Adjuvant transarterial chemoembolization for hepatocellular carcinoma following curative resection: A randomized, open-label, phase 3 trial

Background & Aims: The role of adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) following curative resection remains controversial. We aimed to determine the effectiveness of postoperative adjuvant TACE in HCC patients. Approach & Results: In this randomized phase 3 trial, histologically confirmed HCC patients (AJCC TNM stage I and II) were randomly assigned (1:1) to adjuvant TACE or observation groups. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat (ITT) population. The secondary endpoints included overall survival (OS) and safety. A total of 332 patients (ITT population) were randomly assigned to the TACE group (n=166) or the observation group (n=166) between March 2014 and June 2021. The RFS was comparable between the two groups from the ITT population (median, both unreached; hazard ratio, 0.88; 95% CI, 0.62–1.24; p =0.468). The RFS rates at 1 year, 3 years, and 5 years were 87.3% (95% CI, 81.2-91.5), 70.7% (95% CI, 63.0-77.0), and 60.6% (95% CI, 51.9-68.3) in the adjuvant TACE group and 84.8% (95% CI, 78.3-89.5), 69.3% (95% CI, 61.6-75.8), and 58.1% (95% CI, 49.5-65.8) in the observation group, respectively. The OS was comparable between the TACE group and the observation group in the ITT population (median, both unreached, hazard ratio, 1.06; 95% CI, 0.63–1.76; p =0.838). There was no grade ≥ 3 adverse event or treatment-related death in either group. Conclusions: Postoperative adjuvant TACE was not associated with prolonged RFS or OS in AJCC TNM stage I or II HCC patients.