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2009;91:1503-1516. doi:10.2106/JBJS.H.00175 J Bone Joint Surg Am.Jacob Bickels, Shlomo Dadia and Zvi Lidar

Surgical Management of Metastatic Bone Disease

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Current Concepts Review

Surgical Management of MetastaticBone Disease

By Jacob Bickels, MD, Shlomo Dadia, MD, and Zvi Lidar, MD

Investigation performed at the Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel

� Metastatic bone disease is a major contributor to the deterioration of the quality of life of patients with cancer; itcauses pain, impending and actual pathological fractures, and loss of function and may also be associated withconsiderable metabolic alterations.

� Operative treatment may be required for an impending or existing fracture and intractable pain. The goals of surgeryare to provide local tumor control and allow immediate weight-bearing and function. Radiation therapy is oftenindicated postoperatively.

� Detailed preoperative evaluation is required to assess the local extent of bone destruction and soft-tissue in-volvement, involvement of other skeletal sites, and the overall medical and oncological status.

After the lungs and liver, the skeleton is the most common siteof metastatic disease1,2. Prostate, breast, lung, kidney, and thyroidcancers account for 80% of all skeletal metastases1-3. The femur,spine, humerus, pelvis, ribs, and skull are reported to be themost commonly affected sites, in that order4-6. The prolongedsurvival of more patients with cancer has led to increasing num-bers of individuals with metastatic bone disease. The exact inci-dence of bone metastasis is unknown, but it is estimated that350,000 people die with bone metastases annually in the UnitedStates alone7. Overall management of metastatic bone disease isestimated to result in as much as 17% of the total direct medicalcosts of cancer treatment in the United States8.

Metastatic bone disease is a major contributor to thedeterioration of the quality of life of patients with cancer. Im-pending and actual pathological fractures initiate the period ofdependent care for many of them. The majority of metastaticbone lesions are treated effectively with nonsurgical modalitiessuch as radiation therapy, chemotherapy, immunotherapy, hor-monal therapy, bone-seeking isotopes, and bisphosphonates9-12.

The use of chemotherapeutic and hormonal agents hasimproved the survival of patients with metastatic bone disease13,14.Randomized trials comparing the newer class of aromatase

inhibitors with a progestational agent for postmenopausalwomen with metastatic breast cancer have shown better survivalin the former group15,16. The combination of chemotherapywith a monoclonal antibody to HER-2 (trastuzumab)17 or thecombination of docetaxel and an oral 5-fluorouracil agent(capecitabine)18 has also been shown to improve the survivalof patients who have metastatic breast cancer when comparedwith that of patients treated with standard chemotherapyalone.

Bisphosphonates reduce bone resorption by inhibitingosteoclast function, although direct and poorly understoodantineoplastic effects may also occur. Administration of clod-ronate to patients who had breast cancer and were at high riskfor distant metastases was shown to reduce the incidence andnumber of new osseous and visceral metastases19. The additionof pamidronate to antineoplastic therapy for patients who hadstage-IV breast cancer and osteolytic metastases resulted in asubstantial reduction in the prevalence of skeletal complica-tions (51% [186 of 367 patients] compared with 64% [246 of384 patients not given pamidronate]) and a reduced rate ofskeletal morbidity (2.4 compared with 3.7 events per year)20.Zoledronic acid normalized levels of N-telopeptide of type-I

Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor amember of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercialentity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice,or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

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COPYRIGHT � 2009 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED

J Bone Joint Surg Am. 2009;91:1503-16 d doi:10.2106/JBJS.H.00175

collagen within three months in 179 (81%) of 220 patientswho had breast cancer with bone metastases, 135 (70%) of193 patients with hormone-refractory prostate cancer, andseventy (80%) of eighty-seven patients with non-small-celllung cancer21. A normalized level of N-telopeptide of type-Icollagen within three months after treatment, as comparedwith a persistently elevated level, was associated with reducedrisks of skeletal complications (pathological fracture, the needfor palliative radiation therapy or surgery to bone, and hy-percalcemia of malignancy) and death21. Zoledronic acid (4 mginfused over fifteen minutes) was also shown to reduce the rateof skeletal complications in patients with bone metastases fromsolid tumors other than breast and prostate cancer 22. However,bisphosphonates given intravenously at high doses or rapidlywere shown to be associated with osteonecrosis of the jaw aswell as with renal dysfunction23,24. More recently, anti-angiogenicagents were also shown to be effective in the management ofmetastatic bone disease: SU11248, a multitargeted receptortyrosine kinase inhibitor, demonstrated antitumor activity inmetastatic renal cell carcinoma25.

