Experts' agreement on therapy for bone metastases

Overview of bone metastases

After lung and liver, the skeleton is the third most frequent site to which malignant tumors metastasize. About 70%–80% patients with malignant tumor will eventually develop bone metastasis, the incidence being 35–40 times that of primary bone tumor, making bone metastasis a very common problem for the orthopedist.

Clinical features

Bone metastases typically present with destruction of multiple bones and have a high incidence rate in middle‐aged to elderly patients with a male‐to‐female ratio of 3:1. Spine, pelvis and the metaphyses of long bones are common locations. Frequent clinical manifestations include: (i) pain (50%–90%); (ii) pathological fracture (5%–40%); (iii) hypercalcemia (10%–20%); (iv) symptoms of spinal instability and spinal cord or nerve compression (<10%); and (v) bone marrow suppression (<10%).

Common origins for bone metastatic tumor

Cancers from breast, prostate, lung, thyroid gland, and kidney account for more than 80% of all skeletal metastases ¹ (Table 1).

Table 1.

Incidence and prognosis of common bony metastases

Primary tumor	Incidence of bone metastases (%)	Median survival (months)	Five‐year survival rate (%)
Myeloma	95–100	20	10
Breast	65–75	24	20
Prostate	65–75	40	15
Lung	30–40	<6	<5
Kidney	20–25	6	10
Thyroid gland	60	48	40
Melanoma	14–45	<6	<5

Bone metastasis from breast cancer

A high proportion (65%–75%) of patients with breast cancer develop bony metastases depends upon the fairly good prognosis. Thus a relatively aggressive treatment strategy should be adopted because patients with breast cancer have a 2‐year median survival even after the development of bony metastases.

Bone metastasis from prostate cancer

With the characteristics of osteogenic metastatic focus in a high proportion of patients and prostatic specific antigen (PSA) providing an important clinical parameter, prostate cancer also has a high incidence of bony metastases, the incidence being similar to that of breast cancer. Most patients with early‐stage prostate cancer have a favorable prognosis thanks to its hormone‐dependence.

Bone metastasis from lung cancer

Patients with lung cancer have a 30%–40% incidence of bone metastasis and a fairly poor prognosis, with an approximate one‐year survival rate of 5%.

Bone metastasis from renal cancer

Bone metastasis from renal cancer has a high incidence, 25% of patients with renal cancer developing bony metastases. Preventive internal fixation for bone metastasis from renal cancer should be adopted with a positive attitude, because metastatic foci resolve spontaneously in some of these patients after removal of the primary tumor.

Bone metastasis from thyroid carcinoma

Thyroid carcinoma is also prone to bony metastases, serious bone destruction by osteolytic lesions and a high incidence of pathological fracture occurring commonly. In patients with bone metastasis from thyroid carcinoma, pathological fractures can be prevented by preventive internal fixation and there is a favorable prognosis when such surgery is combined with postoperative internal radiation by ¹³¹I or radiotherapy.

Radiologic features

There are three types of radiographic appearance of metastatic bone lesions, namely osteolytic, osteoblastic and mixed lytic‐sclerotic. The majority have an osteolytic appearance, the bone defects having a moth‐eaten or geographical appearance with unclear boundaries, irregular margins, non‐sclerotic rims and no periosteal reaction. Punctate, flake‐like or even dentin‐like hyperdense lesions can be found in osteoblastic metastases with disordered, thickened, coarse bone trabeculae and, in some instances, an increased volume of bone. Both osteolytic and osteoblastic characteristics can be found in bony metastases of mixed lytic‐sclerotic type. The tumor size, extent of invasion and relationship to adjacent tissue or organs can be defined precisely and effectively by CT and MRI. The radionuclide bone scan is extremely significant in the diagnosis of metastatic bone disease, being an effective means of early screening of the entire skeleton for metastatic foci, however false positives must be excluded. The new technology of PET is gradually assuming a more significant role in the process of diagnosis of bony metastases.

Diagnosis

When evaluating patients with a history of primary cancer who present with bone destruction, the surgeon can assume that bony metastases are most likely to be the correct diagnosis. In addition, the location of the primary tumor can be ascertained in 22.6%–30.0% of patients with metastases of unknown origin but without a history of primary cancer (Fig. 1) ² , ³ . A prospective study of diagnostic strategy showed that primary lesions could be found in 85% of cases through a standard process of diagnosis as follows ⁴ :

Figure 1.

Diagnostic process for bone metastases.

