BACKGROUND

 

 

The skeleton, after the lungs and liver, is the third most common site of metastatic disease.4,11 Prostate,

breast, lung, kidney, and thyroid cancers account for 80% of skeletal metastases.4,11 The prolonged survival with disease of more cancer patients has led to continuously growing numbers of patients with metastatic bone disease (MBD). The exact incidence of bone metastases is unknown, but it is estimated that in the

United States alone, 350,000 people die with bone metastases from primary carcinomas.13

 

MBD is a major factor contributing to deterioration of the quality of life in patients with cancer. These patients may require surgical intervention for the management of impending or present pathologic fracture or for the alleviation of intractable pain associated with a locally progressive lesion. Those skeletal crises are associated with a considerable loss of function, pain, and the associated impairment of quality of life. Surgery may also be performed to remove a solitary bone metastasis with the intent of improving long-term survival in selected

patients,1,9 but other than this rare exception, these surgical interventions are mainly palliative and aimed at achieving local tumor control, structural stability of the surgically treated site, and restoration of normal function as quickly as possible. Failure to achieve one of these goals usually necessitates a second surgical intervention, and this is associated with additional impairment of an already compromised quality of life.

Reports show failure rates of surgeries done for MBD as high as 40% and occurring as the result of a poor initial fixation, improper implant selection, and progression of disease in the operative field.3,8,14,15

 

An attempt to treat a pathologic fracture as one would treat a traumatic fracture will fail in most cases because the underlying disease impedes the fracture healing process. The prognosis for union of a pathologic fracture is also determined to some extent by the tumor type: Those associated with metastatic adenocarcinomas of breast and prostate, multiple myeloma, and lymphoma successfully unite far more frequently than do those

associated with malignancies of the lung, kidney, and gastrointestinal tract.5,6,7 Even when healing does occur, it does so after an unreasonably long period of time and is of a less than satisfactory quality. Reduction and immobilization used in the management of traumatic fractures are, therefore, not applicable in the management of pathologic fractures due to MBD.

 

 

Gainor and Buchert5 analyzed 129 pathologic fractures and found that the long bone fractures that healed most predictably were those which had been internally fixed and irradiated and were in patients who

survived for more than 6 months postoperatively. Similar observations were made by Harrington et al.7

 

Cemented hardware or prostheses are preferentially used for fixation to achieve immediate stability, and reconstruction techniques that rely on a biologic process of bone healing (such as autologous bone grafts, allografts, or allografts prosthetic composites) are inappropriate for the surgical management of MBD.2,6,7,10

 

INDICATIONS

 

Existing pathologic fracture Impending pathologic fracture

Intractable pain associated with locally progressive disease that had shown inadequate response to narcotics and preoperative radiation therapy

Solitary bone metastasis in selected tumor types

It is agreed that surgical intervention for MBD is appropriate for patients who are expected to survive longer than 3 months. Patients who are expected to survive less than 3 months are less likely to benefit from an operation because they usually do not have the physical strength required for rehabilitation or the time needed for its completion. Those patients are treated with nonoperative approaches, such as sling and arm brace for the upper extremities or protected weight bearing for the lower extremities.

 

 

PREOPERATIVE EVALUATION

 

Although planned surgery for patients with MBD should not be delayed, preoperative evaluation and staging must not be compromised but rather thoroughly mapped out. This evaluation allows the understanding of the morphology of the lesion and its relation to adjacent structures, determining the overall skeletal staging of the patient, and detecting any other metastases that may require simultaneous surgery.

 

Because most patients who present with skeletal metastases have an established diagnosis of cancer, clinical and radiologic evaluations are usually aimed at evaluating the extent of the disease and the presence of its complications rather than at identifying its site of origin.

 

Patient History and Physical Findings

 

Medical history should include current oncologic status and related treatments and medications. It is crucial to question the patient and/or family members about his or her overall functional status and, specifically, about the status of the

 

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affected extremity prior to the occurrence of the metastatic lesion.