Treatment of pathological fractures with closed reductionand immobilization has been shown to be ineffective. Gainorand Buchert performed a study of 129 pathological fractures oflong bones in 123 patients who had been treated with a varietyof methods and followed until death or at least one year after thefracture26. They observed fracture-healing in 87% (twenty-six)of thirty patients who were treated with internal fixation andradiation therapy and lived more than six months comparedwith 57% (thirteen) of twenty-three patients who had a similarsurvival time but were treated with cast immobilization andradiation therapy26. As a result, those authors recommended theuse of internal fixation and postoperative radiation.

Patients who have a slow-growing tumor that is responsiveto chemotherapy and radiation therapy (such as multiple mye-loma) and who have a pathological fracture of a non-weight-bearing bone may be initially treated nonoperatively. Operativetreatment may be required for patients with an existing or im-pending pathological fracture or with intractable pain that doesnot respond to any nonoperative procedures27-29.

Operative intervention for metastatic bone disease isusually a palliative procedure. The goals of surgery are to achievelocal tumor control and structural stability of the surgicallytreated site and to restore function as quickly as possible.Ideally, operative treatment should allow immediate functionand weight-bearing with the least possible morbidity and re-habilitation. Operative reconstruction in patients who havebone metastases must also be reliable and durable in accor-dance with the expected duration of survival, which may beprolonged for patients with breast, prostate, or renal cancer30-33.Failure to achieve one of these goals usually necessitates asecond operative intervention, leading to additional impair-ment of an already compromised quality of life. In their 1958article, Bremner and Jelliffe stated that: ‘‘Most patients suf-fering long-bone pathological fracture have widespread dis-ease, but it is wrong and unkind to regard this misfortune as aterminal event warranting only the simplest of symptomatic

treatment. Recognition of this state of affairs demands thegreatest expedition in returning the patient to comfort andmobility, that he may better enjoy his remaining months.’’34

This statement is even more relevant today because of theimproved survival of patients who have metastatic bone dis-ease and the newer techniques available for tumor resectionand subsequent reconstruction of the defect.

The techniques for operative treatment of bone metas-tasis differ considerably from those used to fix a traumaticfracture because malignant tissue may need to be removed andbecause pathological fractures are associated with impairedbone-healing. The latter problem is attributed to extensivebone loss and destruction and to the postoperative radiationgiven to most patients27,28,35,36. These unique features of theoperative treatment of metastatic bone disease led to high ratesof failure when standard fixation techniques were used. Yazawaet al. reported that 8.8% (thirteen) of 147 patients with a totalof 166 metastatic lesions of the femur or humerus had a failureof operative treatment37. The reasons for failure included poorinitial fixation, improper implant selection, and progressionof disease within the operative field. Similarly, Wedin et al.reported a failure of operative treatment, requiring a reoper-ation, of 11% (twenty-six) of 228 metastatic lesions in 192patients36.

The present review summarizes the principles by whichpatients who require operative treatment of metastatic bonedisease are evaluated and managed. Adequate preoperativeevaluation and adherence to surgical strategy may decrease thehigh rate of complications and reoperations in patients withmetastatic bone disease.

IndicationsAlthough planned operative treatment for patients with meta-static bone disease should not be delayed, establishing the di-agnosis and preoperative evaluation and staging must not berushed. This process, which must be thorough, should allowdelineation of the osseous and soft-tissue extents of the lesionand their relationship to adjacent structures. It is also necessaryto determine the overall skeletal involvement of the tumor, todetect any other metastases that may require concomitantoperative treatment, and to evaluate the patient’s overallprognosis. Since the majority of patients who present withmultiple skeletal metastases have an established diagnosis ofcancer, clinical and radiographic evaluations are usually aimedat evaluating the extent of the disease and its complicationsrather than at identifying its site of origin3,38. However, a sys-temic and detailed workup is required for patients who presentwith metastatic bone disease without an established diagnosisof cancer. Patients with a history of cancer who have a solitarybone lesion should not be assumed to have metastatic disease,or treated as if they do, unless a histological diagnosis has beenobtained (Fig. 1).

