Controversy erupted at the HCC Evidence-based Practice Debates at WCIO 2016 regarding combination therapy for HCC. Panelist, expert and author Karen Brown, MD from Memorial Sloan-Kettering Cancer Center responds:
Combining embolization with ablation has several advantages, whether for small tumors or those larger than 3cm. Smaller primary liver tumors can be difficult to target with either CT or US within the background of cirrhosis, present in the majority of patients.Although this can potentially be overcome using either CEUS or fusion imaging not all practitioners are experienced with these techniques.Accurate targeting is critical for achieving complete ablation.Embolizing the tumor first allows for very accurate targeting since the tumor will be stained with either lipiodol if TACE is used, which increases conspicuity on both US and CT, or with contrast when TAE or DEB-TACE is performed because the embolization agent traps contrast within the tumor when intra-tumoral stasis is achieved. In the case of tumors larger than 3cm, the risk of recurrence is known to be higher when treated with ablation alone.Embolizing the tumor first enhances the ablation zone by multiple mechanisms.Flow within the regional vessels is reduced or eliminated, so there is less perfusion-mediated cooling to overcome.Around the central zone of lethal thermal coagulation a is large zone of hyperthermia in which tissue has been heated between 40-50°C. Hyperthermia and doxorubicin act synergistically to increase tumor cell death within the hyperthermic zone. If part of the tumor is undertreated by the embolization, for example if a feeder has been missed, this is quite clear on a CT obtained within 24 hours that will demonstrate a “defect” in uptake of contrast or lipiodol in the undertreated region.This area can be specifically targeted during the subsequent ablation.
Many studies have been done exploring the outcome of combining TACE plus ablation, including two RCTs; a small trial from 20101 in which the rate of local PFS was significantly better in the combined treatment group and a larger study2 from 2013 in which TACE-RFA was found superior to RFA alone in patients with solitary HCC < 7.0cm in diameter. Similar findings were reported in a large retrospective study by Kim et al, who also found treatment allocation (TACE vs TACE +ablation) to be a significant predictor of survival, favoring the combined treatment group3. A retrospective study of patients with tumor burden meeting Milan criteria found no difference is survival whether treatment was surgical resection or TACE plus RFA4. After finding no significant difference in overall survival between patients treated with TAE plus ablation in solitary tumors up to 7cm in size compared to surgical resection in an exploratory retrospective review in 20055 this became a common method of treatment in our group. We published a follow-up study (median follow-up 11 years) with similar findings in 20136.Median OS was 66 months in the resection group and 58 months in the TAE-ablation group (p =0.39).
I certainly consider it “best practice” to combine hepatic transarterial embolization with ablation for HCC >3.0cm in diameter knowing that I am much less likely to have to come back and treat a local recurrence. The fact that not just the PFS but also the OS has been shown to be better with combined therapy also informs my decision. This evidence should be seriously considered by those treating patients with HCC.
1.Morimoto M, Numata K, Kondou M, et al: Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer 116:5452-60, 2010
2.Peng ZW, Zhang YJ, Chen MS, et al: Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol 31:426-32, 2013
3.Kim JH, Won HJ, Shin YM, et al: Medium-sized (3.1-5.0 cm) hepatocellular carcinoma: transarterial chemoembolization plus radiofrequency ablation versus radiofrequency ablation alone. Ann Surg Oncol 18:1624-9, 2011
4.Kagawa T, Koizumi J, Kojima S, et al: Transcatheter arterial chemoembolization plus radiofrequency ablation therapy for early stage hepatocellular carcinoma: comparison with surgical resection. Cancer 116:3638-44, 2010
5.Maluccio M, Covey AM, Gandhi R, et al: Comparison of survival rates after bland arterial embolization and ablation versus surgical resection for treating solitary hepatocellular carcinoma up to 7 cm. J Vasc Interv Radiol 16:955-61, 2005
6.Elnekave E: Long-Term Outcomes Comparing Surgery to Embolization-Ablation for Treatment of Solitary HCC <7 cm. Annals of surgical oncology:1-6, 2013