Bone is the third most frequent site of malignant metastasis, after lung and liver. The main complication of bone metastasis cancer in limbs is pathological fracture, the incidence rate is about l0-30%, mostly in long bones, among which femur is the most common. Among the primary tumors causing pathological fractures, breast cancer is the most common (about 60%), followed by lung cancer, then prostate cancer and kidney cancer. The proximal femur is one of the favored sites for metastatic cancer, and the risk of pathological fracture is high here because of the high-intensity biomechanical load transmitted in this region. Fifty percent of pathologic fractures of the proximal femur are located in the femoral neck, 30% in the subtrochanter, and 20% in the intertrochanter [3]. Patients with pathological fractures or near fractures often require therapeutic or prophylactic internal fixation or prosthetic arthroplasty with the goal of reducing pain, restoring function, and improving quality of life as soon as possible. In this article, we systematically review the preoperative evaluation, surgical treatment, and comprehensive treatment of patients with metastatic carcinoma of the proximal femur. The evaluation of metastatic cancer of proximal femur is more or less the same as that of metastatic cancer of other extremity bones, including preoperative patient’s surgical indications, expected survival time and assessment of imminent fracture. Preoperative patient indication assessment The overall condition of patients with metastatic cancer to the proximal femur is correctly assessed through a comprehensive medical history and physical examination. Surgical versus non-surgical treatment depends on the location of the lesion, tumor type, tumor size and general status of the patient. The type of tumor is an important basis for evaluating the surgical approach, which determines the length of patient survival, intraoperative bleeding and the extent of bone destruction. The size and extent of the tumor is also an important factor in the preoperative evaluation. In addition to plain radiographs, preoperative MRI can assess the extent of tumor involvement in the medullary cavity and also identify soft tissue invasion. Bone scan and MRI can suggest multiple lesions on the same bone. Surgery can usually be performed if the patient is in good overall condition, tolerates surgical trauma, and cooperates well with treatment and rehabilitation. The most commonly encountered relative contraindications to surgical treatment are a dying disease state, infection in the surgical area, acute deep vein thrombosis (especially with pulmonary embolism), extensive vascular nerve bundle invasion due to soft tissue tumor enlargement, generalized weakness that prevents the patient from tolerating surgical treatment, or a patient with a short survival expectancy and little benefit from surgical treatment. Contraindications sometimes depend on patient characteristics, disease characteristics and surgical approach characteristics. Patient needs should also be considered. The patient’s entire physical and mental status, his or her desire and ability to participate in rehabilitation should also be considered. 2. Assessment of expected survival time There are also many reports on the assessment of survival of patients with bone metastases, but most of them focus on spinal metastases. The Dutch model scoring system is more commonly used in clinical practice to assess survival. This score predicts survival based on the Kamofsky Performance Scale (KPS), the primary site, and the involvement of internal organs. The prognosis was divided into three groups based on the results: group A, with a total score of 0 to 3 and a median survival of 3 months; group B, with a total score of 4 to 5 and a median survival of 9 months; and group C, with a total score of 6 and a median survival of 18.7 months. The actual survival of patients is difficult to predict, but often exceeds the expected survival. 3. Assessment of near fractures The earliest studies on the assessment of near fractures were in 1956 and 1961 when Snell and Beals et al. reported 19 patients with pathological fractures of femoral metastases from breast cancer. In 1970, Parrish and Murray reported their experience in treating 104 patients with metastatic bone cancer. The indications for prophylactic internal fixation of near fractures of the femoral stem were progressive cortical destruction and progressively increasing pain with cortical destruction greater than 1/2 diameter. In 1974, Murray et al. discussed the surgical treatment of secondary pathologic fractures of the hip. It concluded that prophylactic internal fixation was feasible in cases where the bone destruction was greater than 1/3 of its diameter. Increased pain and insensitivity to radiotherapy were their reference factors. However, there is also no clear basis for its such conclusion.Zickel and Mouradian tried to clarify the characteristics of the lesions in the subrotor region where fractures may occur. They retrospectively analyzed 34 patients and proposed the following criteria for high risk of pathologic femoral fracture: (1), radiographs were purely osteolytic destruction; (2), malignant lesion destruction of the femur not preceded by other bones; (3), involvement of part of the cortex; (4), progressive pain. In particular, when the lesion presented as a florid pattern on radiographs, they considered lung cancer metastasis to the subrotal region as high risk and breast cancer as low risk; the presence of more than one high-risk factor in the patient was an indication for prophylactic fixation. fidler analyzed 66 patients with 100 long metastatic bone cancers. He measured the size of the lesion and calculated the percentage of the long bone diameter it occupied. His study showed that fractures rarely occurred when the bone destruction was less than 50% of the diameter (2.3% of fractures). When the bone destruction was greater than 75% of the