• 1Age, medical history and tumor location: the incidence of bone metastases is much higher than that of primary bone tumors in adults aged 40 years or older and bony metastases are generally located in the proximal limbs or spine. Most bony metastases of unknown origin come from the lung or kidney, thus most of the primary foci can be found through examination of the thoracic and abdominal viscera.
• 2Physical examination: more clues may be obtained by focusing on prostate, breast, thyroid gland and abdomen.
• 3Laboratory examination: apart from PSA, alpha feto‐protein and ruling out the diagnosis of multiple myeloma, it is difficult to determine tumor origin through laboratory examination.
• 4Imaging evaluation: inspection methods include X‐ray, type‐B ultrasound and CT, which should mainly focus on the location of thoracic and abdominal viscera, while radionuclide bone scan, PET and whole body MR scan should be applied for the diagnosis of bony metastases.
• 5Pathological diagnosis: in addition to the above investigations, a definitive diagnosis can usually be made by pathology, immunohistochemistry providing more information about the primary tumor. The source of tumor cells can be identified in up to 72% patients by a combination of pathological examination and other clinical investigations.

Principles of, and indications for, preoperative biopsy

• 1Preoperative biopsy must be performed in those patients without a history of cancer who are suspected to have bony metastases. After the diagnosis of bony metastasis, a search for the primary tumor guided by the pathology findings should be undertaken.
• 2Preoperative biopsy is unnecessary for patients with a definite history of cancer who present with multiple bony destruction, including long bones, vertebral body and pelvis.
• 3For the patient with a history of cancer who presents with a solitary site of bony destruction, biopsy should be considered in preoperative planning to confirm the diagnosis. According to reports in the literature, in long‐term surviving patients with malignant tumor, almost 15% of new tissue growth in bony foci were non‐carcinoma disease or tumors which were not metastases from the known original primary tumor ⁵ .

Treatment

The goal of treatment of metastatic carcinoma is to extend life, alleviate symptoms, improve the quality of life, prevent or manage pathological fracture and decompress nerves. Comprehensive treatment should be adopted, including surgery, radiotherapy, utilization of bisphosphonates, systemic therapy for the primary tumor (systemic chemotherapy and molecular‐targeting therapy), management of pain and nutritional supporting therapy.

Principles of surgical treatment6, 7

It is still relatively difficult for the orthopaedic surgeon to decide which types of patients with bony metastases are suitable for surgical intervention, especially when it comes to preventive surgery. Some scoring systems, such as the Mirels' scoring system for long bone ⁸ and the Tomita scoring system for the spine ⁹ , have been used in the clinic. Although the use of these scoring systems may provide better guidance for surgery on bony metastases, factors such as the differential diagnosis, quality of normal bone surrounding the lesions, degree of activity, survival expectation, sensitivity to radiotherapy, and differences in comprehensive analysis of the radiological findings all influence prediction of fracture risk. The orthopaedic surgeon should be familiar with the indications for surgical intervention for bony metastases, master every type of rigid internal fixation for every part of the body, and select as appropriate either internal fixation, reconstruction after tumor resection or new minimally invasive treatments. Where a lesion has eroded adjacent joints, or internal fixation cannot provide early and full weight bearing, tumor resection followed by reconstruction by arthroplasty should be adopted. Prostheses should be fixed by bone cement in order to facilitate early recovery. The use of biological reconstruction should be minimized because patients need to wait for bone healing and undergo radiotherapy. With improvement in internal fixation of limbs and spine and the development of tumor prostheses, reconstruction has become more simple and durable and the scope of surgical management of bony metastases has widened.

Minimally invasive treatment

Minimally invasive surgery has the advantages of shorter operating time, less trauma, and low cost and often can be carried out under local anesthesia, which is especially suitable for patients with multiple bony metastases or in poor general condition.

Percutaneous vertebroplasty, kyphoplasty and osteoplasty

Percutaneous vertebroplasty and kyphoplasty have been used in the treatment of spinal metastases ¹⁰ with the purpose of maintaining or recovering the height of compressed vertebrae so as to alleviate pain and prevent fractures, and have also been combined with posterior‐instrumentation surgery to consolidate the strength of the vertebral bodies. Osteoplasty with percutaneous injection of bone cement has been applied to osteolytic lesions in other parts of the body such as the acetabulum, plugging the bone defects caused by osteolytic lesions, maintaining the stability of the skeleton and delaying the occurrence of pathological fracture. After injection of bone cement, heat, which partially kills tumor cells, is released in the process of bone cement polymerization. Osteoplasty is not recommended for patients with large cortical bone defects and tumor extending into adjacent soft tissue to an extent three or more times greater than that of the bone disease. Bone cement serves not only to strengthen the sclerotin but also to inhibit the development of local metastases when used in combination with anti‐neoplastic and anti‐bone destruction drugs.

Interventional therapy

Microwave ablation, high intensity ultrasound, laser beam and radiofrequency ablation (AFA) all possess anti‐tumor effects ¹¹ and can help to relieve symptoms when used in appropriate patients with bone metastases. Combining these modalities with other treatment approaches can effectively provide pain relief and restore ambulatory function, and is suitable for some patients with radio‐resistant tumors. There are also reports in the literature concerning cryoablation for treatment of bone metastases.

