On December 7, 2019, the National Health Commission officially issued the "Norms for the Diagnosis and Treatment of Primary Liver Cancer (2019 edition)" (hereinafter referred to as the "Norms"). Under the guidance of the National Health Commission, led by Academician Fan Jia of Zhongshan Hospital Affiliated to Fudan University, a total of more than 70 experts in the field of liver cancer diagnosis and treatment actively participated in the code, which was finally released after more than 10 months. The new version of the Code pays more attention to updating based on clinical evidence-based evidence. In order to help the majority of clinicians deeply understand the relevant contents of the "Code", this newspaper invited experts in various fields of the "Code" formulation expert group to interpret the 7 aspects of imaging, pathology, surgery, interventional, radiology, internal medicine and traditional Chinese medicine.

Local treatment of liver cancer represented by radiofrequency and microwave has the advantage of minimally invasive and efficient, and has become one of the three radical treatment methods for early liver cancer as an indispensable treatment method in the multidisciplinary treatment of liver cancer. In this issue, we invite Professor Chen Minshan, deputy leader of the Internal medicine and local treatment Group of the Expert Committee on the preparation of the "Standard", and hepatobiliary Department of Sun Yat-sen University Cancer Prevention and Control Center, to interpret the local treatment of liver cancer.

The efficacy of radiofrequency ablation was further confirmed

Local ablation, represented by radiofrequency ablation (RFA), has been developed in clinical application and technology for more than 20 years, and its technology, method and efficacy have been mature and recognized.

Among them, three prospective randomized controlled clinical studies from China compared the effect of RFA and surgical resection in the treatment of small liver cancer, and confirmed that RFA can be used as a radical treatment other than surgical resection. At the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, a national multi-center clinical trial (SURF trial) from Japan compared RFA with surgical resection for small liver cancer. The study plans to enroll 600 cases of small liver cancer in multiple centers across Japan (number ≤3; Patients with maximum diameter ≤3 cm were randomized 1:1 for surgical resection or RFA treatment. At the annual meeting, we reported a preliminary outcome analysis of 308 patients who had completed treatment so far, showing no statistically significant difference in 3-year relapse-free survival (RFS) between surgical resection and RFA: 49.8% and 47.7%, respectively. There was no significant difference in the incidence of surgical complications and surgery-related mortality. In the radiofrequency treatment group, surgery time and hospital stay were shorter. The preliminary results of this high-quality multicenter RCT study reconfirm the efficacy and status of RFA in the treatment of small liver cancer, as well as its minimalism and safety relative to surgical resection.

Therefore, the "Norms" point out that for patients with early liver cancer who can be surgically resected, RFA has similar or slightly lower DFS and overall survival (OS) rates, but lower complications and hospital stay than surgical resection. The efficacy of RFA is similar to or superior to surgical resection for a single liver cancer ≤2 cm in diameter, especially for central type liver cancer. For patients with early liver cancer that cannot be resected surgically, RFA has a radical effect and should be recommended as a first-line treatment.

In recent years, with the popularity of laparoscopic hepatectomy, many early liver cancers can be cured by laparoscopic minimally invasive resection, which not only obtains the effect of surgical resection, but also has the advantage of minimally invasive resection. Therefore, laparoscopic hepatectomy is increasingly accepted as the treatment of choice for early liver cancer. However, we believe that local ablation therapy can still be used as the preferred treatment for small liver cancer in the following situations:

1) Inoperable/inoperable small liver cancer;

2) Small liver cancer ≤2cm;

3) Central small liver cancer;

4) Multiple small liver cancer;

5) Recurrent small liver cancer.

For the ablation of larger tumors, it is necessary to combine other therapeutic approaches. Hepatic arterial chemoembolization (TACE) plus local ablation is the most commonly used combination therapy and has been repeatedly shown to be superior to ablation alone or TACE. Other combination regimens, such as ablation plus targeted therapy, are still being explored.

The effect of microwave ablation is similar to that of radio frequency ablation

Due to various reasons, microwave ablation was only widely used in Japan and China in the early stage, and was less used in Europe and the United States. In recent years, with the improvement of microwave ablation technology and the deepening of clinical research, microwave ablation has been gradually accepted in Europe and the United States. At present, most clinical and basic studies believe that microwave ablation and radiofrequency ablation are almost the same in terms of therapeutic effect, safety and operation convenience.

Microwave ablation has its own advantages

It has high ablation efficiency, short ablation time, and can reduce the "heat sink effect" of radiofrequency ablation, showing advantages for large tumors with abundant blood supply and adjacent vascular tumors, and has advantages in the ablation treatment of liver metastases.

Microwave ablation also has its disadvantages

The ablation range of single needle is irregular, and there is a "tailing" phenomenon. The ablation power is high and the heat is sufficient, which is easy to cause damage to the surrounding organs. The evidence-based medical evidence for radiofrequency ablation is more sufficient, while microwave ablation needs more and larger clinical studies to support. Therefore, the surgeon should choose a more appropriate ablation method based on the size, nature and location of the tumor, as well as the operator's experience.

The role of external radiation therapy has been emphasized

With the widespread application of stereotactic body radiotherapy (SBRT) in the treatment of liver cancer, the role of SBRT in the treatment of liver cancer has been paid more and more attention. The National Comprehensive Cancer Network (NCCN) Guidelines (2018 edition) have also listed SBRT and ablative therapy as local treatment options for liver cancer.

Japanese scholar Sanuki N et al. reported the efficacy of the largest SBRT in the treatment of small liver cancer at present, with a 3-year OS rate of 70%, and the effect is encouraging. The American Journal of Clinical Oncology (J Clin Oncol) also reported two retrospective control studies of SBRT compared with RFA in the treatment of liver cancer in 2016 and 2018 respectively. Although the results of the two studies reported some differences, the effect of SBRT in the treatment of liver cancer, especially small liver cancer, has been very close to that of ablative therapy.

Therefore, this Code also keeps up with the progress of The Times, expands the indications of radiation therapy, and clearly points out that HCC SBRT can also be considered as an alternative treatment for CNLC patients with stage Ⅰa and partial Ⅰb liver cancer, if there is no indication of surgical resection or local ablation, or if they are unwilling to accept invasive treatment.

The application of external radiation therapy in liver cancer conversion therapy and palliative care is also increasing gradually. A study from Shanghai Oriental Hospital of Hepatobiliary Surgery showed that for palliatively resectable patients with advanced liver cancer complicated with portal vein cancer embolus, 18 Gy neoadjuvant external radiation therapy before surgery can significantly reduce the recurrence rate after palliative resection, and DFS increases from 3.3% to 13.3% in 2 years. Improved OS rate, from 9.4% to 27.4% in 2 years, without increasing the incidence of surgical complications; It suggests that the role of external radiation therapy in neoadjuvant/conversion/descending therapy is worthy of further study.

Author | Yaojun Zhang and Minshan Chen (Hepatobiliary Department, Cancer Prevention and Control Center, Sun Yat-sen University)

Editor | Hao Ran (China Medical Tribune)