Primary liver cancer (PLC) is one of the most common malignant tumors in clinical practice, with a global incidence of more than 620,000/year, ranking 5th among malignant tumors, and nearly 600,000/year, ranking 3rd among tumor-related deaths. It ranks second after lung cancer in tumor-related deaths. Therefore, liver cancer is a serious threat to people’s health and life in China. In order to promote the development of clinical oncology in China, improve the level of multidisciplinary standardized and comprehensive treatment and research of PLC, actively study and apply high-level evidence from domestic and foreign countries in accordance with the principles of evidence-based medicine, and formulate clinical practice guidelines for PLC in accordance with the national conditions of China, the Chinese Anti-Cancer Association Liver Cancer Specialty Committee (CSLC), the Collaborative Specialty Committee of Clinical Oncology (CSCO) and the Chinese Medical Association Liver Disease The Chinese Anti-Cancer Society Hepatology Committee (CSLC), the Collaborative Clinical Oncology Committee (CSCO) and the Hepatology Group of the Chinese Medical Association Hepatology Branch jointly initiated the development of this “Expert Consensus on Standardized Diagnosis and Treatment of Primary Liver Cancer” with the participation of multidisciplinary experts.
On November 10, 2007, April 5, 2008 and August 30, 2008, three expert consensus seminars were held in Shanghai. The meetings were co-chaired by Professors Ye Shenglong and Qin Shukui, with the personal guidance of Wu Mengchao, Tang Zhaoyou, Sun Yan and Guan Zhongzhen, and attended by more than 60 renowned experts in the field of PLC diagnosis and treatment in China. At the meeting, the current international guidelines and consensus on PLC were systematically reviewed, and a series of issues such as diagnosis, surgical treatment (liver resection and liver transplantation), interventional treatment, local ablation treatment (mainly including radiofrequency ablation, microwave ablation and high-intensity focused ultrasound treatment), radiotherapy, biological treatment, molecular targeted therapy, systemic chemotherapy and Chinese medicine treatment were discussed. The experts prepared and actively participated in the meeting, based on the principle of respecting evidence-based medical evidence and aligning with international diagnostic and therapeutic concepts, especially for the current situation and development of PLC diagnosis and treatment in China, they expressed their opinions and brainstormed, and put forward many good suggestions. After the meeting, this consensus was finally formed by some experts penning the paper, widely soliciting opinions and repeatedly revising it many times.
Since most of the PLC are hepatocellular carcinoma (HCC), clinical management involves many disciplines such as medical, surgical, interventional, radiotherapy, Chinese medicine and medical imaging, etc. Therefore, the standardized diagnosis and treatment of hepatocellular carcinoma needs to be discussed and formulated by multidisciplinary experts in order to select the most suitable preferred treatment and comprehensive treatment measures for patients after diagnosis. Currently, there are international guidelines for the treatment of liver cancer that can be used for reference, mainly including.
① Clinical practice guidelines for liver cancer from the National Comprehensive Cancer Network (NCCN).
②The American Association for the Study of Liver Diseases (AASLD) clinical treatment guidelines for HCC.
③The British Society of Gastroenterology (BSG) treatment guidelines.
④ Consensus developed by the American College of Surgeons (ACS); covering the staging, surveillance, screening, diagnosis and treatment of hepatocellular carcinoma.
(I) Staging of hepatocellular carcinoma
For the staging of HCC, there is no uniformity in the AASLD, ACS and NCCN guidelines, and the emphasis is not the same. Among them, the TNM staging approach adopted by NCCN is the most standardized internationally, but is less recognized because of the following reasons.
(i) vascular invasion, which is crucial to the treatment and prognosis of HCC, is difficult to determine accurately before treatment (especially before surgery).
(ii) Treatment of HCC places great emphasis on liver function compensation, while TNM staging does not indicate the patient’s liver function status.
(③) The variability of TNM staging among versions is large and difficult to compare and evaluate. AASLD adopts the Barcelona Liver Cancer Center (BCLC) staging and treatment strategy, which takes into account tumor, liver function and systemic conditions in a more comprehensive manner and is supported by high-level evidence of evidence-based medicine, and is now more recognized and widely adopted worldwide.
