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

BACKGROUND AND AIMS: The role of adjuvant transarterial chemoembolization (TACE) for HCC following curative resection remains controversial. We aimed to determine the effectiveness of postoperative adjuvant TACE in patients with HCC​​​​​. APPROACH AND RESULTS: In this randomized phase 3 trial, histologically confirmed patients with HCC (American Joint Committee on Cancer 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 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 2 groups from the ITT population (median, both unreached; HR, 0.88; 95% CI: 0.62-1.24; p =0.468). The RFS rates at 1, 3, 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 overall survival was comparable between the TACE group and the observation group in the ITT population (median, both unreached, HR, 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 overall survival in patients with American Joint Committee on Cancer TNM stage I or II HCC.