1.Clinical manifestations and diagnosis Ecker et al. believe that patients with metastatic spine tumors (MST) may have pain, neurological deficits or asymptomatic. Cancer pain is the main symptom in patients with bone metastases, mainly nocturnal pain, radicular pain is mainly from tumor compression, and spinal cord compression occurs in 5% to 10% of patients[3],Symptoms of spinal cord compression include radicular nerve pain, dyskinesia, paraplegia, and pathological fracture can occur with further damage. Spinal tumors occurring in different parts of the spine can produce corresponding pain with certain characteristic manifestations. The radiating pain produced by the tumor in the middle thoracic segment is like a girdle feeling around the thoracic back, and the pain produced by the tumor in the lumbar vertebral body can be radiated to the sacroiliac region, anterior superior iliac spine or inguinal region of one or both sides, and it produces bladder dysfunction or sexual dysfunction, which is accompanied by numbness and weakness of the thighs, then it suggests that the tumor is compressing the rounded vertebrae of the spinal cord. Lower lumbar or sacrococcygeal pain when the tumor invades the sacrum, and can radiate to the perineum or perianal area. About 40% of MST patients have unknown primary foci. Early plain film is easy to miss the diagnosis, only when the bone metastasis reaches more than 1~1.5 cm, and the decalcification reaches 50%~75%, the cancellous bone destruction reaches 30%~50% can be observed by X-ray, isotope bone scan is a highly sensitive method to detect the bone metastasis, and can detect metastatic foci 6 months earlier than the X-ray examination. CT image can observe the slight bone destruction of the spine, small soft tissue masses and vertebral body morphology, vertebral canal compression signs at an early stage, the CT manifestation of MST is classified into osteolytic, osteoblastic and mixed types as X-ray, malignant tumors originating from lungs, kidneys and gastrointestinal tracts are often osteolytic destructions, whereas the ones originating from the breasts and the prostate glands are often osteoblastic changes [4]. Magnetic resonance examination of MST has a sensitivity of 93% and a specificity of 97%, and through the T1- and T2-weighted images, the spine, spinal cord, nerves, and soft tissue involvement can be viewed from a three-dimensional space, which is an important help in understanding the whole picture of the lesion and guiding the treatment. Positron emission tomography (PET) imaging can detect metabolic abnormalities before morphological changes, which can help to detect small primary foci and soft tissue metastases that are difficult to be detected by general means, and [18F]FDG PET is considered more sensitive than bone imaging in characterizing bone metastases of nasopharyngeal carcinoma in terms of tumor staging. PET is considered to be more sensitive than bone imaging in characterizing nasopharyngeal carcinoma bone metastases in terms of tumor staging. Biopsy is required for definitive diagnosis. Staging and evaluation of MST Staging and evaluation of MST is an important step in deciding the treatment plan, Harrington et al. classified MST into 5 types according to the degree of destruction of bony structures and nerve damage. Harrington et al. classified MST into 5 types according to the degree of destruction of bony structures and nerve damage. Type I: no serious nerve damage; Type II: involvement of bony structures without vertebral collapse and instability; Type III: important nerve function damage (sensory or motor), but no obvious destruction of bony structures; Type IV: vertebral body collapses and causes pain, but no obvious nerve function damage; Type V: vertebral body collapses or is unstable, accompanied by obvious nerve function damage. It is believed that non-surgical treatment, including chemotherapy, hormone therapy and radiotherapy, is feasible for patients with type I to III; surgery is feasible for patients with type III if the spinal cord is compressed and the tumor is insensitive to radiotherapy; and surgery is performed for patients with type IV to V. Tokuhashi et al. proposed a preoperative scoring system to evaluate the prognosis and survival of MST patients: ① general health status; ② number of extraspinal metastases; ③ number of spinal involvement; ④ metastasis to important organs; ⑤ type of primary tumor; ⑥ spinal damage; each parameter has a score of 0-2 points, and a high score is a good prognosis; those who have a score of ≥9 points will undergo resection, and those who have a score of ≤5 points will undergo palliative surgery. Palliative surgery was performed for those with a total score of 6 to 8. Enkaoua et al. applied the Tokuhashi score to a retrospective study of 71 patients and concluded that the Tokuhashi score was a very effective prognostic indicator, but recommended that the score for tumors with an unknown primary focus be reduced from 1 to 0. Tomita et al [7] proposed a new scoring system for MST that included 3 prognostic factors. (i) primary tumor pathology grading: 1 point for slow growth, 2 points for moderate, and 4 points for rapid growth; (ii) organ metastasis: 0 points for no metastasis, 2 points for treatable, and 4 points for untreatable; and (iii) bone metastasis: 1 point for single or isolated, and 2 points for multiple. The total score was 10 points. For prognostic score of 2-3 points, wide resection or marginal resection was performed to obtain long-term local control; for 4-5 points, marginal or intra-lesional resection was performed to obtain medium-term local control; for 6-7 points, shorter survival was expected, and palliative surgical treatment was performed to obtain short-term local control; and for 8-10 points, only non-surgical treatment was performed. Boriani et al. used the Enneking staging for spinal tumors and proposed the WBB staging system (Weinstein-Boriani-Biagini), which