Colorectal cancer is one of the most common malignant tumors, ranking the 3rd most common malignant tumor in the world and the 2nd most common malignant tumor in the digestive system in China. Colorectal liver metastasis (CRLM) is a difficult problem in the treatment of colorectal cancer and is also the leading cause of death. The literature reports that 15%-25% of colorectal cancer patients have CRLM (simultaneous liver metastasis) at the time of definite diagnosis, and another 15%-40% have CRLM (heterochronic liver metastasis) after treatment of the primary tumor; the median survival of untreated CRLM patients is only 6.9 months. Surgical resection is the most effective means of eradicating CRLM, with a 5-year survival rate of 23% to 58%. Previous data suggest that less than 20% of patients with CRLM are able to obtain radical resection; and a recent study showed that of 42,766 patients admitted to the United States between 1991 and 2006, only 2,121 (5%) were treated with surgical resection. This implies, in part, that the use of surgical resection in the treatment of CRLM is becoming increasingly cautious; for most patients with CRLM, there is a lack of more effective treatment options supported by evidence other than chemotherapy. Radiofrequency ablation (RFA) is a common means of local treatment for liver tumors, with the advantages of definite efficacy, high safety, low trauma, and repeatable treatment, and can be the treatment of choice for early-stage hepatocellular carcinoma. In the past decade or so, RFA has been increasingly used in the treatment of CRLM with richer experience, significantly improved equipment, more and more certain efficacy and more prominent advantages, and has achieved promising preliminary results. In this paper, we would like to discuss the current situation of RFA treatment for CRLM and its position in the comprehensive treatment of CRLM as follows. I. Principle and characteristics of radiofrequency ablation therapy The basic principle of treating liver tumor is to use radiofrequency current to make the positive and negative ions in cancer tissue vibrate at high speed and generate heat by friction, and the local temperature is as high as 105-115℃, which leads to a series of changes such as biofilm structure and function of tumor cells, cell dehydration, organelle destruction and coagulative necrosis of tissues; in addition, it is also able to cause microvascular embolism in the area around the ablation foci through In addition, it can also enhance the ablation effect through the mechanisms of microvascular embolism, tissue hypoxia, activation of blast cells and alteration of cytokine profile in the area around the ablation focus. Compared with surgical treatment, RFA has two characteristics in treating liver tumors: firstly, local removal of cancer foci can minimize the innocent loss of normal liver tissues; secondly, ablation of multiple foci can be accomplished more easily through multi-site ablation; thirdly, the ablated tumor tissues remain in the liver and some components are absorbed into the blood, which can be used as endogenous tumor antigens. This can further stimulate or amplify the anti-tumor immune response of the body on the basis of the original tumor immunity. Preliminary studies have shown that dendritic cell antigen-presenting function, tumor-specific T lymphocyte activity, NK cell activity, and hepatic blast cell activity are significantly enhanced after RFA treatment, and the above responses have a significant tumor suppressive effect [15-17]. Second, the current status of RFA for CRLM In 1998, Rossi et al. reported the application of percutaneous RFA for 55 patients with liver tumors, 6 of whom were patients with CRLM, which was probably the initial literature on the application of RFA for CRLM In 1998, Elias et al. reported that RFA could be combined with surgical resection to expand the indications for surgical resection of CRLM. Since then, the use of RFA in the comprehensive treatment of CRLM has been increasing. Although RFA for CRLM started no later than RFA for hepatocellular carcinoma, it is far behind RFA for hepatocellular carcinoma in terms of the popularity of its current development, the breadth and depth of research, and its efficacy. Several randomized controlled studies have shown that the efficacy of RFA for early-stage hepatocellular carcinoma is comparable to that of surgical resection, and the US NCCN guidelines have listed RFA, together with surgical resection and liver transplantation, as the three curative means for early-stage hepatocellular carcinoma. In contrast, RFA is mainly used for the treatment of inoperable CLM or as an adjuvant treatment option during surgical resection in the comprehensive treatment of CLM, and there are no randomized controlled studies comparing the efficacy with other treatment modalities. The main reasons why RFA for CRLM is not yet widely practiced include the following: first, colorectal cancer is a more purely “surgical disease”, and RFA is mostly performed by non-surgeons who are less likely to treat such patients, and it is far from common for surgeons to perform RFA, making