Radiotherapy

As an effective palliative treatment modality for patients with bony metastases, local radiotherapy can provide significant pain relief for 70% of patients, 40%–60% gaining complete pain relief. Symptoms can improve as soon as 48 h after radiotherapy ¹² . In one study, the complete remission rate was 81% in a conventional fraction group, 65% (P = 0.03) in a short course fraction group and 46% (P = 0.0001) in a fast course fraction group, an overall pain relief rate of 76% being achieved in the three groups ¹³ . The mechanism of action of radiotherapy is to inhibit or destroy tumor cells, prevent the invasion and destruction of bone, promote the activity of osteoblasts and accelerate collagen synthesis for new bone formation. Radiotherapy often needs to be combined with other modalities such as surgery. The application of radiotherapy alone is indicated under the following five conditions: (i) inability to tolerate surgery and a predicted survival of less than 6 months; (ii) low risk of pathological fracture; (iii) no pre‐existing obvious spinal instability or neurologic impairment; (iv) no complaints of dysfunction in patients with pelvic tumor not involving the acetabulum; and (v) radiation‐sensitive tumor.

It should be noted that radiotherapy for bony metastases cannot achieve long‐term control. A retrospective analysis of 12 randomized trials showed that the duration of pain relief is much less than the period of survival after treatment ¹⁴ .

Bisphosphonates

As strong and effective inhibitors of bone resorption, bisphosphonates are used to treat tumor‐associated osteolysis and hypercalcemia and thus to reduce the incidence of skeleton‐related events ¹⁵ . These agents accelerate apoptosis and inhibit the proliferation of both tumor cells and osteoclasts. At the same time, they also help to stimulate T cells in the immune system resulting in anti‐tumor effects. Bisphosphonates can provide pain relief, prevent pathologic fracture and prolong survival time in most patients with bone metastases from breast, prostate cancer and multiple myeloma. The third generation of bisphosphonates, such as zoledronic acid, can be effective in patients in whom other bisphosphonates have failed and strengthen anti‐bone resorption almost 1000‐fold with less adverse effect by aminating the R2 side‐chains of bisphosphonates. Bisphosphonates are suitable for patients with radiographic evidence of bone metastases (Table 2). An analysis of bisphosphonates compared with placebo for bone metastases showed that they significantly reduced the risk of fractures and hypercalcemia but not of orthopaedic surgery or spinal cord compression in studies that lasted ≥6 months ¹⁶ . Intravenous bisphosphonates significantly delayed the initial appearance of skeletal related events but did not prolong the survival time. Therefore, once bony metastases have been diagnosed, treatment with bisphosphonates should be instituted until clinical related events disappear.

Table 2.

Bisphosphonate treatment of bone metastases

Radiographic evidence of bone metastases	Bisphosphonate treatment
Osteolytic destruction on X‐ray films	90 mg pamidronate intravenous infusion in 2 h or 4 mg zoledronic acid intravenous infusion in 15 min every 3–4 weeks
Abnormal bone scan, normal X‐ray films, bone destruction on CT or MRI	Suggested
Abnormal bone scan, normal X‐ray films, no bone destruction on CT or MR	Not suggested

Management of pain

Bone metastases are a category of advanced malignant tumor. Eighty percent of patients with bone metastases complain of pain, 50% of which is severe and 30% of which is unbearable. Management of pain in patients with bony metastases includes radiotherapy, chemotherapy, palliative surgery and treatment using the three‐step analgesic ladder. Radiopharmaceutical therapy has been applied for systemic pain in recent years ¹⁷ , for example with ¹⁸⁶Re‐HEDP (rhenium), ¹⁵³Sm‐EDTMP (samarium) and ⁸⁹Sr‐chloride (strontium). These drugs accumulate in the location of bony metastases in a concentration 2–25 times that of normal bone, commonly start to work within the first week and maintain effectiveness for 1–12 months.

Surgical treatment for spinal metastases

The spinal column is the most frequent site of bony metastases, 70% of which are found at the thoracic level, 20% in the lumbar region, and 10% in the cervical region. Vertebral destruction caused by metastases can cause severe pain and compression of the spinal cord. In the past, radiation therapy was the primary therapeutic modality for spinal metastases, but a prospective randomized clinical study has shown that decompression of the spinal cord and rigid internal fixation combined with postoperative radiotherapy result in a higher ambulatory rate, better sphincter function and muscular strength and longer survival time than occurs with radiation therapy alone ¹⁸ . The addition of surgery before radiotherapy for patients with malignant spinal‐cord compression improves ambulatory function. The histologic type of the primary tumor is the strongest prognostic factor, breast cancer, prostate cancer, myeloma, thyroid cancer and renal cell cancer having better prognoses ¹⁹ . As reported in published articles, surgical treatment for spinal metastasis has proven beneficial for more than 80% of patients ²⁰ . Thus surgery should be considered when dealing with patients with better prognoses.

Indications for surgical treatment of spinal metastases

The principle of treatment of spinal metastases is palliative therapy. Thus the goal of treatment of metastatic carcinoma of the spine is to provide pain relief, maintain neurologic function and restore the structural integrity of the spinal column. A small number of cancer patients may also be cured by wide excision.