includes: ① spinal cross-section is divided into 12 sectors in the clockwise direction; ② the tissue level is divided into A to E from the paravertebral region to the vertebral canal; and ③ the longitudinal extent of the tumor.WBB advocates that the resection area should be at least one level away from the tumor when incomplete resection is performed on the spine. WBB advocates incomplete resection of the spine when the resection area should be at least one sector away from the tumor, and different surgical plans are formulated according to the extent of tumor invasion: ① laminectomy (border resection of vertebral tumors) is suitable for tumors located in zones 4-8 or 5-9; ② sagittal resection is suitable for tumors located in zones 3-5 or 8-10 (centering on the pedicles); and ③ posterior arcuate resection is suitable for tumors located in zones 10-3. WBB staging provides a standardized scheme for extensive and marginal resections, which facilitates the planning of surgical access and the exchange of experience. 3.1 Systemic treatment Systemic treatment mainly includes combined chemotherapy, endocrine therapy, immunotherapy, nuclear therapy and traditional Chinese medicine for primary tumor. Bone metastases should be regarded as systemic diseases, and effective systemic therapy can eradicate the cause of bone metastases and other metastatic lesions of malignant tumors in some patients, such as breast cancer and lymphoma. Breast cancer is often sensitive to combined chemotherapy and endocrine therapy. For postmenopausal patients with positive estrogen and progesterone receptors, endocrine therapy is also a very important treatment, which can effectively control the progression of the disease and relieve cancer pain. Orchiectomy or chemical debulking of prostate cancer also has good therapeutic effect. Radionuclide is one of the methods with exact efficacy, small side effects and direct killing effect on tumor. Endoradiotherapy drugs such as 89 strontium (89Sr ) and 153Sm-EDTMP (153Sm-Ethylenediamine Tetramethylphosphonate) can effectively alleviate bone pain caused by spinal metastasis of tumor. Bisphosphonates have a high affinity for bone and are effective for osteolytic, mixed and osteogenic bone metastases. Zollefenphosphate is the third generation of bisphosphonates, which has the ability to inhibit the activity of osteoclasts and induce apoptosis of osteoclasts, and also has a direct anti-tumor effect, preventing tumor-induced osteolysis phenomenon [9], directly interfering with the process of bone resorption, with obvious pain-relieving effects, small adverse reactions, and mild renal function damage. It does not undergo biotransformation in the body, and is mainly excreted from the urine in its original form. 3.2 Local treatment Percutaneous vertebroplasty (PVP) is suitable for vertebral collapse caused by tumors, and can also be used for preventive treatment of vertebral body without obvious symptoms, but there is osteolytic destruction.PVP is used for the treatment of vertebral metastasis, 80% to 90% of patients can achieve significant pain relief within 72 h, and the effect of pain relief can be more than 70%, Alvarez can be used for the treatment of vertebral metastases, and the effect of pain relief can be more than 70%. Alvarez et al[12] applied PVP to treat vertebral metastases, 90% of the patients had immediate pain relief, and nearly 70% of the patients resumed activities away from the bed.The complication rate of PVP is 1-10%, and the most common complication is the leakage of the cement in the vertebral canal leading to the compression of the spinal cord nerve roots, followed by pulmonary embolism caused by the cement.Murphy et al[15] considered that the clinically significant complications of PVP are the following: the spinal nerve root compression due to the cement leakage in the vertebral canal, the pulmonary embolism due to the cement, the pulmonary embolism caused by the cement. significant PVP complications occur mainly in MST cases and may be related to osteolytic destruction leading to vertebral cortical defects, fractures, and injection of cement into the vertebral venous plexus.Barragan Campos et al[16] reviewed 117 patients with PVP and concluded that complications were rare, except for a few technical mishaps (cement leakage). Radiotherapy has been shown to be effective in relieving pain, reducing the incidence of pathologic fractures, and reducing tumor compression on the spinal cord. 3.3 Surgical treatment One of the main treatments for MST in the operating room. The purpose of surgery is to relieve pain, decompress the spinal cord, restore or preserve neurological function, rebuild spinal stability and improve the quality of life. The indications for surgery are: (1) patients with intractable pain that is not treated by chemotherapy, endocrine therapy or radiotherapy; (2) patients with progressive aggravation of neurological symptoms after radiotherapy; (3) tumors that are not sensitive to radiotherapy; (4) patients who need to take tumor specimens for histological examination; (5) patients who need decompression of spinal nerves when the tumor tissues are compressed by spinal nerves; (6) patients who have instability in the spinal column or extensive destruction of vertebral body structures [7, 17]. Ghogawala et al [18] developed a more intuitive surgical criteria based on the clinical manifestations of MST patients: ① pain or obvious spinal instability due to structural damage, compression; ② obvious symptomatic mechanical compression of spinal nerves; ③ progressive spinal nerve damage due to intravertebral space occupation or other compression; ④ unknown primary tumor but obvious metastatic lesions in spine; ⑤ spinal metastatic lesions that are ineffective in radiotherapy; ⑤ spinal metastatic lesions that are ineffective in radiotherapy; and ⑤ spinal metastatic lesions that are ineffective in radiotherapy. Metastatic foci in the spine