it difficult to study the relative separation of patients and means. Secondly, for a long time, especially in the early stage of RFA, the indications of RFA for liver tumors were limited to single small lesions, while the main characteristics of CRLM were multiple lesions, which affected the development of RFA for CRLM to a considerable extent; thirdly, because the modern concepts of repeated application of RFA and ablation boundaries were not yet popular, the advantages of RFA were not fully explored. The advantages of RFA have not yet been fully exploited, which is especially obvious in the treatment of CRLM. Summarizing the recent literature, it can be seen that the application of RFA for the treatment of CRLM has the following two main aspects. First, treatment of CRLM that cannot be surgically resected, including cases where the tumor is adjacent to large intrahepatic vessels, insufficient volume of residual liver after surgery, many systemic comorbidities, combined with extrahepatic metastases or refusal of surgical resection. Second, surgical resection combined with RFA for CRLM. For multiple CRLM lesions involving both left and right hemispheres, the larger lesions can be surgically resected while RFA is applied to treat the smaller lesions. For larger CRLM, RFA can also play the role of a surgical instrument to assist in hepatectomy. Dedicated RFA electrodes, represented by Habib, can ablate the surgical preincision line into a coagulative necrotic zone, which both reduces intraoperative bleeding and provides an ideal tumor-free margin. Surgical resection combined with RFA can reduce surgical risk and avoid excessive resection of normal liver, while ensuring surgical efficacy, and therefore is increasingly used clinically. mayo et al. analyzed the treatment modalities of 2121 patients with CRLM between 1991 and 2006, and found that RFA-assisted hepatic wedge resection was gradually increasing, while simple liver resection, especially major hepatectomy (hemihepatectomy and trilobar hepatectomy) gradually decreased. Comparison of the efficacy of RFA and surgical resection for CRLM data show that the 5-year survival rate of patients with CRLM is 23%-58% after surgical resection and up to 51%-58% after combined chemotherapy. The American Society of Clinical Oncology searched and analyzed 73 reviews and papers on RFA CRLM treatment published between 1996 and 2007, and the results showed that the 5-year survival rate of RFA CRLM treatment ranged from 14% to 55%, the local recurrence rate ranged from 3.6% to 60%, and the major complications ranged from 6% to 9%; the main reasons for the large variation in the results of the studies were: different inclusion criteria (including CRLM number, diameter, choice of chemotherapy timing and the presence of extrahepatic metastases), a large time span in the literature, and different RFA pathways (percutaneous, laparoscopic and open pathways). In recent years, with the accumulation of clinical experience, technical improvements, and upgrades in radiofrequency ablation instrumentation, RFA for inoperable CRLM has achieved a 5-year survival rate similar to that of surgically resected CRLM. Gillams et al. retrospectively summarized 40 patients with a mean diameter of 2.3 cm (range 0.8-4.0 cm) with solitary inoperable CRLM treated with percutaneous RFA treatment with a mean follow-up of 38 months. The results showed a median survival time of 63 months from the diagnosis of CRLM, with 1-, 3-, and 5-year survival rates of 100%, 88%, and 54%, respectively, and a median survival time of 59 months from the time of RFA treatment, with 1-, 3-, and 5-year survival rates of 97%, 84%, and 40%, respectively.Berber et al [5] retrospectively compared surgical resection with laparoscopic RFA The long-term outcome of patients with solitary CRLM treated with surgical resection in 90 cases and laparoscopic RFA in 68 cases (25 cases with inoperable resection, 24 cases with many comorbidities, 10 cases with extrahepatic metastases, and 9 cases who refused surgery) showed that the 5-year survival rates were 40% and 30% in the surgical resection and RFA groups, respectively (P = 0.35).Hur et al [7] compared 42 cases of The 5-year survival rates were 50.1% and 25.5% (P = 0.0263) for surgically resected CRLM and 25 RFA-treated patients with inoperable CRLM, respectively; however, the 5-year survival rates after treatment were similar for cases with cancer foci <3.0 cm, 56.1% and 55.4%, respectively. From a surgical perspective, the authors applied RFA to the comprehensive treatment of 43 patients with CRLM ≤ 5.0 cm in diameter and ≤ 2 cancer foci, with the advantage of minimally invasive laparoscopy and RFA, and obtained a median survival time of 62 months (from CRLM diagnosis) or 56 months (from RFA treatment), with 1-, 3-, and 5-year survival rates of 100%, 82.8%, and 50.9% (from CRLM treatment), respectively. 