services Research, Michael E. DeBakey VA Medical Center (Houston, TX) and Baylor College of Medicine, (Houston, TX).
Section of Gastroenterology and Hepatology, Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX; Houston VA Health Services Research and Development Service Center of Excellence (Houston, TX), Section of Health Services Research, Michael E. DeBakey VA Medical Center (Houston, TX) and Baylor College of Medicine, (Houston, TX). Electronic address: hasheme@bcm.edu.
Abstract
Background: AFP, AFP L-3 and DCP in combination or in GALAD were tested for HCC surveillance in retrospective cohort and case-control studies. However, there is a paucity of prospective data and no phase 3 biomarker studies from North American populations.
Methods: We conducted a prospective-specimen collection, retrospective-blinded-evaluation (PRoBE) cohort study in patients with cirrhosis enrolled in a 6-monthly surveillance with liver imaging and AFP. Blood samples were prospectively collected every 6 months and analyzed in a retrospective blinded fashion. True positive rate (TPR) and false positive rate (FPR) for any or early HCC were calculated within 6, 12 and 24 months of HCC diagnosis based on published thresholds for biomarkers individually, in combination and in GALAD and HES scores. We calculated the area under the receiver operating curve (AUROC) and estimated TPR based on an optimal threshold at a fixed FPR of 10%.
Results: The analysis was conducted in a cohort of 534 patients; 50 developed HCC (68% early) and 484 controls with negative imaging. GALAD had the highest TPR (63.6, 73.8, 71.4% for all HCC, and 53.8, 63.3, 61.8 % for early HCC within 6, 12 and 24 months, respectively) but FPR of 21.5-22.9%. However, there were no differences in AUROC among GALAD, HES, AFP-3 or DCP. At a fixed 10% FPR, TPR for GALAD dropped (42.4, 45.2, 46.9%) and was not different from HES (36.4, 40.5, 40.8%) or AFP-3 alone (39.4, 45.2, 44.9%).
Conclusions: In a prospective cohort phase 3 biomarker study, GALAD was associated with a considerable improvement in sensitivity for HCC detection but an increase in false positive results. GALAD performance was modest and not different from AFP-3 alone or HES.