The medical history should include the current onco-logical status and related treatments and medications. In casesof spinal metastases, the medical history should focus onsensory and motor dysfunctions, walking ability, and urinary

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and/or bowel incontinence. The physical examination shouldinclude an evaluation of the principal symptomatic area as wellas other symptomatic sites. It should focus on the extent of soft-tissue tumor extension and its relationship to the neurovascularbundle of the extremity, the neurovascular status of the affectedextremity, the presence of limb edema, muscle strength, and therange of motion of the adjacent joints. Assessment of thesphincter is mandatory for patients who have spinal metastases.

Laboratory studies should include complete hematologicand metabolic evaluations. Patients who have metastatic bonedisease are often treated with chemotherapy and may haveanemia and low platelet counts that must be addressed prior toan operation. Hypercalcemia most often develops in patientswith squamous-cell lung cancer, breast cancer, kidney cancer,and certain hematologic cancers (particularly multiple mye-loma and lymphoma). The signs and symptoms of hypercal-cemia are nonspecific, and the clinician should have a highindex of suspicion for this condition. Common symptoms in-clude fatigue, anorexia, and constipation. If untreated, a pro-gressive increase in the serum calcium level will likely result indeterioration of renal function and mental status. Death ulti-mately results from renal failure and cardiac arrhythmias.

Secretion of humoral and paracrine factors by tumorcells stimulates osteoclast activity and proliferation, and there

is a marked increase in the markers of bone turnover7,39. Nu-merous biochemical markers have been identified as corre-lating with bone turnover and resorption, although the valueof these markers for monitoring the response to therapy or forthe detection of bone metastases is still under investigation.Levels of bone-specific alkaline phosphatase, osteocalcin, andtype-I procollagen C-propeptide in serum are indicators ofosteoblast activity, whereas serum levels of C-terminal telopep-tide of type-I collagen and tartrate-resistant acid phosphataseand urinary levels of type-I-collagen cross-linked N-telopeptidesare markers of osteoclast activity40-42.

When the diagnosis of metastatic bone disease is stronglyconsidered, plain radiographs should be made of the affectedsite as well as of any other site at which the patient reports boneor joint pain. A computed tomography scan may also be re-quired to detect metastases located in the shoulder girdle,spine, and pelvis because of the complex anatomy of thesesites. Metastases located in long bones require biplanar radio-graphs because a single view may not provide enough in-formation with which to evaluate the full extent of boneinvolvement (Figs. 2-A and 2-B). The combined results ofthese imaging studies will define the extent of bone destructionand soft-tissue extension. The latter may be relevant when thetumor is located in close proximity to a major neurovascular

Fig. 1

Algorithm for evaluation of a patient with a known history of cancer and an aggressive

bone lesion.

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bundle. Metastases located in long bones require plain radio-graphs of the entire extent of the bone in order to exclude thepossibility of additional metastases for the purpose of surgicalplanning. Missed metastases proximal or distal to the level offixation could cause pathological fractures on weight-bearingon the operatively treated extremity. Computed tomographyscanning of the chest should also be routinely done as ascreening study to rule out lung metastases or, alternatively, todetermine whether the lung is the site of a heretofore unknownprimary lesion.

A total-body bone scintigraphic evaluation withtechnetium-99m methylene diphosphonate is recommendedprior to operative intervention. It allows detection of additionalmetastases that may require simultaneous surgical treatment.Bone scanning is highly sensitive for most bone lesions. Traceruptake, however, is not specific for metastatic bone disease andmay spuriously display a large variety of inflammatory, infec-tious, posttraumatic, and other benign conditions. Therefore, aplain radiograph should be made of any site that is found to be

positive on the bone scan. It should be borne in mind that bonescanning is not a substitute for plain radiographs of the entireaffected bone or other sites with bone pain because some tumors(such as renal cell carcinoma, multiple myeloma, metastaticmelanoma, and thyroid carcinoma) may not be evident on abone scan.