Evaluation of spinal metastases

Tokuhashi et al. have reported a scoring system consisting of six factors which are thought to affect the duration of survival for preoperative evaluation of the prognosis of metastatic spinal tumor, the maximum possible score being 12 ²¹ . The six factors include the patient's general condition, the number of extraspinal bony metastatic foci, the number of metastases in the vertebrae, metastases in the major internal organs, the primary site of the cancer, and the degree of paralysis. Using these criteria, the authors recommend excisional surgical treatment for patients with a total score of 9 or higher and palliative surgical treatment for patients who have a total score of 5 or less. Tomita and his colleagues revised the Tokuhashi score system and devised a new scoring system consisting of three items including grade of the primary tumor, visceral metastases to vital organs, and number of bone metastases ⁹ (Fig. 2). For patients with a prognostic score of 2–3 points a wide or marginal excision is suggested for long‐term local control; with 4–5 points marginal or intralesional excision is indicated for middle‐term local control; with 6–7 points palliative surgery for short‐term palliation is justified; and with 8–10 points nonsurgical supportive care is indicated.

Figure 2.

Surgical strategy for spinal metastases according to the Tomita scoring system. ECOG, Eastern Cooperative Oncology Group; exc, excision; m, months; met, metastasis; mets, metastases; P, prognostic; y, years.

At present, the Tomita score system is widely accepted as an approach to assessing the prognosis and devising a treatment strategy for patients with spinal metastases.

Surgical indication

According to most published articles and the expert consensus ²² , ²³ , ²⁴ , the following factors should also be taken into account when evaluating the prognosis of spinal metastases by the Tomita scoring system: (i) neurologic compression caused by radioresistant cancer will result in progressive impairment of neurologic function; (ii) existing or occurring spinal instability; (iii) existing severe intractable pain indicating that conservative treatment is ineffective; (iv) tumors may continue to increase in size after radiotherapy; (v) a need to confirm the pathological diagnosis; (vi) patients' survival expectancy is 3 to 6 months or longer, and their general condition is good; and (vii) bone inadequacy, compression of multiple segments of the spinal cord by tumor or a life expectancy of less than 3 months should be regarded as indications for conservative treatment. Neurologic compression and spinal instability are relatively important indications for surgery. Assessment of a combination of the Tomita scoring system with these factors can play a guiding role in choosing normative treatment for patients with spinal metastases (Fig. 3). Treatment of severe pain caused by spinal metastases is equally important and appropriate treatments depending on the pathogenesis of pain should be given (Table 3).

Figure 3.

Algorithm for management of spinal metastases.

Table 3.

Pain categories and strategies for treatment of spinal metastases

Classification of pain	Mechanism of pain	Characteristics of symptoms and signs	Strategies of treatment
Local pain	Tumor stretching of the periosteum, local inflammatory stimuli	Local ache and swelling, pain, commonly percussion pain of spinous processes	Steroidal drugs
Mechanical pain	Vertebral deformation, spinal instability	No pain at rest but pain during activity	Rigid internal fixation
Neurogenic radicular pain	Compression and stimulation of nerve roots	Symptoms in area of innervation, long tracts impairment, urinary bladder and bowel disorder	Decompression of nerve root and spinal cord

Surgical modalities for spinal metastases

Indications for laminectomy

Patients with disease affecting multiple segments, in poor medical condition and unable to tolerate major surgery may require laminectomy and decompression of the spinal canal. However, simple laminectomy cannot expose the lesion adequately and may aggravate spinal instability, and the outcome is not as good as with corpectomy. The rate of improvement in neural function is about 30% ²⁵ . Thus rigid internal fixation is necessary to reduce the incidence of neural dysfunction and pain caused by spinal instability.

Indications for corpectomy

From reviewing published articles about treatment for metastatic spinal cord compression, it has been concluded that anterior decompression provides the best results ²⁶ . Other researchers also agree that the location of the tumor determines the decompression approach. Because spinal metastases mainly corrode the vertebral body, anterior decompression can provide better results in patients who are in good medical condition, have a relatively long life expectancy, and whose disease is confined to one or two contiguous levels. Wide exposure of the anterior aspect of the spine facilitates complete resection of the tumor and decompression of the spinal cord. This must be followed by spinal reconstruction and rigid internal fixation. Using bone cement and an artificial vertebral body for vertebral reconstruction after radical tumor resection can stabilize the anterior column. Spinal fixation is limited to the levels adjacent to the affected vertebrae when using a screw and plate for surgical internal fixation.

Indications for total en bloc spondylectomy

Isolated spinal metastases with a favorable prognosis and total score of 3 or less in the Tomita scoring system should be treated like primary tumors. An anteroposterior double approach for complete resection of the tumor is commonly adopted. Complete resection of the tumor, spinal decompression, and pedicle screw fixation through a posterior approach is followed by corpectomy and internal fixation through an anterior approach. The anteroposterior double approach can be completed simultaneously or in different stages depending on the degree of trauma and amount of bleeding.

