Neuroendocrine tumors are a rare and easily misdiagnosed type of tumor that can occur in multiple organs throughout the body, most commonly in the gastrointestinal tract and the pancreas, and the tumor that took the life of Steve Jobs, the founder of the famous Apple Inc. Neuroendocrine tumors differ from other tumors in that they are able to secrete different endocrine hormones or peptides into the bloodstream, such as insulin, gastrin, glucagon, etc., resulting in a series of clinical manifestations. Patients may experience flushing, unexplained abdominal pain, intractable diarrhea, hypokalemia and recurrent peptic ulcers, hypoglycemia, etc. When the size of tumor increases to a certain extent, symptoms related to tumor compression may also appear. For a long time, due to the lack of experience of clinicians in the treatment of neuroendocrine tumors and insufficient examination methods, this disease often becomes a “difficult and complicated disease”. Many patients have to go through 5-7 years and multiple clinical departments before they can be finally diagnosed, which is very likely to delay the diagnosis and treatment. As a result, most patients with neuroendocrine tumors are diagnosed at a late stage and have already developed local spread or even distant metastases, thus losing the opportunity for radical surgical treatment, and the most common site of metastasis is the liver. How should neuroendocrine tumor liver metastasis be treated? First of all, before any anti-tumor treatment, we need to determine the pathological diagnosis and tumor stage of the patient. The pathological diagnosis of neuroendocrine tumor is very important. pathology classifies tumors into G1,G2,G3 stages according to the Ki67 index and nuclear division image of tumor cells of patients, with increasing malignancy. patients with G1-G2 stage we usually call neuroendocrine tumor, while G3 stage is called neuroendocrine carcinoma. The clinical treatment of the three pathological stages also differs. Patients with G1/G2 stage of neuroendocrine tumors are still low-grade malignant tumors even if tumor metastasis occurs, and the prognosis of these patients is better. In contrast, patients with stage G3 neuroendocrine carcinoma who develop liver metastasis have a poorer prognosis. For patients with G1 or G2 stage, even if liver metastasis occurs, surgical resection or local treatment can be considered, and the outcome is more ideal. For a single liver metastasis, surgical resection is feasible, while ablation therapy is feasible for lesions smaller than 3 cm. For young patients (age <45 years) with resected primary tumor and no extrahepatic metastases, liver transplantation can be a treatment option with a 5-year survival rate of 48%-60%. As neuroendocrine tumors are solid tumors with rich blood supply, hepatic artery chemoembolization (interventional therapy) can achieve better outcomes for multiple or high tumor load liver metastases, with efficiency rates of 73%-100%, 57%-91% and 33%-50% for symptom relief, tumor marker reduction and imaging shrinkage, respectively, with symptom control time up to 14-22 months. For patients with liver metastases from neuroendocrine tumors in stage G3 or those with metastases from parts of the body other than the liver, systemic systemic therapy is required in addition to local treatment of the liver. The treatment differs in terms of site of development because pancreatic neuroendocrine tumors are more malignant than non-pancreatic neuroendocrine tumors. Systemic treatment of neuroendocrine tumors includes biologic therapy, systemic chemotherapy and targeted therapy. Biologic therapy: SomatostatinAnalogs (SSA), including octreotide, octreotide microspheres, and lanreotide, etc. SSA is generally used for G1/G2 neuroendocrine tumors, but may also be considered for G3 patients with positive growth inhibitor receptors, but is not preferred. Systemic chemotherapy: Streptozotocin combined with 5-FU and/or epi-amycin is used for G1/G2 neuroendocrine tumors with a tumor remission rate of 35%-40%. Temozolomide alone, in combination with chemotherapy, or targeted agents (temozolomide ± capecitabine ± bevacizumab) are indicated for G1/G2 neuroendocrine tumors. However, platinum in combination with etoposide (EP/EC) is the preferred regimen for patients with G3 neuroendocrine carcinoma, especially for patients with pathological Ki-67 >55%. While temozolomide-based regimens can be considered in the first line for neuroendocrine cancers with Ki-67 <55%, there is no accepted second-line chemotherapy regimen. A phase III