Although surgery is the preferred treatment for HCC, only 20%~30 patients can be resected due to the fact that most of the patients with liver cancer have chronic cirrhosis, or most of the patients have reached the middle or advanced stage at the time of diagnosis. In recent years, the development of local ablative treatment make some patients with HCC who are not suitable for hepatectomy have the chance of radical treatment. Local ablative treatment is a kind of therapeutic methods to target tumor with the guidance of medical imaging technology and directly kill tumor tissues by local physical or chemical methods [2]. RFA is a minimally invasive treatment of HCC ablation method commonly used. Alternating Current induced heat from the radio frequency electrode tip up to 60 ~ 100℃, When the tumor is exposed to this high temperature, clotting necrosis occurs almost immediately as an irreversible injury. Studies have shown that, in the absence of vascular, bile duct and adjacent organs invasion and distant metastasis, RFA has radical therapeutic effect for HCC patients whose liver function grade reaches Child-pugh A/B [15, 16]. However, tumor size has a significant impact on the efficacy of RFA. Livraghi T et al have shown that the postoperative necrosis rate of RFA is 60% for lesions with a maximum diameter of 3 ~ 5cm.The maximum tumor diameter > 5cm, the total tumor necrosis rate was only 24% [17], because it was difficult for the RFA range to completely cover the safe edge of the tumor when the tumor was large or had a special location. Some studies have also reported the long-term efficacy of RFA is very good which is used ≤ 2cm HCC. Histopathologically, areas with well differentiated in ≤ 2cm HCC are larger, with fewer satellite lesions and less portal vein invasion [18–20]. Multi-disciplinary treatment is highly regarded in recent years and treatment patterns, also contribute liver cancer diagnosis, entered the era of multidisciplinary multimodal coexist. The monotherapy method from the past, into a new model of joint application which including surgery, liver transplant, local ablation, TACE, radiotherapy, systemic chemotherapy, targeted therapy and so on.
The combination therapy of TACE and RFA has been gradually applied in the treatment of liver cancer. Jiang, F el at has shown that TACE-RFA can effectively control the growth of liver cancer lesions, reduce the level of tumor-related serum markers, and inhibit tumor cell activity [21], but Kim JW el at. have reported conflicting results which shown that the similar effective between TACE-RFA and RFA[22]. However, in this meta-analysis, we showed that the TACE-RFA group was associated with a higher 3-year or 5- year OS rate than the RFA group, and they have the significant difference. This is consistent with the outcomes reported in a recent meta-analysis [8], although the 1-year OS rate has no significant difference. This was consistent with the study by R. Iezzi, M et al [23]. The reason of high OS rate after the treatment TACE-RFA as follows: Firstly, during the combined treatment, iodide precipitates around the lesion. Therefore, it can not only be used as a marker of RFA that making it easier for the operator to identify the ablation area, but also act as a thermal conduction medium to improve the ablation efficiency and keep the surrounding HCC microenvironment in a static state. By improving the ablation effect, tumor recurrence can be reduced [24]. Secondly, TACE can reduced heat loss during RFA by blocking blood flow into the tumor [25]. Thirdly, Chemotherapy-Cancer drugs increase the effect of high body temperature on cancer cells. Finally, TACE can further treat micro-lesions that cannot be detected by naked eye or imagings, thus improving the OS rate of patients.
Tumor recurrence and progression are the major risk factors affecting the prognosis of HCC patients [26]. To the best of our knowledge, RFA is not a suitable treatment for greater nodular or multiple nodular tumors. Moreover, Nakashima O et al found early recurrence and multiple recurrent nodules are related to portal vein tumor thrombus [27]. TACE-RFA can effectively induce those nodular necrosis and improve the tumor necrosis rate, and chemotherapy-cancer drugs also has better curative effect on portal vein tumor thrombus. Our meta-analysis also shows that the 3- and 5-year RFS rate is higher in the TACE-RFA group than RFA group. And the tumor progression is also lower in the TACE-RFA group than RFA group.
Major complications of RFA include gastrointestinal perforation, biliary stenosis, bile leakage, tumor seeding, abscess formation, septicemia, peritonitis, cardiac arrest, pulmonary embolism, and left pneumothorax and so on[17]. The most common complications to TACE treatment mainly characterized by acute hepatic impairment, acute renal impairment, gastrointestinal bleeding, cholecystitis and gallbladder perforation, embolization agent ectopic embolization and so on. Liver failure after TACE is the main limitation of survival benefit. In a previous study, it happened to more than 50 percent of patients [28]. However, major complications after TACE-RFA are uncommon. In previous studies, TACE-RFA has been shown to be safe, with the incidence of major complications ranging from 0 to 2.2% [29, 30]. Our meta-analysis showed that the TACE-RFA group was associated with a lower incidence rate of complications than the RFA group, but it has no significant difference was shown by this study. We hypothesized that the combination of TACE and RFA might result in the simultaneous occurrence of two treatment-related complications. Finally, heterogeneity in the occurrence of major complications (I2 = 67%) may have resulted from of the use of different definitions among major complications.
The limitations of meta-analysis include the following: the studies are all from Asian populations, the number of included studies was limited, and the differences about Child-Pugh class, tumor size, number of tumors, tumor stage and so on was used. These factors may affect the reliability of the conclusion.