Chemoembolization combined radiofrequency ablation vs. chemoembolization alone for treatment of beyond the Milan criteria viable hepatocellular carcinoma (CERFA): study protocol for a randomized controlled trial.

Background: Many previous studies evaluated a combination of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) for treating early hepatocellular carcinoma (HCC); however, studies evaluating combination therapy for beyond-the-Milan criteria HCC are scarce.

Methods: A total of 120 patients with beyond-the-Milan criteria HCC who have viable tumour after first TACE will be enrolled in this multi-institutional, parallel, pragmatic, randomized controlled trial. Patients with metastasis, vascular invasion, or a sum of tumour diameter > 8 cm will be excluded. Eligible patients will be randomly assigned to combination TACE and RFA therapy or TACE monotherapy groups. Patients in the combination therapy group will receive a second TACE and subsequent RFA at the viable tumour. Patients in the TACE monotherapy group will receive only second TACE. Patients in both groups will undergo magnetic resonance imaging 4-6 weeks after second TACE. The primary endpoint is 1-month tumour response, and secondary endpoints are progression-free survival, overall response rate, number of treatments until CR, overall survival, and change in liver function.

Discussion: Although TACE can be used to treat intermediate-stage HCC, it is difficult to achieve CR by first TACE in most intermediate-stage patients. Recent studies show a survival advantage of combination therapy over monotherapy. However, most studies evaluating combination therapy included patients with a single tumour sized < 5 cm, and no studies included patients with intermediate-stage but more advanced (i.e., beyond-the-Milan criteria) HCC. This study will evaluate the efficacy of combined TACE and RFA therapy for patients with advanced HCC within the intermediate stage.

Trial Registration: Clinical Research Information Service (CRiS) KCT0006483.