 

 

For example, a surgeon would be justifiably reluctant to perform major surgery on a lower extremity in a patient who was bedridden or wheelchair-bound, given that stabilization of the extremity for greater ease in maintaining pain-free personal hygiene in that patient would require a less extensive procedure. The orthopaedic surgeon should also inform the responsible medical oncologist of the impending operation, verify the oncologic information given to him or her, and be provided with the patient's estimated life expectancy.

 

The physical examination should include evaluation of the principal symptomatic area as well as other symptomatic sites. Examination should focus on the extent of soft tissue tumor extension and its relation to the neurovascular bundle of the extremity, muscle strength and range of motion of the adjacent joints, neurovascular status of the affected extremity, and limb edema.

 

Laboratory Studies

 

A complete blood count and blood chemistries should be ordered. Of specific concern in those studies is the calcium level because hypercalcemia may be a life-threatening complication of MBD. Acquiring an ionized calcium level is helpful in the diagnosis of hypercalcemia because low albumin levels may lower total calcium levels. Hypercalcemia should be treated prior to any surgical intervention. Levels of specific tumor markers should be evaluated if applicable to the specific tumor type.

Imaging Studies

 

Plain radiographs and computed tomography (CT) of the affected site should be done as well as plain radiographs of any additional site in which the patient reports of a joint or bone pain. The combined results of these studies will define the extent of bone destruction and soft tissue extension (FIG 1). If the investigated metastasis is located in a long bone, plain radiographs of reasonable quality of its entire extent should also be done to exclude additional metastases because these data are crucial for surgical planning: Missed metastases could cause pathologic fractures upon weight bearing postoperatively and require an extensive surgery for their repair (FIG 2).

 

 

 

 

FIG 1 • A. Plain radiograph showing a metastatic tumor of the right acetabulum in a 72-year-old male with a known history of thyroid carcinoma. B. CT scan shows an extensive bone destruction and soft tissue extension. Attempt at resection based on the radiographic findings alone would probably result in intralesional debulking and potential exsanguination due to the extensive vascularity of this tumor. Given these radiologic findings, this patient underwent preoperative angiographic embolization that diminished blood loss in surgery and allowed successful resection.

 

 

A total body bone scintigraphic evaluation using technetium 99m methylene diphosphonate (99mTc MDP) should be done prior to any surgical intervention: It provides information for entire skeletal staging for additional metastases as well as the means to detect metastases that may require simultaneous surgery. Bone scanning is highly sensitive for bone pathology.

 

Tracer uptake, however, is not specific for MBD and may spuriously display a large variety of inflammatory, infectious, posttraumatic, and other benign conditions. Therefore, plain radiography of any positive site on bone scan should also be done. It should be borne in mind that bone scanning is not a substitute for plain radiographs of the entire affected bone or other sites with bone pain because some tumors (such as multiple

myeloma, metastatic melanoma, and thyroid carcinoma) may not show up on a bone scan (FIG 3).

 

Chest radiographs should also be routinely done as a screening study to rule out lung metastases, considering that the lungs may be involved in the majority of common cancers. Table 1 summarizes the list of recommended studies for patients with bone metastases whose primary site of disease is unknown.

 

Impending Pathologic Fractures

 

Patients with MBD who have a pathologic fracture experience a sudden onset of debilitating pain and loss of function. They require urgent hospitalization, and this may interrupt the course of an ongoing oncologic treatment. Surgery for these fractures is frequently complicated by the presence of a substantial hematoma, soft tissue edema, and difficulties

 

 

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in obtaining appropriate reduction and alignment because of extensive bone destruction. For these reasons, it is important to identify those metastatic bone lesions that are likely to cause a pathologic fracture (ie, “impending” pathologic fractures) and to stabilize them prophylactically.

 

 

 

FIG 2 • A. Plain radiograph showing a pathologic hip fracture in a 69-year-old female with a known history of breast cancer. Hip hemiarthroplasty was performed within 24 hours of fracture occurrence (B), but postoperative radiographs showed an additional metastasis just below the tip of the prosthetic stem (C) that was missed because of the poor quality of the preoperative radiographs and because whole bone radiographs were not done before surgery. D. While she was still in hospital, she suffered a pathologic fracture through that lesion as she was being shifted from her bed to a reclining chair.

