Comparative evaluation of TACE-RFA versus monotherapies on a background of systemic therapy for recurrent hepatocellular carcinoma: a propensity score-matched analysis.

Background: The optimal locoregional treatment for recurrent hepatocellular carcinoma (rHCC) in the era of potent systemic therapy remains undefined. This study aimed to compare the efficacy, safety, and resource consumption of transarterial chemoembolization combined with radiofrequency ablation (TACE-RFA) versus TACE or RFA monotherapy, specifically when administered on a uniform background of systemic therapy (Lenvatinib plus PD-1 inhibitors). Methods: We retrospectively reviewed 243 patients with rHCC who met strict eligibility criteria (tumor size 3.0-7.0 cm, ≤3 recurrent nodules, and preserved liver function, corresponding to Barcelona Clinic Liver Cancer (BCLC) A/B and China Liver Cancer (CNLC) Ia-IIa stages. Crucially, all included patients uniformly received standardized peri-procedural systemic therapy (Lenvatinib and Tislelizumab). Based on the actual locoregional strategies, the cohort was divided into TACE-RFA (n=56), TACE alone (n=114), or RFA alone (n=73) groups. To mitigate selection bias, 1:1 propensity score matching (PSM) was employed, generating two matched cohorts: Combination vs. TACE alone (54 pairs) and Combination vs. RFA alone (54 pairs). Survival outcomes, post-procedural pain, hospital stay, and costs were evaluated. Results: After PSM, baseline characteristics were well-balanced. The median progression-free survival (PFS) in the combination group was 21.4 months, significantly superior to the matched TACE monotherapy cohort (13.5 months, P < 0.001) and the independently matched RFA monotherapy cohort (10.4 months, P < 0.001). Overall survival (OS) showed no significant differences among the groups (median OS 48.9-50.5 months, all P > 0.05), likely because the uniform administration of potent systemic therapy drastically prolonged the baseline survival for all patients, thereby diluting the OS advantage of local control. Safety profiles were comparable across all modalities (P > 0.05). Predictably, combination therapy incurred longer median hospital stays and higher total costs compared to monotherapies (all P < 0.001). Conclusion: For rHCC patients receiving concurrent Lenvatinib and PD-1 inhibitors, sequential TACE-RFA therapy provides a profound and independent progression-free survival benefit over locoregional monotherapies without increasing patient discomfort. The superior local tumor control justifies the anticipated initial increases in perioperative resource consumption.