China is a large country with liver cancer, accounting for more than 55%; of new primary liver cancer patients worldwide each year. Hepatocellular liver cancer (HCC) is the main type of primary liver cancer in China (about 95%), and because of its insidious onset and atypical early symptoms, most patients are already in the middle and late stages when they are diagnosed, and have lost the opportunity to undergo radical treatment, so their prognosis is extremely poor. Despite the emergence of new concepts, new treatments and new drugs in recent years, the efficacy of advanced hepatocellular carcinoma is still not optimistic, and the median survival time without any treatment is only 3-6 months. It is worth exploring how to reasonably utilize the existing treatments to provide comprehensive, sequential and individualized treatment for patients with advanced liver cancer in order to prolong the survival period and improve the quality of survival. 1. Concept and significance of individualized comprehensive treatment Individualized comprehensive treatment refers to an individualized comprehensive treatment plan based on patient’s specific conditions at different stages of disease development, different stages and conditions, combined with evidence-based medical evidence, with one treatment modality as the main modality and other treatment modalities as supplementary modalities, in order to achieve the purpose of maximizing the patient’s survival quality and prolonging the survival period. The general concept of advanced hepatocellular carcinoma is that the patient has lost the chance of radical treatment or distant metastasis in the developmental state of the tumor, and the course of the disease has reached the end, and the survival period generally does not exceed six months. Although the clinical application of sorafenib has brought hope to this group of patients, the overall efficacy of advanced hepatocellular carcinoma is still unsatisfactory, and it is difficult to achieve the desired efficacy by one treatment alone, and there is a lack of corresponding evidence of inquiry medicine. Meanwhile, for primary hepatocellular carcinoma, it shows obvious heterogeneity due to the differences in combined liver background diseases, presence or absence of cirrhosis and its degree, tumor size and its location, presence or absence of vascular invasion, active degree of viral replication, patients’ general status, gender, and even economic status. Even tumors of the same size may have completely different clinical manifestations, and their responses to treatment are also very different, which requires us to analyze the individual characteristics of each liver cancer patient and adopt individualized and comprehensive treatment plans in combination with various existing treatment modalities in order to prolong the survival time and improve the quality of life as much as possible. To extend the survival time of patients and improve the quality of life as much as possible. The role and value of various treatment modalities in advanced liver cancer patients The treatment methods for primary liver cancer mainly include partial hepatectomy, liver transplantation, local ablation therapy, transhepatic artery chemoembolization (TACE), radiation therapy, targeted therapy, immunotherapy, traditional Chinese medicine and so on. Individualized treatment is not an arbitrary choice of these treatments. Under the current treatment paradigm, standardized treatment should meet the requirements of evidence-based medicine, and therefore, clinical guidelines based on the best evidence are the basis for us to determine individualized treatment plans. The commonly used guidelines for liver cancer treatment include NCCN guidelines, BCLC guidelines, AASLD guidelines and so on, and our scholars have also formulated the Expert Consensus on Standardized Diagnosis and Treatment of Primary Liver Cancer according to the actual situation in China. (1) Liver resection: partial hepatectomy is still the best means to treat early stage liver cancer, but radical resection is no longer available for patients with advanced liver cancer. Liver resection plays only an auxiliary role in the treatment of advanced liver cancer, and the main purpose is to deal with complications caused by liver cancer, alleviate symptoms and reduce tumor load. For example, if the tumor is huge and compresses the surrounding organs, surgical tumor reduction can relieve the compression symptoms; if the conditions allow, palliative surgery can be performed to stop the bleeding urgently and save the patient’s life; if the liver cancer is combined with portal vein thrombosis, hepatectomy + portal vein thrombosis can prevent the cancer thrombosis from invading the portal vein, reduce the portal vein pressure, reduce the incidence of persistent ascites and ruptured esophageal varices and bleeding. In the case of hepatocellular carcinoma with multiple intrahepatic metastases, resection of the main tumor can reduce the tumor load and provide opportunities and conditions for the next comprehensive treatment. However, it is worth noting that hepatectomy is only an adjuvant means in the comprehensive treatment of advanced liver cancer, and the role of surgery should not be over-exaggerated. (2) Liver transplantation: Liver transplantation for the treatment of small hepatocellular carcinoma combined with cirrhosis has been widely recognized, but there is still a debate whether advanced hepatocellular carcinoma is suitable for liver transplantation. Most scholars believe that liver cancer, especially advanced liver cancer, is prone to recurrence after liver transplantation, and the application of postoperative immunosuppressive drugs promotes the growth of residual tumor cells, making the prognosis of liver transplantation for advanced liver cancer poor, and coupled with the shortage of donors, liver cancer should not be included as an indication for liver transplantation, and the limited donors should be given to patients with early liver cancer or benign disease who need transplantation. However, some people believe that liver transplantation provides the only measure that can prolong life and improve quality of life for patients with liver cancer, especially those with advanced liver cancer, and can be performed. In our opinion, liver transplantation is complicated and expensive, and the survival benefit