National Liver Cancer Screening Trial (TRACER) study protocol.

Area of Science:

• Hepatology
• Oncology
• Biomarker Discovery

Background:

• Current hepatocellular carcinoma (HCC) screening guidelines recommend ultrasound with or without alpha-fetoprotein (AFP), but face challenges with adherence and sensitivity.
• Blood-based biomarker panels, such as the GALAD score (including sex, age, AFP, AFP-L3, and des-carboxy prothrombin), show promise for improved HCC detection.
• Prospective validation of the GALAD panel in a large clinical utility trial is needed.

Purpose of the Study:

• To compare the effectiveness of ultrasound-based screening versus biomarker-based screening (GALAD) for early HCC detection.
• To evaluate the potential of the GALAD biomarker panel to improve HCC screening adherence and sensitivity.
• To inform clinical practice regarding optimal HCC screening strategies in patients with chronic liver diseases.

Main Methods:

• An adaptive pragmatic randomized phase IV trial (National Liver Cancer Screening Trial) enrolling 5500 patients with chronic hepatitis B or cirrhosis.
• Patients are randomized 1:1 to semi-annual screening with ultrasound ± AFP (arm A) or semi-annual screening with GALAD (arm B).
• Stratification by enrollment site, liver disease severity, etiology, and sex; primary endpoint is reduction in late-stage HCC.

Main Results:

• This section is not yet available as the trial is actively enrolling.

Conclusions:

• The trial's results will guide the optimal strategy for HCC screening and early detection.
• If the GALAD panel demonstrates superiority, it could lead to a shift from ultrasound-based screening to biomarker-based approaches for HCC.