Practice changing RCT design and rationale: Abbreviated MRI plus AFP ultrasound plus AFP for HCC surveillance in cirrhosis (PREMIUM study).

Abdominal ultrasound every 6 months with or without serum alpha-fetoprotein (AFP) is recommended for hepatocellular carcinoma (HCC) screening in patients with cirrhosis. However, high-quality evidence demonstrating that this screening strategy reduces HCC-related mortality in cirrhosis is lacking. Dynamic contrast-enhanced abbreviated MRI (DCE aMRI) protocols for HCC screening have nearly identical performance to full multiphasic MRI (the gold standard for HCC diagnosis) and can be completed in under 15 min. PREMIUM is a multicentre randomised controlled trial comparing HCC screening by ultrasound+AFP every 6 months DCE aMRI+AFP every 6 months for up to 8 years among patients with cirrhosis. Sponsored by and executed within the Department of Veterans Affairs (VA), participant recruitment began in November 2023. Eligible participants are Veterans aged 18-75 years with cirrhosis, high HCC risk, Child-Turcotte-Pugh (CTP) score ≤9, model for end-stage liver disease (MELD) score ≤20, and no MRI contraindications or life-threatening comorbidities. The DCE aMRI protocol consists of T1-weighted axial pre-contrast and DCE sequences (arterial, portal, and 5-minute delayed) following administration of extracellular gadolinium-based contrast agent, plus a T2-weighted sequence between portal and delayed phases. PREMIUM aims to randomise 4,700 participants (2,350 in each arm), who will undergo per-protocol imaging and follow-up for up to 8 years. The primary outcome is HCC-related mortality. Secondary outcomes include HCC stage at diagnosis, receipt of potentially curative HCC treatment, and all-cause mortality. The study is powered to detect at least a 35% relative reduction in HCC-related mortality in the aMRI+AFP arm . the ultrasound+AFP arm. If PREMIUM demonstrates reduced HCC-related mortality in the aMRI+AFP arm, it could provide the necessary evidence to recommend aMRI+AFP for HCC screening in patients with cirrhosis (ClinicalTrials.gov identifier: NCT05486572). The PREMIUM Study is a registered clinical trial: NCT05486572.