for patients with advanced liver cancer is not certain, and there is still a serious shortage of donors, so liver transplantation is not recommended for patients with advanced liver cancer. (3) Local ablation therapy: Local ablation therapy is a type of treatment that directly kills tumors locally under the guidance of imaging technology, and currently radiofrequency ablation (RFA) is most commonly used. For example, in patients with multifocal lesions, the main tumor can be surgically removed and the residual lesions can be treated with intraoperative RFA, which not only reduces the damage to the residual liver, but also improves the thoroughness of treatment. RFA is also often combined with interventional treatments to improve the efficacy. (4) Transcatheter hepatic artery chemoembolization (TACE): For advanced patients who cannot undergo radical surgery, TACE is an effective palliative treatment and currently the main treatment modality for intermediate to advanced hepatocellular carcinoma. In addition to palliative treatment for inoperable liver cancer, TACE can be combined with surgery to become an important part of comprehensive treatment. Preoperative TACE can reduce the tumor size and regain the chance of surgery for some otherwise unresectable hepatocellular carcinoma. For cases with high risk of postoperative recurrence such as those with close surgical margins and satellite lesions, postoperative TACE treatment can prolong tumor-free survival time and overall survival time. (5) Radiotherapy: Modern radiobiological studies have confirmed that hepatocellular liver cancer is a radiotherapy-sensitive tumor, and its radiosensitivity is equivalent to that of hypofractionated squamous carcinoma. For patients with advanced hepatocellular carcinoma, further radiotherapy on top of interventional embolization chemotherapy can make up for the shortcomings of interventional therapy alone, thus further improving the efficacy of HCC patients. For patients with more advanced HCC, such as patients with both portal vein and inferior vena cava tumor thrombosis, radiotherapy can also prolong their survival. (6) Molecular targeted therapy: Molecular targeted therapy for tumors refers to the treatment method that kills or inhibits tumor cells by specifically acting on one or some key molecular sites in the process of tumor development. The targeted drug sorafenib has entered the clinical application stage, and its main action sites are Raf kinase in Ras/Raf/MEK/Erk pathway and VEGFR (vascular endothelial growth factor) and PDGFR (platelet-derived growth factor receptor) in vascular growth factor pathway, which can inhibit both tumor cell proliferation and tumor tissue neovascularization, and is a multi-target molecular It is a multi-targeted molecular therapeutic agent. Clinical studies have demonstrated that sorafenib significantly prolongs progression-free survival and overall survival in patients with inoperable advanced/progressive hepatocellular carcinoma. Targeted therapy can be used for patients with advanced progressive HCC who cannot receive radical treatment such as surgery and radiofrequency ablation, or in combination with other palliative treatment modalities such as TACE, depending on the patient’s wishes and financial status. In the experience of using in the Cancer Hospital of Medical Academy, there are patients with advanced hepatocellular carcinoma who have been treated with targeted therapy, the tumor shrunk significantly and got the chance of surgery. (7) Systemic chemotherapy: In the past, advanced hepatocellular carcinoma was thought to be highly resistant to cytotoxic chemotherapeutic agents. The literature reports that the objective efficiency of single drug or combination chemotherapy of systemic chemotherapy is low and fluctuates greatly (0-25%;), which is mainly due to the existence of primary drug resistance in HCC and the fact that most of HCC occurs on the basis of pre-existing liver disease, with impaired liver function, poor tolerance to chemotherapy drugs and difficulty in achieving the optimal dose of administration. In recent years, the widespread use of some new highly effective and less toxic chemotherapeutic drugs and the increasing level of clinical research have made the traditional concept that HCC is not suitable for systemic chemotherapy questionable and challenging. It is worth mentioning that the success of a large phase III clinical study (EACH trial) of FOLFOX 4 regimen for hepatocellular carcinoma led by Chinese scholars has demonstrated significant benefits of systemic chemotherapy for advanced HCC in terms of disease control rate, progression-free survival, overall survival and safety, changing the status quo of lacking standard regimens for systemic chemotherapy in advanced HCC. It is believed that systemic chemotherapy will occupy an important place in the comprehensive treatment of advanced HCC. (8) Other treatment methods: including hormone therapy, immunotherapy, Chinese herbal medicine, etc., are still not very effective and play only an auxiliary role in the comprehensive treatment of advanced hepatocellular carcinoma. The overall prognosis of patients with advanced hepatocellular carcinoma is not optimistic, and it is difficult to achieve the effect of cure with any current treatment measures. Many treatments may be accompanied by many adverse reactions while prolonging patients’ survival, and cause huge financial burden to patients and families. Therefore, only by carefully assessing the patient’s disease status and taking into account the patient’s family and financial situation as well as the patient’s requirements and expectations for treatment can the physician make a reasonable individualized and comprehensive treatment plan. It is worthwhile for every oncologist to think about how to make patients have a high quality of life with a long survival period. It should also be pointed out that the current individualized treatment plan is still formulated by doctors combining their own clinical experience and patients’ clinical performance, and lacks high-level evidence-based medical evidence and standardization. Individualized treatment based on molecular typing of hepatocellular carcinoma is the direction of future development, but the current research base in this area is still very weak, and there is still a long way to go to achieve true individualized treatment.