which are not effective for radiotherapy; ⑥ During or after radiotherapy, the pain and neurological symptoms are obviously aggravated. The basic principles of surgery are: (1) strive for complete resection of the tumor to reduce the possibility of recurrence; (2) adopt strong internal fixation to rebuild the stability of the spine; (3) avoid damage to the spinal cord and restore or retain adequate spinal cord function. The choice of surgical access should be based on the affected segment of the spine, the size of the metastatic foci, the degree of spinal cord compression and the need for reconstruction of spinal stability. The requirements of access selection can obtain good exposure and operating space, which is conducive to tumor resection and stability reconstruction, and can be divided into anterior, posterior, and combined anterior and posterior approaches. Ernstberger et al. reviewed 24 patients with MST who underwent laminectomy with vertebral body replacement, 85% of the postoperative pain was relieved, 57.1% of the patients’ neurological symptoms were reduced, and all the patients survived for an average of 15.6 months, and concluded that the vertebral body replacement could directly restore spinal stability and reduce the symptoms related to the tumor.Guo et al[20] performed anterior laminectomy spinal structure stability reconstruction in 93 patients with MST, 87 patients (anterior and posterior) underwent anterior and posterior laminectomy spine stability reconstruction. In 87 patients (93.5%), pain was relieved and neurological function improved in 47 patients, with a one-year survival rate of 85%. The posterior approach is simple, with little tissue damage and little impact on spinal stability. Laminectomy with internal fixation was used to treat metastatic cancer of the spine, and neurological function was improved after the operation, and patients’ pain was significantly relieved. Since the spinal cord compression mainly comes from the anterior vertebral body, it is difficult to resect the vertebral body in the posterior route, and the long-term efficacy is poor. For multiple spinal metastases, the tumor involves the three column structures of the spine, and it is difficult to fully resect the tumor by anterior surgery, it is feasible to use posterior lateral approach, segmental internal fixation, and if necessary, decompression is relieved by one side transverse process and pedicle root approach, although there are certain limitations, the decompression effect in the short term is exact and reliable. Compared with simple anterior or posterior surgery, especially for patients with tumors involving vertebral bodies and accessories of the spine, combined anterior and posterior approach can achieve complete resection of the tumor, complete decompression of the spinal canal and restoration of spinal stability.Fourney et al[21] achieved good results with the combined anterior and posterior approach in 26 patients with metastatic cancer of the spine. Most of MST is located in the vertebral body, and spinal stability needs to be reconstructed after tumor resection, usually vertebral defects are reconstructed with autogenous bone, allograft bone, bone cement, and/or Cage (artificial vertebral body), and Liu et al[22] believed that anterior cervical reconstruction of structure and stability is an effective end of treatment for MST.Tao et al[23] surgically treated 63 patients with MST, and 41 patients had anterior total vertebral resection and decompression, 8 cases of anterior total vertebral resection and decompression, and 8 cases of structural reconstruction and endoprosthesis. After 63 cases of MST, 41 cases were treated with structural reconstruction and internal fixation, 8 cases were treated with laminectomy and internal fixation, 14 cases were treated with total laminectomy and decompression by single-segment anterior and posterior combined approach, and structural stability was reconstructed, and the spine was stabilized radiologically at more than 6 months of postoperative follow-up, with 57 cases having pain relief, improved quality of life, and 41 cases having neurological improvement with no serious complications. Conventional post-laminectomy defects are filled by bone cement, which can obtain both temporal stability and prevent tumor erosion, especially suitable for patients with a life expectancy of no more than 6 months, while wire or screw cement can also be applied to improve stability with adjacent vertebrae [24], for anterior reconstruction with a life expectancy of more than 6 months, direct interbody fusion and Cage can be used [25], and most scholars of posterior reconstruction favor the endofacial fixation tethered approach. Survival time of patients with metastatic cancer of the spine is related to a combination of factors such as the biological behavior of the primary tumor, therapeutic approach, and the patient’s systemic condition.Chataigner et al. reported that the mean survival of MST patients was 5.4 months for those with lung cancer origin, 5.3 months for digestive tract cancers (less than 3 months for colorectal cancers), 4 months for melanoma, 15 months for breast cancer, and 9 months for those of unknown origin. It is also related to the extent of lesion resection, 38 months for those with extensive lesions including margin resection; 30 months for those with isolated lesion resection, and 18% of those surviving more than 60 months; and only 21.5 months for those with intra-lesion resection, whereas the average survival time for patients with MST given chemotherapy alone is 14 to 18 months. The high rate of spinal metastases from malignant tumors, the specific treatment plan should be based on evaluation criteria and surgical pointers.Ecker et al[2] concluded that the optimal treatment plan for MST patients should be selected based on the assessment of neurological function, anatomical site, general health status, age and quality of life.