(II) Surveillance and screening of hepatocellular carcinoma
The four international guidelines mentioned above all emphasize early screening and early surveillance of HCC, which are based on evidence-based medical evidence and have a high degree of credibility. The views on screening indicators are relatively consistent and mainly include two items: serum alpha-fetoprotein (AFP) and liver ultrasonography. For men ≥ 35 years of age with HBV and/or HCV infection and a high risk of alcoholism, screening is generally performed at 6-month intervals. For AFP > 400 μg/L without liver occupancy on ultrasound, care should be taken to exclude pregnancy, active liver disease, and germinal gland tumors of embryonic origin; if this can be ruled out, CT and/or MRI should be performed. If AFP is elevated but not at the diagnostic level, in addition to the above-mentioned conditions that may cause increased AFP should be excluded, the dynamic changes in AFP should be closely tracked, the interval between ultrasound examinations should be shortened to 1~2 months, and CT and/or MRI examinations should be performed when needed. If hepatocellular carcinoma is highly suspected, DSA hepatic artery iodine oil angiography is recommended.
(C) Diagnosis of hepatocellular carcinoma
The diagnostic criteria of HCC include pathological and clinical diagnostic criteria. The diagnostic methods include serum tumor marker (AFP) testing, imaging examinations (including ultrasonography, CT, MRI and DSA angiography) and pathological histological examinations (mainly liver tissue biopsy). the BSG guidelines suggest that for patients with cirrhosis, the presence of cirrhosis is first determined, followed by a threshold of 2 cm of occupancy size to start the diagnostic process; while for non-cirrhotic patients, the AFP level is used to guide the diagnostic process. The diagnostic process of AASLD has been applied internationally more often, differentiating between the mass and the diagnostic process by occupancy <1 cm, 1 to 2 cm and >2 cm, with emphasis on early diagnosis.
(D) Treatment of hepatocellular carcinoma
The consensus of ACS states that the treatment goals of HCC include: cure; local control of tumor and preparation for transplantation; local control of tumor and palliative care. Improving the quality of life is also one of the important treatment goals. The NCCN emphasizes the importance of keeping abreast of the times while following evidence-based medicine, and its 2008 edition has introduced the last two years of breakthroughs in the treatment of hepatocellular carcinoma. breakthroughs, namely, the molecular targeted therapy drug sorafenib is listed as one of the standard treatment options for patients with inoperable and advanced HCC.
Diagnosis of primary liver cancer
(I) Early diagnosis
Early diagnosis is crucial. Since the 1970s to 1980s, the early diagnosis of PLC has been greatly facilitated by the gradual popularization and wide application of serum AFP, real-time ultrasound imaging and CT. As the early diagnosis rate has increased significantly, the surgical resection rate has increased and the prognosis has been improved significantly; therefore, the diagnosis of PLC, especially the early diagnosis, is the key to clinical treatment and prognosis.
In terms of early diagnosis, full attention should be paid to the background of liver disease of patients. In China, 95% of PLC patients have a background of hepatitis B virus (HBV) infection, 10% have a background of hepatitis C virus (HCV) infection, and some patients have overlapping HBV and HCV infection. Special attention should be paid to the following risk groups: middle-aged and elderly men with high HBV load, HCV-infected patients, HBV and HCV overlapping infections, alcoholics, co-infected diabetics, and those with a family history of liver cancer. After the age of 35-40, these people should undergo regular screening (including serum AFP test and liver ultrasound) every 6 months; when there is an elevated AFP or “occupying lesion” in the liver area, they should immediately enter the diagnostic process, observe closely and strive to make early diagnosis.
(II) Laboratory diagnosis methods of liver cancer
At present, the qualitative diagnosis of hepatocellular carcinoma in China is still based on the detection of serum AFP, which should be highly regarded.
(1) In China, more than 60% of liver cancer cases have serum AFP > 400μg /L.
(2) There are no other tumor markers with specificity comparable to that of AFP.
(3) AFP detection is less dependent on imaging equipment and new technologies.
(3) Diagnostic imaging methods for hepatocellular carcinoma
In recent years, the progress of medical imaging examination methods is obvious, and the “four definitions” of PLC in clinical practice are as follows