Efficacy and safety of adjuvant transarterial chemoembolization in high-risk HCC after curative hepatectomy: a phase III RCT protocol.

INTRODUCTION

Hepatocellular carcinoma (HCC) remains associated with a high risk of recurrence, with 5-year recurrence rates approaching 70% after curative hepatectomy. The Chinese Liver Cancer Staging guideline strongly recommend transarterial chemoembolization (TACE) as an adjuvant therapy to reduce postoperative recurrence and improve overall survival. However, its clinical benefit remains controversial, as guidelines from other regions do not support routine use of adjuvant TACE. This discrepancy may reflect the possibility that adjuvant TACE primarily facilitates detection of intrahepatic residual lesions through digital subtraction angiography (DSA), rather than conferring direct therapeutic benefit from embolic or chemotherapeutic agents.

METHODS AND ANALYSIS: This multicenter, phase III randomized controlled trial will enroll 442 eligible participants, who will be randomly assigned in a 1:1 ratio to either an adjuvant TACE group or an intensive follow-up group. The primary endpoint of this study is to investigate whether adjuvant TACE could improve recurrence-free survival (RFS) in high-risk HCC patients following curative hepatectomy. The key secondary endpoints include the safety and tolerability of adjuvant TACE, as well as the effects of adjuvant TACE versus intensive follow-up on overall survival, median RFS, and time to tumor recurrence. This trial may addresses the critical clinical controversy regarding adjuvant TACE by excluding patients with residual tumor staining on DSA, to ensure genuine curative resection. The results will deliver high-quality evidence to clarify the efficacy and safety of adjuvant TACE, and standardize postoperative adjuvant strategies.