Recombinant human type-5 adenovirus (H101) combined with radiofrequency ablation versus traditional radiofrequency ablation for hepatocellular carcinoma ≤ 3 cm: a phase III randomized controlled trial

Background: Radiofrequency ablation (RFA) is standard for small hepatocellular carcinoma (HCC), yet recurrence remains common. This phase III trial compared RFA combined with recombinant human type-5 adenovirus (H101) versus traditional RFA in HCC ≤3 cm. Methods: This study prospectively collected data from patients between 2018 and 2021. This study included patients with a clinically or pathologically confirmed diagnosis of HCC characterized by a solitary tumor with a maximum diameter of ≤3 cm and excluded patients with distant metastasis. All patients were randomly allocated at a 1:1 ratio to the experimental group or the control group. The experimental group received RFA combined with H101, whereas the control group received traditional RFA. The primary endpoint was disease-free survival (DFS). The secondary endpoints included overall survival (OS) and safety. DFS and OS were evaluated in the intention-to-treat (ITT) population. Results: A total of 162 patients with small HCC were enrolled, with 81 patients randomized to each group, and ITT analysis was performed. The median follow-up durations for the RFA + H101 group and the RFA group were 36.47 months and 37.57 months, respectively. The 3-year OS rates for the RFA + H101 group and the RFA group were 93.00% and 92.90%, respectively, and the 3-year DFS rates were 54.00% and 41.20%, respectively. Comparisons of OS rates and RFS rates between the two groups revealed no significant differences (OS: P = 0.688; DFS: P = 0.090). The safety profiles of the two groups were both high, with no statistically significant differences observed. Conclusion: Compared with traditional RFA, the combination of RFA with H101 did not result in significant improvement in DFS rates among patients with small HCC. However, combination therapy has potential therapeutic advantages.