A sagittal, as well as axial and coronal, multilevel T1-weighted magnetic resonance imaging scan with gadoliniumenhancement is a useful screening tool for patients who havespinal metastasis. It allows evaluation of the extent of medul-lary and extraspinal disease and spinal cord and nerve rootcompression. This information is essential when one is decidingwhether to perform an operation or to treat the patient non-operatively and, if the decision is to operate, which levels requiredecompression and fixation.

Operative treatment of metastatic bone disease cannot becarried out without an established histological diagnosis. Whena patient has no previous histological diagnosis of metastaticbone disease, a biopsy is required to establish the diagnosis

Fig. 2-A Fig. 2-B

Anteroposterior (Fig. 2-A) and lateral (Fig. 2-B) radiographs showing metastatic breast carcinoma of the

distal part of the femoral diaphysis. While the anteroposterior radiograph gives the impression of relatively

intact cortices, the lateral radiograph shows clear cortical destruction with tumor extension into the surrounding

soft tissues.

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and exclude tumors that predictably respond to nonoperativetreatment (e.g., lymphoma) or that require a different treat-ment strategy (e.g., sarcoma). Core-needle biopsies have beenshown to have higher diagnostic accuracy than fine-needleaspirations for determining the type, grade, and specific diag-nosis of musculoskeletal tumors43. Examination of osseousmaterial obtained after reaming a bone lesion may not con-tribute to an accurate diagnosis, and the results of such anevaluation should be interpreted with caution and an under-standing of its limited value.

The indications for operative treatment of long-bone andpelvic girdle metastases include impending and pathologicalfractures and intractable pain27-29,44. Patients with certain typesof cancer who had a solitary bone metastasis were shown tohave better survival than patients with similar types of cancerand multiple bone metastases45-47. However, resection of suchlesions was not shown to improve the outcome48. Operativetreatment of spinal metastases is indicated for patients withspinal instability or spinal cord compression49-53. Patients witha very short life expectancy would not benefit from an opera-tion because of the rapid general deterioration of their func-tional and physiological status and because of their inability toexecute a minimal rehabilitation protocol. Considerations re-garding the expected survival, the overall medical status andquality of life, and the magnitude of the operation and reha-bilitation potential all contribute to the decision-making pro-cess54,55. It is difficult and impractical to set a rigid time frame,but six to twelve weeks of expected survival is generally theminimum required for relatively simple procedures such asintramedullary nailing, and a minimum of six months is nec-essary for more complex procedures such as acetabular or en-doprosthetic reconstruction.

The mere presence of lung metastases is not a contraindi-cation to operative intervention since certain groups of patientswith lung metastases have a relatively prolonged survival withreasonable respiratory function56. In a prospective study of 460patients in whom a fracture or an impending fracture of theacetabulum or a long bone had been treated operatively, asdocumented in the skeletal metastasis registry of the Scandina-vian Sarcoma Group, several clinical variables were recognized asbeing prognostically important in identifying patients who are athigh risk of dying in the first few months after an operation57.Pathological fracture, visceral metastases, a hemoglobin levelof <7 mmol/L, and lung cancer were independent negative

prognostic factors for one-year survival, whereas myeloma wasfound to be the only positive prognostic factor57. Similar resultswere reported by Nathan et al., who studied 191 patients whohad undergone surgery for metastatic bone disease; they foundthat the Eastern Cooperative Oncology Group performancestatus, number of bone metastases, presence of visceral me-tastases, and hemoglobin level were independent predictorsof survival58. It is, therefore, advisable to collaborate with theresponsible medical oncologist throughout the decision-makingprocess to evaluate the patient’s oncological status and lifeexpectancy and to coordinate the planned operation with anyother treatments planned for that patient.