 

 

 

 

 

FIG 3 • A. Plain radiograph showing a pathologic fracture of the proximal femur in a 59-year-old female with multiple myeloma. B. Bone scintigraphy revealed no additional bone lesion, and she was treated with open reduction (without tumor removal) and uncemented internal fixation. She reported unrelenting ipsilateral knee pain and was clinically diagnosed as having degenerative joint disease and associated pain. (continued)

 

 

 

FIG 3 • (continued) C,D. Two weeks after the reduction surgery, she reported an acute onset of severe knee pain and swelling upon weight bearing: A pathologic fracture of the distal femur was demonstrated on plain radiographs. E. This patient underwent total femur resection with endoprosthetic reconstruction.

 

 

Although there is a consensus that impending fractures require prophylactic fixation, there are numerous reports describing varying concepts and methods of evaluation of these lesions as well as criteria for defining them. The agreed to and most commonly used criteria include a lytic bone lesion that measures 2.5 cm, causes circumferential destruction of 50% or more of the adjacent cortical bone, and is associated with increasing pain on weight bearing which has not responded to treatment with radiation therapy.

 

Table 1 Studies Required for the Preliminary Evaluation of a Patient with a Metastatic Disease with an Undetermined Primary Site of Disease

Physical Focus on evaluation of skin, lymphadenopathy, breast, thyroid, prostate, rectal

examination examination

Laboratory

studies

Complete blood count, blood chemistries, liver function tests, erythrocyte

sedimentation rate, serum and urine protein electrophoresis, prostate-specific antigen, urinalysis, and stool guaiac study

Imaging

studies

CT of chest, abdomen, and pelvis

 

 

Because of the complex anatomy of the acetabulum, a simple definition of impending or pathologic fracture is neither possible nor useful for planning surgical reconstruction at those sites. Instead, the location and extent

of cortical destruction are used to evaluate the biomechanical impact on function (FIGS 4,5 and 6).6,7,12

 

Biopsy

 

The mere presence of a bone lesion with a presumed diagnosis of metastasis does not mandate a biopsy. Such a lesion in a patient with an established history of malignancy and with radiologic evidence of other bone metastases does not require a biopsy prior to surgical intervention.

 

A solitary bone metastasis in a patient with a known history of malignancy or a lesion with atypical radiologic or clinical manifestations, even in the presence of other bone metastases, must be biopsied prior to any intervention.

 

 

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FIG 4 • A bone lesion measuring greater than 2.5 cm, occupying more than 50% of the cortical diameter, and associated with pain on weight bearing is considered as being an impending pathologic fracture.

 

 

 

FIG 5 • Metastatic breast carcinoma of the proximal femur in a 59-year-old patient. The lesion was asymptomatic and had been noted on a follow-up bone scan that showed increased uptake at that site. The lesion was greater than 2.5 cm, but because it had a sclerotic rim, occupied less than 50% of the cortical diameter at that region, and did not reach the cortices to violate their integrity, it did not require surgical intervention and the patient was successfully treated with radiation therapy and bisphosphonates.

 

 

 

FIG 6 • Plain radiograph (A) showing a large metastasis occupying the entire proximal femoral metaphysis (B) and metastatic lung carcinoma of the femoral diaphysis in a 70-year-old male, both symptomatic upon weight bearing and both evidencing a large lytic lesion occupying more than 50% of the cortical diameter with cortical destruction ranging from endosteal scalloping to frank breakthrough. Both lesions required prophylactic surgical intervention. C. CT scan showing an impending fracture of the left acetabulum. The femoral head is facing a large lytic lesion, occupying the entire acetabular cavity. The mechanical support to the joint is provided only by the thin layer of the remaining articular cartilage.

 

 

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FIG 7 • A. Plain radiograph showing metastatic renal cell carcinoma of the distal femoral diaphysis. This patient was treated with closed (ie, without tumor exposure and removal) retrograde intramedullary nailing and referred to postoperative radiation therapy. B,C. Radiographs taken 3 months after surgery show considerable local tumor progression that required additional and extensive surgical intervention.

