Contrast-enhanced US with Perfluorobutane for Hepatocellular Carcinoma Surveillance: A Multicenter Diagnostic Trial (SCAN)

Abstract

Background US has served as a standard surveillance tool for hepatocellular carcinoma (HCC); however, the detection rate and false referral rate with this modality are suboptimal. Purpose To evaluate the added value of perfluorobutane-enhanced US when combined with conventional B-mode US as an HCC surveillance tool in participants with liver cirrhosis. Materials and Methods This prospective multi-institution diagnostic trial (https://ClinicalTrials.gov, NCT02188901) used an intraindividual comparison design in a single arm of study participants and was conducted at five referral hospitals. Eligible participants who had liver cirrhosis related to viral hepatitis and were undergoing US for HCC surveillance were enrolled from October 2014 to August 2016. Immediately after completion of B-mode US but before performance of perfluorobutane-enhanced US, operating radiologists entered the results of B-mode US. After completion of subsequent perfluorobutane-enhanced US (Kupffer phase with or without vascular-phase US), the radiologists recorded the results. The presence of HCC was confirmed either with pathologic analysis or radiologically by using dynamic contrast material-enhanced CT or gadoxetic acid-enhanced MRI. The primary end points were the detection rate of early-stage HCC (Barcelona Clinic Liver Cancer staging system stage 0 or A) and false referral rate. The primary end points were compared in a per-participant manner by using the McNemar test. Results A total of 524 participants (mean age, 54 years ± 9 [standard deviation]) were included. Of these, 493 (94.1%) had liver cirrhosis related to the hepatitis B virus. Ten HCCs were confirmed in eight participants. The detection rate of early-stage HCC was not significantly improved by adding perfluorobutane-enhanced US to conventional B-mode US (difference, 0.4% [95% confidence interval: -0.3%, 1.1%]; P = .16). The false referral rate was significantly reduced (difference, -3.2% [95% confidence interval: -5.0%, -1.4%]; P < .001). Conclusion The addition of perfluorobutane-enhanced US to conventional B-mode US reduced the false referral rate without a significant improvement in the detection rate of early-stage hepatocellular carcinoma for surveillance in a population in which the hepatitis B virus predominated.