Total en bloc spondylectomy through a single posterior approach is also available and may result in better local control of the tumor. Tomita et al. reported a retrospective study of 198 spinal metastases patients from 1989 to 2003, 64 of whom underwent total en bloc spondylectomy ²⁷ . The two‐ and five‐year survival rates of patients undergoing total en bloc spondylectomy were 66.6%and 46.6%, respectively.

Indications for percutaneous vertebroplasty and kyphoplasty

Indications for these procedures include: (i) osteolytic lesions; (ii) an intact posterior vertebral body cortex; (iii) patients with severe pain caused by vertebral deformation who cannot tolerate general anesthesia and surgery; and (iv) no definite symptoms and signs of radiculopathy. Retrospective and prospective studies have all reported significant improvement in pain scores in 90% of patients undergoing percutaneous vertebroplasty and kyphoplasty, and the improvements were sustained at 1 year or longer ²⁸ . The incidence of complications for this type of operation is 5%–10% for patients with spinal metastases, which is greater than that of patients with osteoporosis and hemangioma. The major complication is cement leakage, while serious complications such as spinal cord compression and pulmonary embolism are rare ²⁹ .

Surgical treatment of long bone metastases

The long bones of the extremities are very common locations for metastatic tumors. Affected sites include the proximal femur, followed by the proximal humerus, and much less frequently, by bones distal to the knee and elbow. Of patients with bone metastases, about 10% develop pathologic fractures ³⁰ . The pathologic fracture is an important cause of death in patients with bone metastases, and orthopaedic specialists should consider both the risk of pathological fracture and expected survival time of patients when optimizing treatment measures for preventing pathologic fractures.

Prediction of risk of pathologic fracture in long bones

Detailed preoperative evaluation is required to assess the risk of fractures, including type of primary tumor, previous therapy, duration of disease, size, site and type of lesion (lytic or blastic nature), and presence of symptoms attributable to the lesion. In 1989, Mirels reviewed 38 patients with 78 metastatic lesions of long bones and published a rating system based on four variables (Table 4): site of lesion (upper limb, lower limb, and peritrochanteric); grade of pain (mild, moderate, and functional); type of lesion (lytic, blastic, and mixed); and size of lesion as a proportion of the long bone diameter (<1/3, 1/3–1/2, >2/3) ⁸ . In this system the maximum obtainable score is 12 points. The probability of fracture with a score of <7 is very small (4%). For a lesion with a score of 8, the chance of fracture is 15%. When the score reaches 9, the probability of fracture is 33%. Therefore, if a score of 9 or more is obtained, the risk of fracture warrants prophylactic fixation of the bone. The results of a study on the reproducibility, validity, and applicability among examiners of various experience levels and training backgrounds showed that the Mirels' rating system had strong reproducibility and was suitable for different categories of physicians. The individual Mirels' score component with the greatest variability was pain, followed by size, type of lesion, and site, respectively. The overall sensitivity and specificity of the applied Mirels' system were 91% and 35%, respectively, which meant that 2/3 of patients underwent unnecessary procedures to prevent fractures ³¹ . While strict application of the Mirels' rating system may lead to a certain degree of over‐treatment, once a pathologic fracture has occurred, the consequences are even more serious.

Table 4.

Mirels' scoring system for risk of pathological fracture of long bones

Variable	Score
	1	2	3
Site	Upper limb	Lower limb	Peritrochanteric
Pain	Mild	Moderate	Severe
Lesion	Blastic	Mixed	Lytic
Size*	<1/3	1/3 to 2/3	>2/3

^* Proportion of shaft diameter.

Indications for surgery in long bones metastases

In addition to the Mirels' rating system, other factors which should be comprehensively considered include: (i) whether the overall condition of the patient is good enough, and the length of expected survival is more than 12 weeks; (ii) whether the patient can benefit from surgical treatment (the procedure should allow for early mobilization and facilitation of nursing); (iii) solitary metastasis, primary tumor has been completely removed or can be cured; (iv) patients with actual or high risk of pathological fractures, Mirels' score > 9 points, X‐ray films showing that the lesion occupies 50% of the bone diameter, measures at least 2.5 cm, and is accompanied by destruction of the lesser trochanter of the femur; and (v) patients for whom radiation therapy has failed and who have persistent pain without relief.

Surgical principles in patients with long bones metastases

The goal of surgical management is to prevent pathologic fracture or reconstruct continuity of fractured bone. Much attention should be paid to minimizing damage to soft tissue around the bone; providing the most effective fixation methods enables the patient to derive the most benefit in terms of rapid postoperative recovery of limb function. Where destruction is not serious, the use of a closed intramedullary nail could be considered; whereas when destruction is extensive, the lesion should be removed, followed by application of cement filling and internal fixation. A replacement prosthesis should be reserved for cases where bone destruction caused by a metastatic lesion is severe and may result in functional impairment. Before surgical intervention is undertaken on highly vascular lesions, preoperative vascular embolization is recommended; much attention should be paid to reducing the trauma and mortality of surgery.