diameter, fractures were likely to occur (fractures in 80% of cases). Analysis of the primary lesion did not show any difference, nor was there a significant difference in the incidence of fractures in metastatic carcinoma of the upper and lower extremities. In 1982, Harrington [12] described the characteristics of near fractures. He considered femoral lesions of 2.5 cm or more in diameter, osteolytic destruction greater than 50% of the long bone cortex, and weight-bearing persistent pain after radiation therapy as characteristics of near fracture. They concluded that future studies should establish criteria for the assessment of fracture in metastatic femoral cancer. The most commonly used criterion for assessing near fractures is the Mirels scoring system, which has a 12-point scale based on anatomic site, type of bone destruction, degree of destruction, and pain associated with activity. A composite score of 9, 8, and 7 is associated with a fracture incidence of 33%, 15%, and 4%, respectively. Therefore, prophylactic fixation is performed in patients with bone metastases with a near fracture score of 8 or higher. Although the Mirels’ scale provides a good guide for physicians in the treatment of patients with metastatic cancer who are at risk of fracture, it is based on 78 radiation-treated patients, a small number of patients, and is a retrospective study, and there is overlap between the fracture and nonfracture groups. Van der Linden et al. concluded that only longitudinal femoral cortical damage greater than 30 mm (P=0.01) and cortical involvement greater than 50% of the cortical ring length (P=0.03) could predict fracture, whereas the Mirels’ scoring system did not have sufficient specificity to predict fracture (P=0.36). Also, the clinician’s experience is important. Prophylactic internal fixation should be performed in radiotherapy-insensitive patients with progressive pain, regardless of the Mirels’ score. The proximal femur is at high risk of pathologic fracture due to its special anatomical location, high intensity stress transmission, and metastatic carcinoma of the femoral neck, intertrochanteric and subtrochanteric, which should be prophylactically fixed as early as possible. The first principle is that the recovery period after surgery should be shorter than the expected survival time of the patient; the second principle is that the fixation provided must be stable enough to provide full weight bearing and continuous stability during the patient’s survival; the third principle is that the surgical reconstruction needs to cover all the destroyed bone. Surgery should be considered in the context of the fracture site, the bone destruction, the general condition of the patient, and the expected survival time. Unlike non-pathologic fractures, pathologic fractures often take longer to heal, and nearly 50% of fractures do not heal at all; Gainor and Buchert et al. found a 44% healing rate for bone metastases from renal cell carcinoma and a 37% healing rate for pathologic fractures from bone metastases from breast cancer. Patients with bone metastases from lung cancer did not heal after fracture until the end of life. Therefore, the strength of the internal fixation must be sufficient to maintain this non-healing or delayed healing for the limited survival time of the patient. In addition, because of the limited survival time of these patients, the goal of treatment should be full weight bearing immediately after surgery in order to improve the patient’s quality of life. With the continuous improvement of medical treatment, including chemotherapy, radiation therapy and external radiation therapy with additional application of diphosphonates, the survival of patients with bone metastases is significantly increased than in the past, which requires more durable and strong stability of internal fixation. Steel plate screw fixation Steel plate can be effectively applied to treat epiphyseal and metaphyseal bone destruction. Successful plate fixation requires two important prerequisites. First, the adjacent articular surface must be intact and have some functional range of motion and no pain. Second, there must be sufficient remaining bone to obtain the desired stable fixation and to allow immediate postoperative weight bearing. At least one side of the cortex must be able to withstand physiological loading after complete and strong fixation. This may be more useful for near fractures. However, plate fixation is much less frequently applied to the proximal femur than to the distal femur. Biomechanically, plates and screws do not have the strength of intramedullary fixation and may fail in the treatment of pathologic fractures; Yazama et al. reported a 23% failure rate with compression screws and plate fixation in the treatment of metastatic cancer of the proximal femur. A potential complication of plate fixation is increased stress at the end of the plate. Failure of plate fixation is common if the disease progresses and metastases develop in other areas of the femur. If replaced with intramedullary fixation, it is more difficult to remove the plate, screws and cement. For pathological fractures or near fractures of the intertrochanteric space caused by metastatic cancer, powered hip screws have been used in the past to preserve hip function. However, this method often does not provide stable fixation and often requires secondary surgery due to internal fixation failure. In patients with lesions located in the intertrochanteric region and with less medial cortical destruction, powered hip screws and lateral plates were traditionally applied. However, prolonged survival, local disease progression, weak internal fixation, delayed healing or nonhealing, and lack of stress sharing between the endophyseal and residual bone can increase the failure rate of this fixation. The application of bone cement is important when applying hip screws and plate fixation. Usually a window is made in the lateral bone wall and the bone cement is placed. It is still controversial whether the cement is placed before the plate and screw or the opposite injury. Proponents believe that placing the cement first and then the screws allows the screws to be buried in the cement rather than in the poorer bone. The screw threads combined with the bone cement provide a larger contact surface for the fixation, reducing the risk of screw extraction from the femoral head. Opponents argue that drilling of the femoral head may lead to osteonecrosis or release of cement microemboli into the rich vascular plexus near the femoral head. Filling the distal medullary cavity with bone cement can also increase the strength of screw and plate fixation. 