Highlight
The phase 3 TORCH randomized clinical trial evaluated the efficacy of combining transarterial chemoembolization (TACE) with selective radiofrequency ablation (thermal ablation) in patients with unresectable hepatocellular carcinoma (HCC). The study demonstrated a substantial improvement in progression-free survival (PFS) and overall survival (OS) when TACE was followed by thermal ablation compared to TACE alone. Safety profiles were comparable with manageable adverse events. These findings suggest that sequential TACE-ablation offers a superior treatment strategy for liver-confined unresectable HCC.
Study Background and Disease Burden
Hepatocellular carcinoma (HCC) ranks as one of the leading causes of cancer-related morbidity and mortality worldwide, especially in regions with high prevalence of chronic liver disease. For patients with liver-confined disease who are not candidates for curative therapies such as surgical resection or liver transplantation, transarterial chemoembolization (TACE) remains the standard of care. However, TACE alone often results in suboptimal survival outcomes due to incomplete tumor eradication and high recurrence rates.
Efforts to enhance local tumor control and prolong survival have led to interest in combining TACE with thermal ablation techniques like radiofrequency ablation (RFA). Thermal ablation aims to destroy residual viable tumor cells after TACE, potentially improving treatment efficacy. Yet, robust phase 3 clinical trial evidence supporting this combined approach had been lacking prior to the TORCH trial.
Study Design
The TORCH trial was a prospective, open-label, phase 3 randomized clinical trial conducted at two tertiary medical centers in China from May 2015 to August 2024, enrolling 241 patients with Barcelona Clinic Liver Cancer (BCLC) stage B unresectable HCC confined to the liver. Patients were randomized 1:1 to receive either TACE followed by selective radiofrequency ablation (TACE-ablation group) or TACE alone (control group). Key eligibility required liver-confined tumors not amenable to curative resection or transplantation, with functional liver reserve permitting interventional therapy.
The primary endpoint was progression-free survival (PFS) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Secondary endpoints included overall survival (OS), treatment response and PFS by modified RECIST criteria, untreatable progression-free survival (untreatable PFS), and safety evaluation based on grade 3-4 treatment-related adverse events.
Key Findings
Baseline Characteristics
The intention-to-treat population included 241 patients: 121 in the TACE-ablation group (median age 59 years; 89.3% male) and 120 in the TACE-alone group (median age 58 years; 88.3% male). Tumor burden, assessed by the 6-and-12 tumor burden score, was comparable between groups with the majority classified as low to intermediate burden.
Progression-Free Survival
The primary endpoint, median PFS per RECIST 1.1 criteria, was significantly longer in the TACE-ablation group at 17.7 months (95% CI, 11.4-23.1) compared to 7.3 months (95% CI, 6.4-10.4) in the TACE-alone group. The hazard ratio (HR) for progression or death was 0.47 (95% CI, 0.34-0.65; P < .001), indicating a 53% reduction in risk with combination therapy.
Untreatable PFS—time until progression no longer amenable to further treatment—was also markedly prolonged with TACE-ablation (median 35.1 vs 12.3 months; HR 0.40; 95% CI, 0.27-0.58; P < .001), underscoring delayed development of refractory disease.
Overall Survival
Survival analysis demonstrated a median OS of 88.6 months (95% CI, 43.1 months to not estimable) in the TACE-ablation group, significantly exceeding the 35.1 months (95% CI, 25.4-45.5) observed in patients receiving TACE alone (HR 0.50; 95% CI, 0.34-0.73; P < .001). This more than doubling of median survival establishes a clinically meaningful benefit from the combined approach.
Subgroup Analysis
Patients with low to moderate tumor burden scores (≤6 and 6-12 points) derived the most pronounced improvements in both PFS and OS, suggesting the combination therapy’s efficacy may be influenced by tumor burden.
Treatment Safety
Grade 3 and 4 treatment-related adverse events occurred in 23.2% of patients in the TACE-ablation group versus 18.3% in the TACE-alone group. Despite a slight increase in adverse events following combination therapy, the differences were modest and manageable, with no unexpected safety signals. These findings support the tolerability of sequential TACE followed by selective radiofrequency ablation.
Expert Commentary
The TORCH trial provides compelling level 1 evidence confirming the advantage of combining TACE with thermal ablation over TACE alone in unresectable, liver-confined HCC. The more than twofold median OS increase is particularly notable given the historically limited survival gains with TACE monotherapy. This study rigorously addresses a prior gap in evidence and reinforces a treatment paradigm that integrates locoregional therapies to optimize tumor control.
While these findings are highly promising, certain considerations remain. The trial was conducted in two centers in China, a region with high HCC incidence and predominant hepatitis B-related etiology, which may affect generalizability to other populations. Furthermore, the open-label design, although pragmatic, could introduce assessment bias despite objective radiologic endpoints.
From a mechanistic standpoint, TACE reduces tumor bulk and induces ischemic necrosis, creating a window of opportunity for subsequent thermal ablation to eradicate residual viable tumor cells and micrometastases. This sequential approach leverages complementary modes of action to improve local disease control.
Conclusion
The phase 3 TORCH trial demonstrates that sequential therapy comprising transarterial chemoembolization followed by selective radiofrequency ablation significantly improves progression-free and overall survival compared with TACE alone in patients with liver-confined unresectable hepatocellular carcinoma. This combination treatment exhibits an acceptable safety profile and confers clinically meaningful benefits, especially among patients with low to intermediate tumor burden.
These findings advocate for incorporation of selective thermal ablation after TACE in appropriate patients, potentially redefining standard care for intermediate-stage HCC. Further research should explore broad applicability across diverse populations and refine patient selection criteria to maximize therapeutic gains.
Funding and Clinical Trial Registration
The TORCH trial was funded by institutional research support at participating Chinese tertiary centers. The trial is registered under ClinicalTrials.gov Identifier: NCT02435953.
References
- Lyu N, Yi JZ, Wu XT, et al. Transarterial Chemoembolization Plus Thermal Ablation in Unresectable Hepatocellular Carcinoma: The Phase 3 TORCH Randomized Clinical Trial. JAMA Oncol. 2026 Jul 30. PMID: 42530948.
- Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37(2):429-42.
- Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301-1314.
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182-236.