clinical study compared the efficacy of sunitinib and placebo in the treatment of advanced pancreatic neuroendocrine tumors, and the median progression-free time was 11.4 months in the sunitinib and placebo groups, respectively. The median progression-free time was 11.4 months and 5.5 months in the sunitinib and placebo groups, respectively (p<0.001). Unfortunately, no further phase III clinical trials of sunitinib have been conducted in neuroendocrine tumors other than the pancreas, and therefore it is currently indicated only for patients with pancreatic neuroendocrine tumors. In 2011, everolimus completed a phase III randomized controlled clinical trial in well-differentiated (G1/G2) pancreatic neuroendocrine tumors, which was published in the New England Journal of Medicine at the same time as sunitinib. in 2015, a phase III clinical trial of everolimus in well-differentiated non-pancreatic neuroendocrine tumors was also successful. In February 2016, the FDA approved everolimus for unresectable, locally advanced or metastatic progressive, well-differentiated, non-functional neuroendocrine tumors of gastrointestinal or pulmonary origin. Therefore, for well-differentiated (G1/G2) pancreatic neuroendocrine tumors, sunitinib and everolimus are currently the first-line recommended targeted agents in the guidelines, regardless of the order of use. Soventinib is an innovative anti-cancer drug developed independently by Hutchison Whampoa Medicine, a novel oral anti-angiogenesis-immune escape kinase inhibitor with dual anti-angiogenesis and immunomodulatory activities. in June 2019, SANET-ep, a phase III clinical trial of soventinib for non-pancreatic neuroendocrine tumors as an indication, met the primary study endpoint in the interim analysis, and the study was successful ahead of schedule The study was successful ahead of schedule, filling a gap in the targeted treatment of non-pancreatic neuroendocrine tumors in China. The Phase III SANET-p study for pancreatic NETs also achieved satisfactory results and the trial data is expected to be formally presented during the annual meeting of the European Society of Medical Oncology (ESMO) in September 2020. Hutchison Pharmaceuticals has submitted a New Drug Application (NDA) for soventinib for non-pancreatic neuroendocrine tumors to the National Medicines and Drug Administration (NMPA) in November 2019 and received priority review status in December, with approval for the indication expected in the second half of this year. Immunotherapy: Immunotherapy for neuroendocrine tumors is still in clinical trials, focusing mainly on immune checkpoint inhibitors such as PD-1, PD-L1, and CTLA-4. However, available data suggest relatively limited efficacy of immune monotherapy. the KEYNOTE-028 study used pabumab to treat PD-L1-positive carcinoid or pancreatic neuroendocrine tumors with a 6-month PFS of about 40% and a 12-month PFS of 27%. The efficacy of immunotherapy alone is not optimal for slowly progressing tumors. Dual immune combination therapy improves drug efficacy, and immune combination therapy (combined with chemotherapy, targeted, and PRRT) is the direction of future research. Radioisotope therapy: Peptide receptor radionuclide therapy (PRRT) is a radioisotope therapy that is used to treat neuroendocrine tumors of the stomach, intestines and pancreas and rare thyroid cancers that do not respond to radioiodine therapy, but it is rarely performed in China. A real-world study presented at the annual meeting of the European Neuroendocrine Tumor Society (ENETS) this year showed that PRRT is effective in treating growth inhibitor receptor (SSTR)-positive neuroendocrine tumors. Another CONTROLNET study presented at the American Society of Clinical Oncology (ASCO) annual meeting suggested that PRRT combined with chemotherapy achieved higher tumor remission rates in the pancreatic/midgut NET population, but had a higher incidence of serious adverse effect (hematologic toxicity) toxicity in midgut neuroendocrine tumors. Conclusion: With the continuous development of imaging technology, there are more and more diagnostic tools for neuroendocrine tumors, and more treatment options available for neuroendocrine tumors of different grading stages or sites, driving the development of individualized treatment for neuroendocrine tumors. After metastasis of neuroendocrine tumor occurs, the combination of multidisciplinary systemic treatment and local comprehensive treatment can significantly improve the overall survival of patients, and the quality of survival will certainly be further improved.