Postoperative adjuvant TACE combined with lenvatinib and immune checkpoint inhibitors for hepatocellular carcinoma with high recurrence risks: a multicenter retrospective study

BACKGROUND AND AIMS: The role of adjuvant therapy for hepatocellular carcinoma (HCC) patients with high recurrence risks after curative resection remains controversial. This study aimed to assess the efficacy and safety of postoperative adjuvant transarterial chemoembolization (TACE) combined with lenvatinib (LEN) and immune checkpoint inhibitors (ICIs) for these patients. METHODS: This multicenter, retrospective study included histologically confirmed HCC patients with high recurrence risks after curative resection during December 2015 and December 2023. Baseline differences were balanced between patients who received postoperative adjuvant TACE (TACE group) and TACE combined with LEN and ICIs (TACE-LEN-ICI group) by propensity score matching (PSM). The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS) and safety. RESULTS: Among 517 patients included in the analysis, 418 patients in TACE group and 99 patients in TACE-LEN-ICI group. After PSM, the TACE-LEN-ICI group had longer median RFS (HR = 0.69, 95% CI, 0.50–0.96, 34.0 vs. 18.8 months, P = 0.026) and OS (HR = 0.54, 95% CI 0.33–0.90, unreached vs. 81.6 months, P = 0.016) than TACE group. The 1-/2-/3-year RFS rates were 80.8%, 60.6%, and 42.5% in the TACE-LEN-ICI group and 60.1%, 46.9%, and 40.2% in the TACE group, respectively. The 1-/2-/5-year OS rates were 97.0%, 87.6%, and 54.4% in the TACE-LEN-ICI group and 85.9%, 70.7%, and 56.9% in the TACE group, respectively. Grade 3–4 adverse events occurred in 37 patients (37.4%) in TACE-LEN-ICI group, with no treatment-related death in both groups. CONCLUSIONS: Postoperative adjuvant TACE-LEN-ICI treatment appears safe and may offer survival benefits to HCC patients with high recurrence risks.