Impending Pathological Fractures and Spinal InstabilityPathological fracture of a long weight-bearing bone has alwaysbeen a consistent and clear indication for operative intervention.Identifying an impending fracture (i.e., identifying a metastaticlesion of a bone that is at risk of fracture) and recommendingits prophylactic fixation in a patient with metastatic bonedisease is an important issue. Elective fixation prevents the in-tense pain and the loss of function associated with a pathologicalfracture, and it is easier to perform than fixation of an existingpathological fracture. In addition, Ward et al. documented thatpatients who had prophylactic fixation of an impending fracturehad a shorter hospital stay (mean, 5.6 compared with 7.8 days)and a higher likelihood of being discharged home rather thanto a nursing home or rehabilitation facility (77% compared with36%) as compared with patients who were treated surgicallyfor an existing pathological fracture59. It should be noted thatthat study was nonrandomized and retrospective, the patientsdid not undergo open curettage of the metastatic lesion, andpolymethylmethacrylate was not used for fixation.

A common conception is that lytic metastases are likely tocause a pathological fracture while the new bone that is laid downby blastic metastases actually may increase cortical strength andmake the bone locally harder28. Saad et al. retrospectively reviewedthe cases of 3049 patients with bone metastases and found thatthose with breast cancer, who usually have lytic bone metastases,had a higher rate of pathological fractures (35%; 393 of 1130)than did patients who had prostate cancer (19%; 122 of 640),in whom metastatic lesions are more often blastic60. Recentstudies indicate that the risk of skeletal complications in bothpatients with breast cancer and those with prostate cancer isstrongly related to the rate of bone resorption61,62.

TABLE I Mirels’s Scoring System for Risk of Pathological Fracture65

Score (points) Site Radiographic Appearance Bone Width Involved Pain

1 Upper extremity Blastic <1/3 Mild

2 Lower extremitynon-peritrochanteric)

Mixed (blastic-lytic) 1/3-2/3 Moderate

3 Peritrochanteric Lytic >2/3 Functional*

*Aggravated by function.

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Because of anatomical considerations, the definition of animpending fracture differs among the three major anatomicalsites (long bones, acetabulum, and vertebrae) at which opera-tive intervention for metastatic bone disease is often performed.

Numerous reports in the English-language literature de-scribe attempts to identify impending fractures in long bones.Harrington’s classic definition of an impending pathologicalfracture of a long bone includes cortical bone destruction of‡50%, a lesion of ‡2.5 cm in the proximal part of the femur, apathological avulsion fracture of the lesser trochanter, or per-sistence of stress pain despite radiation therapy 28.

An avulsion fracture of the lesser trochanter in the ab-sence of known antecedent trauma may be the initial manifes-tation of unrecognized metastatic bone disease. Phillips et al.hypothesized that these fractures occur when metastatic in-volvement of the intertrochanteric region becomes so markedthat the normal pull of the iliopsoas muscle results in avulsion63.Bertin et al. described four patients in which this occurred; thefractures healed, but a pathological subtrochanteric fracturesubsequently occurred in three of the patients64.

Mirels’s scoring system is based on four parameters (site,radiographic appearance, size, and related pain) for predictingthe risk of fracture and for recommending appropriate treatment(Tables I and II)65. Mirels’s system has the advantage of beingrelatively simple. It is based on clinical evaluation and plainradiographs and has been shown to be reproducible, valid, andmore sensitive than clinical judgment across experience levels66,67.It is important, however, to realize that some patients with animpending fracture may not experience pain. Fidler reportedthat nine of nineteen patients who underwent prophylacticfixation of an impending fracture had not experienced painbefore the impending fracture had been diagnosed68.

Because of the complex anatomy of the acetabulum and thevertebrae, a simple definition of impending or pathological fractureis neither possible nor useful for planning surgical reconstruction atthose sites. Instead, the location and extent of cortical destructionare used to evaluate the biomechanical impact on function.

Although the pelvis is a very common site of bone me-tastases, operative treatment of lesions in this area has notattracted as much attention as that in long bones or vertebrae.Operations are rarely required for pathological fractures of thepelvis other than those involving the acetabulum. In his 1981report on fifty-eight patients who had a pathological fractureor cortical destruction of the acetabulum because of metastaticdisease, Harrington classified the fractures on the basis of spe-cific biomechanical deficiencies in the periacetabular bone44.