50.9% (from CRLM diagnosis) or 100%, 80.4%, and 42.1% (from RFA treatment) of satisfactory outcomes. Based on the above data, we may think that although RFA is used for the treatment of inoperable CRLM, which is more complicated and more difficult to treat than the surgical resection group, and has a thinner basis for good outcomes, RFA treatment, especially repeated RFA treatment, can achieve outcomes similar to those of the surgical resection group; although we cannot presume from this that RFA has a place in the comprehensive treatment of CRLM Although we cannot assume the status of RFA in the comprehensive treatment of CRLM, it at least provides a sufficient basis for confidence in the further experimental application of RFA in CRLM. Strategies to improve the efficacy of RFA in CRLM To improve the efficacy of RFA in the treatment of CRLM and its status in the comprehensive treatment of CRLM, the following aspects should be done. First, it is scientific selection of cases. Combined with the successful experience of RFA for hepatocellular carcinoma, in the early stage of work, we can experimentally select cases with small diameter (no more than 5.0 cm) and small number (no more than 3) of cancer foci in order to ensure pathological complete ablation to the maximum extent. With the accumulation of experience of the treatment team, the indications can be gradually relaxed. Secondly, the RFA pathway is chosen rationally. Different pathways are suitable for different situations: the percutaneous puncture pathway is the least invasive, easy to operate, and most suitable for repeated application; its main drawback is that it is not intuitive during puncture and when releasing electrodes, with a certain degree of blindness and lack of response to bleeding at the puncture site, which can easily lead to serious complications such as intestinal fistula and biliary fistula. The laparoscopic pathway is more advantageous for exophytic or partially exophytic, multiple CRLM, allowing visualization of the lesion, potentially discovering new lesions not detected preoperatively, easily taking biopsies for examination, and allowing puncture access from different angles to obtain adequate ablation borders; it also isolates the surrounding cavernous organs from the tumor, minimizing organ damage. The open route is then suitable for larger CRLM or in combination with surgical resection. Third, complete ablation of pathology is emphasized. Pathologically, the scope of CRLM includes the main cancer foci and its surrounding micrometastases. To obtain satisfactory efficacy, in addition to ablation of the main cancer foci, there should be sufficient safe borders around the main cancer foci to ensure complete ablation of the peri-cancerous micrometastases. Fourth, standardized follow-up. the occurrence and development of CRLM is multicenter and multistage. For local treatment, standardized postoperative follow-up is more necessary to detect local residual foci, recurrent cancer foci and reoccurring cancer foci in a timely manner. Fifthly, repeated application of RFA is the best strategy to obtain complete ablation for those with large ablation area and difficult ablation location; for recurrent lesions, repeated RFA also has definite efficacy. Finally, the combination of chemotherapy is applied. The literature shows that RFA combined with chemotherapy has a good synergistic effect. Our approach is that chemotherapy is applied according to specifications. the value of FOLFOX systemic chemotherapy regimen in the treatment of CRLM has been internationally recognized as one of the standard treatment regimens; irinotecan-based FOLFORI can be used as an alternative to the failure of FOLFOX treatment. RFA can be administered opportunistically in the interval of chemotherapy cycles. As an alternative to chemotherapy, hepatic artery interventional chemotherapy has its advantages and more certain efficacy, but how to use it in combination with first-line treatment regimens requires further clinical studies. V. Outlook In summary, the use of RFA in the comprehensive treatment of CRLM is increasing and its status is becoming more prominent, but there is still a gap between its advantages and its full manifestation. In future clinical practice and research, we should pay attention to the consistency of case inclusion criteria, which is the most basic premise for assessing and comparing the efficacy of each modality; we should pay attention to the standardization at the technical level, which is the most important measure to ensure patient safety and improve the efficacy; we should pay attention to the standardization of postoperative follow-up and the effectiveness of the management of recurrent and reoccurring lesions, which is an effective guarantee to improve long-term survival; we should strengthen the CRLM Prospective studies comparing the efficacy of each treatment modality should be strengthened, which is the most powerful way to scientifically assess its clinical status. It is believed that with the gradual improvement of the efficacy of RFA in the treatment of CRLM and the accumulation of clinical experience, especially clinical evidence from large samples of evidence-based medicine, there will be a corresponding change in the treatment concept of CRLM, and the status of local treatment means represented by RFA in the comprehensive treatment of CRLM will be increasingly enhanced.