2. Intramedullary nail fixation Intramedullary nails have the biomechanical advantage of being placed more medially close to the pressure side of the femur away from the tension side. The application of interlocking intramedullary nail for proximal femoral metastatic cancer is not very large. Interlocking intramedullary nailing is suitable for metastatic cancer damage in the subtrochanteric region and femoral cadre. For subtrochanteric adjacent fractures, intramedullary nailing with or without cement filling is often used. Zickel and Mouradian et al. reported the successful treatment of 35 patients with subtrochanteric and pathologic fractures using the Zickel intramedullary nail. All patients were able to walk and exercise early. However, since the locking nail above it goes from the greater trochanter to the lesser trochanter. It does not provide protection of the femoral neck or the intertrochanteric region, the interlocking intramedullary nail is more suitable for the treatment of metastatic cancer of the femoral stem. The intertrochanteric ridge and the base of the femoral neck are the most frequently invaded areas of metastatic cancer, so invasion of these areas occurs as the disease progresses. Therefore, a reconstructive nail may be a better option, with two locking nails entering the femoral neck through the trochanter on the one hand, and a distal locking nail locked to the distal femur on the other hand, suitable for both proximal femur endangered fracture prevention and metastatic cancer treatment of the stem, providing protection of the full length of the femur against rotational and angular displacement. If the fracture takes a long time to heal or eventually does not heal, it is recommended that locking nails be applied to all locking holes on the primary nail to increase stability. Reconstructive nails can be placed percutaneously unless there is a large defect to be scraped. If intracapsular scraping of the lesion is required, the lesion is often scraped prior to reaming and insertion of the intramedullary nail to prevent tumor implantation and dissemination within the medullary cavity. 89 cases of the femur were treated by Ward et al. with good results, including 69 pathologic fractures and 20 near fractures, using reconstructive nailing. Retrograde femoral intramedullary nailing is hardly used in metastatic cancer of the proximal femur. In these patients, it does not provide protection of the femoral head, neck, intertrochanteric and subtrochanteric. Proximal locking increases stress concentration and also predisposes to fracture, and the proximal locking area is also a good site for metastatic cancer. Recent applications of proximal femoral intramedullary nailing for the treatment of traumatic proximal femoral fractures also have their applications. These include PFN, PFNa, and Gamma nails. For these intramedullary fixations, they may be appropriate in patients with intertrochanteric metastatic carcinoma alone, with no lesion destruction under the trochanter or in the femoral stem. However, short intramedullary placed intramedullary nails of the proximal femur often present problems at the tip of their cadaver, especially if the patient has a long survival and a new metastatic cancer lesion develops far from the tip of their fixation. Although both types of internal fixation have their elongated intramedullary fixation, their literature reports are scarce, and their distal locking is usually without navigation or targeting devices and relatively complicated to operate. 3. Arthrodesis Arthrodesis should be performed for pathologic fractures of the femoral head and neck verging on fracture, especially in this region. The high stresses transmitted through the proximal femur, combined with its limited healing capacity, result in a high rate of internal fixation failure, even in less demanding patients. Moreover, pathologic fractures of the femoral neck rarely heal within the patient’s expected survival time and in some cases are associated with severe bone loss. There are many reports of excellent outcomes after prosthetic replacement. lane et al. reported 167 patients with pathologic fractures or near fractures of the hip who underwent built-in prosthetic replacement. All patients had a significant reduction in pain. For patients who were able to walk before the pathological fracture, 3/4 of the patients had significantly enhanced motor function with long-stemmed or total hip replacements. Cemented hemiarthroplasty is suitable for patients with pathological fractures or extensive damage to the femoral neck, head or intertrochanteric space. It facilitates early postoperative radiotherapy and reduces the effect on fracture healing during internal fixation. There are many reports of success. Artificial prosthesis replacement reconstruction for the treatment of pathological fractures of the proximal femur is not dependent on bone healing and can restore function, reduce pain and provide stable reconstruction as early as possible. In addition, prostheses are used to remedy patients with failed internal fixation and postoperative inability to treat with radiation. There is controversy as to whether to perform total hip replacement and hemi-arthroplasty for femoral head involvement. Because both procedures have been reported