Transarterial Chemoembolization Plus Thermal Ablation in Unresectable Hepatocellular Carcinoma

Importance: Transarterial chemoembolization (TACE) is the standard of care for liver-confined hepatocellular carcinoma (HCC) that is not amenable to curative treatment; however, TACE has demonstrated unsatisfactory survival benefits. Objective: To evaluate whether combining TACE with subsequent thermal ablation improves clinical outcomes compared with TACE alone in patients with liver-confined unresectable HCC. Design, Setting, and Participants: The open-label, phase 3 TORCH randomized clinical trial was conducted from May 2015 to August 2024 at 2 tertiary medical centers in China. Patients with Barcelona Clinic Liver Cancer stage B HCC were enrolled. The data cutoff was October 31, 2025. Interventions: Patients were randomly assigned (1:1) to receive either TACE combined with subsequent selective radiofrequency ablation (TACE-ablation) or TACE alone. Main Outcomes and Measures: The primary end point was progression-free survival (PFS), assessed per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Secondary end points included overall survival (OS), treatment response and PFS per modified RECIST, untreatable PFS, and safety. Results: Among 241 patients included in the intention-to-treat population, 121 received TACE-ablation (median [IQR] age, 59.0 [51.0-66.0] years; 108 [89.3%] male), and 120 received TACE alone (mean [IQR] age, 58.0 [50.0-64.0]; 106 [88.3] male). The number of patients with 6-and-12 tumor burden scores of lower than 6, 6 to 12, and more than 12 points were 34 (28.1%), 79 (65.3%), and 8 (6.6%) in the TACE-ablation group and 31 (25.8%), 76 (63.3%), and 13 (10.8%) in the TACE alone group, respectively. At the data cutoff, the median PFS per RECIST, version 1.1, was 17.7 months (95% CI, 11.4-23.1 months) in the TACE-ablation group vs 7.3 months (95% CI, 6.4-10.4 months) in the TACE alone group (hazard ratio [HR], 0.47; 95% CI, 0.34-0.65; P < .001). TACE-ablation also resulted in statistically significant prolonged untreatable PFS compared with TACE (35.1 months vs 12.3 months; HR, 0.40; 95% CI, 0.27-0.58; P < .001). Median OS was 88.6 months (95% CI, 43.1 months to not estimable) with TACE-ablation and 35.1 months (95% CI, 25.4-45.5 months) with TACE alone (HR, 0.50; 95% CI, 0.34-0.73; P < .001). Clinically meaningful improvements in both PFS and OS were observed in patients with low to moderate tumor burden scores (≤6 and 6-12 points). Grade 3 and 4 treatment-related adverse events occurred in 23 patients (23.2%) in the TACE-ablation group and 24 (18.3%) in the TACE alone group. Conclusions and Relevance: In this phase 3 randomized clinical trial, TACE combined with subsequent thermal ablation demonstrated superior survival outcomes than TACE alone in patients with liver-confined unresectable HCC. Sequential TACE-ablation could serve as a feasible treatment option for such patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02435953.