Surgical procedures for long bones metastases

Long bones of the upper extremities

20% of bone metastases are upper extremity and scapula lesions, the humerus being involved in 50% of these cases. The classic criterion for an impending pathologic fracture in the upper limbs is commonly cited as a lesion that occupies more than 75% of the bone diameter, but we suggest that the criteria should be much stricter.

• 1Proximal humerus: Bone cement filling and plating, or partial shoulder replacement, can be considered according to the size of the lesion. Patients with a longer expected survival time are possible candidates for allograft prosthetic composite (APC). Attention should be paid to immobilizing the limb to prevent migration or dislocation of the prosthesis after surgical management; to salvaging the deltoid, axillary nerve and rotator cuff; and to cementing the prosthesis into the proper position. Postoperatively, patients should be prevented from moving the affected limb by keeping a triangular bandage sling in place for 6–8weeks.
• 2Humeral diaphysis: The suggested treatment of diaphyseal metastatic lesions is with open or closed locked intramedullary nails. The extent of fixation is from the surgical neck to 5–6 cm above the humeral condyle and this can be augmented with cement. The internal fixation should be sufficiently stable. If humeral fracture has already occurred or fixation with a locked nail is not firm, external fixators or aids can be used to support the stabilization postoperatively. During the procedure of closed intramedullary nailing, a biopsy specimen from the bone metastasis can be obtained through the nailing hole for histopathologic examination. Another option available for humeral fixation is cementing and plating. There is no significant difference between intramedullary nailing and plating in outcome, but fixation by plating requires better bone quality, a more extensive surgical approach, and is accompanied by greater trauma to the patients ³² . Where bone destruction has resulted in a defect of 3–4 cm or less, the surgeon can shorten the humerus after resecting a middle segmental lesion. Where bone destruction is too extensive and has resulted in an incomplete cortex, an intercalary prosthesis can be used for the treatment of segmental defects of the humeral diaphysis, allowing preservation of the proximal and distal humeral articular surface ³³ , ³⁴ .
• 3Distal humerus and the region near the elbow: Lesions of the distal humerus may preclude the use of intramedullary nailing. In such cases, plating and cement fixation are more appropriate alternatives. Much attention should be paid to avoiding destruction of the olecranon during the operation as postoperative radiotherapy can easily lead to occurrence of bony nonunion. Where the lesion is extensive and/or needs to be resected completely, elbow arthroplasty should be performed after resection ³⁵ . Total elbow arthroplasty can be used to reconstruct the articular surface of the distal humerus and the bone defect. It is uncommon to perform joint replacement when dealing with patients who have a distal humeral lesion. The operation is usually performed through a posterior longitudinal approach. Much attention should be paid to retaining the medial and lateral condyles of the humerus in order to restore the functions of extension and flexion.
• 4Ulna and radius: Metastases to the ulna and radius are very rare, but most cases require surgical treatment because the ulna and radius are always under a torque load during the movements of pronation and supination, which can easily result in pathologic fracture. We therefore recommend internal fixation to prevent fracture in patients with ulnar and radial metastases. Internal fixation mainly involves plating combined with packing of the defect with bone cement. When bone destruction is very serious, the surgeon can perform a tumor segment resection. Total elbow arthroplasty is the treatment for elbow surface destruction caused by an ulnar lesion. When radial metastatic involvement is focused on the wrist, the radial defect is reconstructed with an autograft from the fibula. An exclusion operation could be used after tumor resection of other sites.
• 5Shoulder‐girdle: Scapula and clavicle are also common locations for bone metastases. Generally speaking, surgical treatment is unnecessary unless pathological fracture has occurred and the shoulder has been involved by the lesion. Radiation therapy remains the primary therapeutic modality for the treatment of metastases to the shoulder girdle. Where the humeral head and neck are involved by a lesion surrounding the shoulder, hemiarthroplasty is the reconstructive procedure of choice. The method of plating and cementing can be used for the treatment of clavicular fracture. Patients with radiation‐resistant tumor or severe pain can undergo local resection of the lesion.