to be successful, there have also been reports of persistent pain and high failure rates after hemiarthroplasty. A preoperative CT or MRI of the acetabulum would be helpful if plain radiographs reveal a problem with the acetabulum. If the acetabulum is in compromise, an acetabular prosthesis may be applied. If total hip arthroplasty is applied, bone cement should be applied to both the acetabular and femoral head prostheses for postoperative radiotherapy. Extensive damage to the acetabulum can be treated with an anti-dislodgement cup, a saddle-type prosthesis or an acetabular prosthesis placed with bone cement and reinforced with a S-type nail (Harrington method). When there is extensive bone destruction or defect in the periacetabular region, a conventional proximal femoral prosthesis may not be suitable for treatment, and then a custom-made prosthesis or a modular prosthesis for proximal femoral replacement (also called a tumor prosthesis) may play a greater role. However, its soft tissue reconstruction is quite important. Articular capsule preservation and soft tissue repair are essential. Assembled prostheses are very effective in the treatment of malignant tumors of the proximal femur. selek et al. applied prosthetic replacement to treat 44 patients with proximal femoral replacement cancer. It concluded that built-in prosthetic reconstruction for metastatic carcinoma of the proximal femur could provide early and stable fixation while reducing pain and obtaining good function. Care should be taken to protect the soft tissues surrounding the tumor prosthesis when it is applied, as it usually takes 6-8 weeks to fully heal. Dislocation occurs frequently due to weakness of the adductor muscle. Disadvantages also include postoperative infection and decreased strength of the hip flexors and abductors leading to persistent gait instability. Despite the high complication rate, immediate postoperative weight bearing alleviates pain. For some patients with metastatic cancer in the proximal femur, if the primary focus is renal cell carcinoma, it is expected that there will be a lot of bleeding from the scraping of the lesion during the operation, if it is single, the whole block can be excised and then the tumor-type prosthesis can be reconstructed. 4. Application of bone cement Although there is no statistical data on metastatic cancer with a lot of lesion scraping and bone cement filling, most bone oncologists recommend the application of bone cement. For patients with large soft tissue masses and bone destruction greater than 50% of the host bone, scraping of the tumor tissue and filling with bone cement is useful. In addition, if the fracture end defect is large, cement filling and bridging may reduce the failure rate of the internal fixation. The application of bone cement to the lesion site is also important when applying intramedullary nailing. Scraping of the lesion should be performed through a separate incision prior to intramedullary nail insertion. After scraping, the intramedullary nail is inserted, marked to the appropriate depth, and then the intramedullary nail is withdrawn proximal to the lesion, at which point the defect is filled with bone cement and the intramedullary nail is inserted. Antibiotics may be added to the bone cement as appropriate. The bone cement may also kill the tumor cells within the lesion through its thermal damage. In addition, this thermogenic effect may reduce bleeding. III. Comprehensive treatment Radiotherapy and other adjuvant treatments for proximal femoral metastases are the same as those for other skeletal metastases of the extremities. In a retrospective study conducted by Townsend et al, 15% of patients who received only surgical treatment without radiotherapy required revision surgery due to pain and loosening of the prosthesis, and only 3% of patients who received postoperative radiotherapy required secondary surgical treatment. Postoperative radiotherapy is usually administered within 2-4 weeks after surgery, with most patients undergoing it after the incision has healed. A total of 3000 cGY is usually chosen for 10 applications, covering the lesion site, the surgical field, the full length of the prosthesis, and the entire medullary cavity if the medulla is expanded. The British Surgical Oncology Society guidelines are to give 2000 cGY in 5 postoperative doses. Patients with bone metastases from renal cell carcinoma are irradiated at an increased dose (4500 cGY total/180 cGY each). In general, it is much easier to prevent fractures than to treat pathologic fractures to heal, especially in patients requiring radiotherapy. Radiotherapy may delay fracture healing and increase the risk of wound complications and infection. Radiotherapy is also used primarily for pain relief. Currently, a variety of drugs are available, with phosphorus 32 (32P) and trance 89 (89Sr) being used more frequently because of their longer half-lives (up to 12 and 50 d, respectively) than samarium 153 (153 Sm) and rhenium 186 (186 I ). Since the radiopharmaceuticals are located mainly in the normal bone surrounding the tumor rather than in the tumor itself, the dose of treatment is related to the tumor size as well as to the isotopic properties. The main action of diphosphonates is to inhibit osteoclast activity. By binding strongly to hydroxyapatite crystals on the bone matrix, it can reach high concentrations of aggregates at the bone defects destroyed by osteoclasts, thus causing apoptosis. Currently, a variety of diphosphonates are used in the United States and Europe for the treatment of bone metastatic cancer. Oral chlorophosphates of 1600 mg/d, intravenous aminodiphosphate disodium 90 mg or zolpidem phosphate 4 mg, etc. In addition, recent studies have suggested that diphosphonates may have a direct pro-apoptotic effect on tumor cells. diphosphonates are a valuable drug in the treatment of bone metastatic cancer, and its preventive effect on tumor metastasis is currently under further evaluation.