 

PRINCIPLES OF SURGERY

 

The primary goals of surgery for MBD are to achieve local tumor control and structural stability of the surgically treated site. Surgery has no effect on the overall progression of disease or on patient survival. Most failures of these surgeries are attributed to inadequate tumor removal and improper reconstruction. It should be emphasized that radiation therapy is most effective when applied to microscopic disease and that it is considerably less effective when applied to large tumor volume. Surgeries done for impending or present pathologic fractures should, therefore, follow identical steps: first, removal of the tumor, and only then, reconstruction (FIG 7).

 

The decision to perform intralesional tumor removal or proceed with a resection of the affected bone segment depends on the local extent of bone loss and proximity to the adjacent joint (FIGS 8,9,10 and 11).

 

Because bone metastases usually have less soft tissue extension than primary sarcomas of bone, resection of bone metastases usually does not require en bloc removal of the surrounding soft tissues (FIG 12).

 

 

 

Reconstruction must provide immediate stability that must not rely on biologic healing processes. Therefore, the use of autologous bone grafts, allografts, or allograft prosthetic composites is inappropriate in surgery for MBD. Similarly, cementless prosthetic implants have no place in this setting. Reconstruction should include the combined use of hardware/prosthetic implants and bone cement (polymethylmethacrylate [PMMA]). The latter is used to reinforce the hardware by increasing the diameter of the construct through which the mechanical load is transmitted and improving its attachment to the neighboring bone, thereby allowing the construct to withstand the mechanical stresses of immediate weight bearing and function. Stiffness and

 

strength are related to the diameter of the intramedullary construct: The amount of stiffness in the act of

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bending is proportional to the diameter raised to the fourth power, and the strength in bending varies with the third power of the diameter (FIGS 13,14 and 15).

 

 

 

FIG 8 • A metastatic lesion of the proximal femur. Lesions such as this that do not extend to the head may be treated with intralesional tumor removal and reconstruction with cemented intramedullary nailing. On the other hand, lesions that cause extensive destruction of the femoral head may require proximal femur resection and reconstruction with cemented prosthetic implant.

 

 

 

FIG 9 • A. A metastatic lesion of the femoral diaphysis. Lesions such as this that have enough residual cortex to allow continuity may be treated with intralesional tumor removal and reconstruction with cemented intramedullary nailing. B. On the other hand, lesions that have caused extensive destruction and violated that continuity require intercalary resection of the femoral diaphysis.

 

 

 

FIG 10 • Plain radiographs (A,B) and CT scan (C) showing multiple myeloma involving the distal femur with extensive bone destruction. D. Most of the cortical diameter was destroyed and even the remaining posterior cortex had been infiltrated and thinned by the disease, and so distal femur resection with endoprosthetic reconstruction was carried out. E. The surgical specimen.

 

 

 

FIG 11 • Extensive and destructive metastasis of proximal femur which leaves no option but resection of the proximal femur and reconstruction with prosthesis.

 

REHABILITATION

 

Full weight bearing and passive and active range-of-motion exercises of the adjacent joints should be practiced as soon as possible upon wound healing and patient ability.

 

ADJUVANT RADIATION THERAPY

 

Postoperative external beam radiation therapy of 3000 to 3500 Gy is routinely administered to the entire surgical field to control remaining microscopic disease. That dose of radiation does not impede callus formation if it is feasible, as determined by underlying fracture characteristics and the patient's overall

status.5,6,7 Radiation treatment is given to the patients upon healing of the surgical wound, usually 3 to 4 weeks after surgery.

 

 

 

FIG 12 • A. Primary bone sarcomas usually have considerable extension into the soft tissues. Resection of such tumor at the proximal humerus would require en bloc removal of the overlying deltoid muscle, rotator cuff tendons, and the joint capsule. B. Bone metastases, however, usually present with less soft tissue involvement, and their resection involves removal of bony elements with only a thin layer of surrounding soft tissues.