Long bones of the lower extremities

• 1Femoral head and neck: Patients with actual or impending pathologic fracture of the femoral head and neck are best treated with cemented hemi‐arthroplasty rather than internal fixation, because of the high likelihood of fixation failure ³⁶ . Three types of stem are available; namely short, middle‐length, and long stems. The whole femur should be examined carefully in order to detect distal lesions. When distal lesions are present, a long stem prosthesis should be used to accommodate them. Even where no identifiable concurrent lesions are present, a long stem should be considered in order to decrease the risk of pathologic fracture of the femur during the patient's remaining lifespan. However, the use of long stem does seem to carry an increased risk of pulmonary embolism and cardiac arrest. Appropriate surgical and anesthetic measures should be taken to minimize these risks ³⁷ .
• 2Intertrochanteric region: Internal fixation of pathologic intertrochanteric fractures has traditionally employed a dynamic hip screw (DHS) combined with curettage and packing of the defect with bone cement. Preservation of the patient's own articular surface is a purported advantage of this technique. One problem with DHS fixation is the inability to address distal impending fractures or to protect the distal femur prophylactically from progression of metastatic deposits. Based on these considerations, an intramedullary fixation device might be a good option for management. Closed or open intramedullary nailing combined with cementing could be considered. Arthroplasty might be used for patients with severe bone destruction in order to facilitate restoration of limb length and joint stability. Calcar replacement arthroplasty allows modular replacement of diseased medial bone down to healthy, uninvolved bone at, or above, the distal aspect of the lesser trochanter. Insufficient bone in the greater trochanter and/or subtrochanteric region warrants consideration of proximal femoral replacement prosthesis. With these two prostheses, hemi‐arthroplasty is preferred over total hip arthroplasty in order to preserve inherent joint stability. Both of the two prostheses are available in standard and long‐stem lengths to address distal lesions. Cementing of these stems in the treatment of pathologic disease is strongly recommended because non cemented prostheses are unreliable. Survivorship of these prostheses is excellent over the shortened lifespan of these patients.
• 3Subtrochanteric region: Options for the treatment of subtrochanteric pathologic fracture include intramedullary nails and proximal femoral prosthetic replacement. From a biomechanical point of view, forces measured in the subtrochanteric region are the greatest of any long‐bone site in the body and can reach six times body weight. In the setting of pathologic fracture, where healing of bone is very difficult, standard subtrochanteric fixation devices such as the rigid blade plate and dynamic condylar screw have an unacceptably high incidence of failure. Intramedullary nails have become the standard implant for this level of fracture or impending fracture. Proximal femoral replacement prostheses should be reserved for either of the following two situations in the setting of metastatic disease. First, they should be used when the proximal femoral bone is so severely destroyed by a metastatic lesion that neither internal fixation nor femoral calcar replacement prosthesis is appropriate. In most cases, the extent of such bone destruction will extend from the femoral neck and/or head region to a level at, or below, the subtrochanteric region. However, disadvantages of proximal femoral replacement prostheses include greater cost and trauma, and more complications.
• 4Femoral diaphysis: The most common method has been the use of locked intramedullary nails. In particular, a reconstruction‐type intramedullary nail is favored because it can protect the femoral neck prophylactically. The indications and surgical procedure for using locked intramedullary nails are the same as those for subtrochanteric lesions. When a segmental bone defect is present, the following options can be selected: (i) shortening the femur and inserting an intramedullary nail (only for very short segments); (ii) applying cement to bridge the segment around the nail; (iii) applying a proximal femoral replacement prosthesis (must have adequate distal bone for cementing the implant intramedullary stem); (iv) applying an intercalary metal spacer (must have adequate remaining proximal and distal femoral canals for cementing of the intramedullary stems of the intercalary implant). A retrograde femoral nail may be indicated when the patient has had a prior hip arthroplasty.
• 5Femoral supracondylar region: If the bone is not severely destroyed by a metastatic lesion, a condylar plate combined with curettage and packing of the defect with bone cement can be used. A knee arthroplasty is indicated when the knee surface has been severely destroyed, in order to provide early stability and good function. A retrograde nail only should be inserted when both the femoral condyle and diaphysis are involved by metastatic lesions.
• 6Tibia: The tibia accounts for fewer than 5% of metastatic bone tumors. Knee arthroplasty can be performed when the joint surface is affected by a pathologic fracture of the tibial plateau. The appropriate treatment for tibial diaphyseal lesions is insertion of intramedullary nails combined with curettage and packing of the defect with bone cement. Much attention should be paid to local soft tissue conditions in order to avoid wound complications.

Surgical treatment for metastatic carcinoma of the pelvis

About 10%–15% of bony metastases are found in the pelvis, most being located in the periacetabular region. Significant pain and disability caused by metastatic carcinoma of the pelvis can seriously affect the quality of patients' lives. Surgery in this region is difficult and risky, thus preoperative evaluation and designing of the operation are of vital importance.

Subareas of metastatic carcinoma of the pelvis

Enneking and Dunham have classified pelvic metastases as follows: area I (ilium), area II (periacetabular tumor), area III (pubic and ischial lesions) and area IV (iliac lesions involving the sacrum) ³⁸ . In addition to the location of the tumor, the patient's general condition and symptoms, biological behavior of the primary tumor, tumor size and influence on function all play significant roles in determining optimal treatment of pelvic metastases. Because tumors located in areas I, III and IV generally have no impact on the patient's weight‐bearing, conservative treatment is the treatment of choice except when complete, tumor resection with curative intent is considered possible ³⁹ . Metastatic tumor located in area II does have an impact on the patient's weight‐bearing and surgical treatment is always needed.

