Publication Date
11-1-2024
Journal
Hepatology Communications
DOI
10.1097/HC9.0000000000000565
PMID
39495136
PMCID
PMC11537583
PubMedCentral® Posted Date
11-4-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Liver Neoplasms, Early Detection of Cancer, alpha-Fetoproteins, Carcinoma, Hepatocellular, Male, Female, Biomarkers, Tumor, Prothrombin, Ultrasonography, Hepatitis B, Chronic, Middle Aged, Protein Precursors, Adult, Liver Cirrhosis, Aged, Pragmatic Clinical Trials as Topic, Biomarkers, biomarker, GALAD, liver cancer, screening, ultrasound
Abstract
BACKGROUND: Professional guidelines recommend HCC screening in at-risk patients using semi-annual ultrasound with or without alpha-fetoprotein (AFP); however, this strategy has limited effectiveness due to low adherence and sensitivity. Increasing data support the potential role of blood-based biomarker panels, which could improve both aspects. The biomarker panel GALAD, comprised of sex, age, and 3 blood biomarkers (AFP, AFP-L3, and des-carboxy prothrombin des-carboxy prothrombin), has shown high sensitivity and specificity in biomarker phase II (case-control) and phase III (retrospective cohort) validation studies. However, prospective validation in a large phase IV biomarker clinical utility trial is necessary before its adoption in practice.
METHODS: The National Liver Cancer Screening Trial is an adaptive pragmatic randomized phase IV trial, which began enrollment in January 2024, comparing ultrasound-based versus biomarker-based screening in 5500 patients with chronic hepatitis B infection or cirrhosis from any etiology. Eligible patients are randomly assigned in a 1:1 ratio to semi-annual screening with ultrasound ± alpha-fetoprotein (arm A) or semi-annual screening with GALAD (arm B). Randomization is stratified by enrollment site, liver disease severity (per Child-Pugh class), liver disease etiology (viral, nonviral, and noncirrhotic HBV), and sex. Patients are being recruited from 15 sites (a mix of tertiary care academic referral centers, safety-net health systems, and large community health systems) over a 3-year period, and the primary endpoint, reduction in late-stage HCC, will be assessed at the end of year 5.5.
DISCUSSION: The results of this trial will inform the best strategy for HCC screening and early-stage detection in patients with chronic liver diseases. If GALAD shows superiority, HCC screening would primarily shift from an ultrasound-based strategy to the adoption of the biomarker panel.
TRIAL STATUS: The TRACER Study is actively enrolling.
Graphical Abstract
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Medical Sciences Commons, Nephrology Commons, Oncology Commons, Radiology Commons
Comments
TRIAL REGISTRATION: NCT06084234.
Supplementary Material