 

 

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FIG 13 • A metastatic bone lesion treated by a closed nailing. A. This procedure is simple to perform, but it may fail because tumor progression leaves the nail as the only load-transmitting component of the lower extremity, and this ultimately results in hardware failure and breakage. B. Plain radiograph showing an impending fracture of the femoral diaphysis due to multiple myeloma. Tumor removal, cemented nailing, and postoperative radiation would most likely have resulted in local tumor control and durable reconstruction. C. Closed nailing was done in

this patient, however, and tumor progression (despite radiation) resulted in unavoidable hardware breakage. D.

Similar outcome of uncemented fixation of metastatic renal cell carcinoma of the subtrochanteric region.

 

 

 

 

 

FIG 14 • Subtrochanteric fracture following intercalary resection of a diaphyseal femoral metastasis. The use of a thin intramedullary nail, minimal cuff of cement, and supporting side plate were unable to withstand the axial forces of mechanical load. It is likely that the combination of a thick intramedullary nail and thicker cuff of cement would have prevented this fracture.

 

 

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FIG 15 • A. Surgery should include meticulous tumor removal and filling of the entire tumor cavity with bone cement. Plain radiograph showing renal cell carcinoma (RCC) metastasis to the proximal femur treated with only partial removal and cemented intramedullary fixation (B). RCCs are commonly unresponsive to radiation therapy, and the remaining tumor in this patient progressed and resulted in hardware failure at the hardware-cement interface.

 

PEARLS AND PITFALLS

History and physical ▪ Obtain data regarding pre-MBD functional status.

examination ▪ Consult the patient's medical oncologist for current oncologic status and estimated survival.

 

Laboratory studies ▪ General assessment, rule out hypercalcemia

Imaging studies

• Plain radiographs of the entire affected bone

• Total body bone scan prior to surgical intervention

• Evidence of painful lytic long bone metastasis >2.5 cm diameter, occupying >50% of the cortical diameter defines an impending fracture that requires prophylactic surgical intervention.

Surgical technique ▪ Tumor resection is done first.

• Reconstruction should include cemented internal fixation; biologic reconstruction is inappropriate.

Postoperative

treatment

• Immediate weight bearing and range-of-motion exercises

• External beam radiation therapy

 

 

REFERENCES

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2. Bickels J, Kollender Y, Wittig JC, et al. Function after resection of humeral metastases. Analysis of 59

   consecutive patients. Clin Orthop Relat Res 2005;437:201-208.

    

    

3. Dijstra S, Wiggers T, van Geel BN, et al. Impending and actual pathological fractures in patients with bone metastases of the long bones. A retrospective study of 233 surgically treated fractures. Eur J Surg 1994;160(10):535-542.

    

    

4. Dorfman HD. Metastatic tumors in bone. In: Dorfman HD, Czerniak B, eds. Bone Tumors. St. Louis: Mosby, 1998:1009-1040.

    

    

5. Gainor BJ, Buchert P. Fracture healing in metastatic bone disease. Clin Orthop Relat Res 1983;178:297-302.

    

    

6. Harrington KD. Impending pathologic fractures from metastatic malignancy: evaluation and management. Instr Course Lect 1986;35:357-381.

    

    

7. Harrington KD, Sim FH, Enis JE, et al. Methylmethacrylate as an adjunct in internal fixation of pathological fractures. J Bone Joint Surg 1976;58(A):1047-1055.

    

    

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10. Kollender Y, Bickels J, Price WM, et al. Metastatic renal cell carcinoma of bone. Indications and techniques of surgical intervention. J Urol 2000;164:1505-1508.

     

     

11. Manoso MW, Healey JH. Metastatic cancer to the bone. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology, ed 7. Philadelphia: Lippincott Williams & Wilkins, 2005:2368-2380.

     

     

12. Mirels H. Metastatic disease in long bones: a proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res 1989;249:256-264.

     

     

13. Roodman DG. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655-1664.

     

     

14. Wedin R, Bauer HC. Surgical treatment of skeletal metastatic lesions of the proximal femur: endoprosthesis or reconstruction nail? J Bone Joint Surg Br 2005;87(12):1653-1657.

     

     

15. Yawaza Y, Frassica FJ, Chao EY, et al. Metastatic bone disease. A study of the surgical treatment of 166 pathological humeral and femoral fractures. Clin Orthop Relat Res 1990;251:213-219.