Surgical management of pelvic metastases

Surgical management of pelvic metastases mainly consists of curettage and bone cement implantation, but for isolated and radioresistant bony metastatic foci with good prognoses, wide excision is needed. Semi‐pelvic amputation is required when nerve and blood vessels are invaded by huge tumors. The goals of surgical treatment for pelvic metastases include: (i) maximum excision of tumor, adequate reconstruction of the defect in the pelvis and prevention of pathologic fracture; (ii) pain relief through removal of tumor lesions; (iii) improvement in function and quality of life; and (iv) clarification of the diagnosis in order to plan comprehensive treatment.

Periacetabular metastases

Metastases involving the acetabulum are often treated by surgery in order to excise the tumor, implant the defect caused by it and reconstruct hip joint function. Radiotherapy can cause degeneration and necrosis of the cartilage surrounding the femoral head and hip joint, resulting in pain after activity and increasing the risk of central dislocation of the hip joint. According to the patient's condition, surgical treatment is recommended under the following three conditions: (a) severe symptoms which are not alleviated by immobilization of the limb, analgesic drugs and anti‐tumor therapy; (b) no pain relief or unsatisfactory recovery of function of the affected extremity after radiotherapy; and (c) pathologic fracture of the ipsilateral femur or adjacent site requiring simultaneous treatment.

Harrington classifies periacetabular metastases into four types according to the acetabular location of tumor involvement ⁴⁰ . The appropriate surgical measures depend on the location of tumor involvement. Type I defects classically demonstrate acetabular articular surface lesions, intact lateral cortices and structurally intact superior and medial walls and are typically managed with a standard cemented total hip arthroplasty procedure. Type II defects lack the medial wall of the acetabulum, but the remainder of the acetabulum and supra‐acetabular region are intact. The acetabular prostheses commonly used can cause both prosthesis and bone cement to shift to the medial wall at an early postoperative stage. These defects are most appropriately managed with a cemented total hip arthroplasty with acetabular cup with mesh wings to transfer stress to the acetabular rim. Type III lesions are those in which the medial and superior walls and lateral cortices of the acetabulum are deficient. Treatment of these lesions requires a combination of Steinmann pin to transfer the stress from acetabulum to spinal column and the use of bone cement implant, acetabular cup with mesh wings and cemented total hip arthroplasty for pelvic reconstruction. Type IV lesions are isolated periacetabular lesions and require complete resection and pelvic reconstruction. Research adopting the Harrington's system of classification has found that limb function is maintained or restored and symptoms alleviated in most cases, but with some complications ⁴¹ , ⁴² .

Ilium and sacroiliac joint

Involvement of the posterior and medial part of ilium (responsible for stress transfer between acetabulum and sacrum) by tumor is an indication for surgery. Difficulty in walking and aggravation of pain by activity are commonly caused by tumor involvement of this region. Complications such as unequal length of lower extremities and separation of the pubic symphysis are observed in patients who have not undergone reconstruction after tumor resection. Consequently, suitable methods for reconstruction of pelvic integrity should be applied. The most commonly used methods are to reconstruct the connection between residual bone above the acetabulum and sacrum by Steinmann pin and reinforce it by bone cement. Tumor resection results in obvious lack of cancellous bone when tumor has involved the adjacent sacral ala. In this situation, connecting the lumbar and residual bone above the acetabulum by pedicle internal fixators and reinforcing them with bone cement can be performed. Biological reconstruction is not usually adopted for bone metastatic tumor. Hemipelvectomy is indicated when soft tissue, nerve and blood vessels are seriously involved.

Internal fixation is unnecessary for metastatic tumor of the sacroiliac joint region with mild and asymptomatic destruction, while it is necessary for patients with severe destruction, displacement, instability and pain. A Steinmann pin through the sacroiliac joint or percutaneous cannulated screw internal fixation can be used to reinforce the sacroiliac joint ⁴³ .

Pubis and ischium

Metastatic tumors of the pubis and ischium have little influence on weight‐loading and non‐operative treatment is often adopted. However, for isolated foci in the pubis and ischium, surgery treatment is usually undertaken. Bony reconstruction is not needed after simple excision of area III because the mechanical transmission mechanism between femur and sacrum still exists. However, soft tissue reconstruction is important as damage to the pelvic floor structures may result in visceral hernias.

Minimally invasive treatment for pelvic metastases

Minimally invasive techniques commonly used for pelvic metastases include radiofrequency ablation and percutaneous osteoplasty. Under CT guidance, radiofrequency ablation can be precisely directed at the location of tumors which require destruction, without having to remove them and can be carried out under local anesthesia. It is therefore especially suitable for aged patients, patients with extensive tumor involvement and patients with other serious complications. Percutaneous osteoplasty for periacetabular osteolytic metastases can instantly and effectively relieve pain, eliminate bone defects caused by osteolytic lesions, maintain stability of the pelvis and delay occurrence of pathological fractures. Some tumor cells can be killed by the heat released during polymerization after injection of bone cement. After polymerization, bone cement can also be plugged into bone defects and increase bone strength.

Disclosure

The authors did not receive any outside funding or grants in support of research for, or preparation of, this work. Neither they nor any member of their immediate families received payments or other benefits nor a commitment or agreement from a commercial entity to provide such benefits.