Class I indicates that the lateral cortices and superior andmedial walls are structurally intact; Class II, that the medialwall is deficient; Class III, that the lateral cortices and superiorwall are deficient (Fig. 3); and Class IV, that there is extensiveacetabular involvement (of the lateral cortices and superior andmedial walls)44. Destruction of the superior and medial walls isusually considered to constitute mechanical compromise, thusnecessitating operative intervention29.

The debate about prophylactic fixation for the preventionof pathological fractures of long bones can also be applied tospinal metastases. Spinal instability is presumed if there is tran-sitional deformity, vertebral body collapse of >50%, tumor in-volvement of two of three columns, or involvement of the samecolumn at two or more adjacent levels69-71. Kostuik et al. at-tempted to define spinal stability using a two-column concept ofspinal architecture72. According to their concept, the anteriorcolumn consists of the entire vertebral body whereas the pos-terior column consists of the pedicles, laminae, and spinousprocess. The anterior column is further divided into anteriorand posterior halves as well as right and left sides, which resultsin four quadrants of the vertebral body. The posterior column isdivided into right and left sides, for a total of six vertebralsegments. Kostuik et al. considered the spine to be stable when

TABLE II Mirels’s Scoring-Based Treatment Recommendations65

Total MirelsScore (points) Risk of Fracture

RecommendedTreatment

‡9 Impending Prophylactic fixation

8 Borderline Consideration of fixation

£7 Not impending Nonoperative treatment

Fig. 3

A plain radiograph showing a Class-III acetabular

metastasis, according to the Harrington classifica-

tion, which includes deficiency of the lateral cortices

and the superior wall44. A computed tomography

scan is required to determine the exact extent of bone

and cortical destruction.

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no more than two segments were destroyed, and they con-sidered it to be unstable when three or more segments weredestroyed. More recently, Tomita et al. grouped spinal tumorsinto three anatomical categories: intracompartmental (con-finement of the tumor to the osseous elements of the vertebra),extracompartmental (occurrence of cortical breakthrough andtumor extension into the surrounding tissues), and metastasesat multiple levels51. These parameters as well as the grade of thelesion, the presence of visceral metastases, and the extent ofmetastatic bone disease elsewhere in the skeleton allowed thedetermination of a prognostic score, a general treatment plan,and a specific surgical strategy 51.

Spinal cord compression is a devastating complication ofmetastatic bone disease; it is defined as a mass lesion caused bytumor extension into the epidural space or a pathological spinefracture with displacement of the cord. It may present as asurgical emergency, with a rapidly evolving neurological deficit,or more subtly, with slowly progressive neurological dysfunc-tion and pain49,73. The expected recovery of patients withneurological dysfunction is related to the acuity of the symp-tom onset. Patchell et al. performed a randomized, nonblindedmulti-institutional study to evaluate the efficacy of operativetreatment and radiation therapy compared with that of radi-ation therapy alone in patients with spinal metastasis andspinal cord compression74. The patients included in their studyhad an epidural mass compressing the cord with at least oneneurological sign or symptom (including pain), good perfor-mance status, and a life expectancy of three months or more74.The primary end point in that study was the ability to walk,and secondary end points were urinary continence, musclestrength, functional status, the need for steroid and/or anal-gesic medications, and survival. After an interim analysis, the

study was ended because the criterion of a predetermined earlystopping rule was met: significantly more patients were able towalk after treatment in the surgery group (forty-two of fifty;84%) than in the radiation-therapy group (twenty-nine offifty-one; 57%) (odds ratio 6.2 [95% confidence interval, 2.0 to19.8]; p = 0.001). When the analysis included only the thirty-two patients who had been unable to walk when they enteredthe study, it was found that significantly more patients in thesurgery group than in the radiation group regained the abilityto walk (ten of sixteen compared with three of sixteen; p =0.01). Operative treatment also resulted in substantial differ-ences in continence (156 compared with seventeen days),survival time (126 compared with 100 days), muscle strength,functional ability, and reduction in steroid and opioid use. Theauthors concluded that direct decompressive surgery andpostoperative radiation therapy is superior to treatment withradiation therapy alone for patients who have spinal metastasesand spinal cord compression.

Intractable Pain and Solitary MetastasesOperative intervention may be required for relief of intractablepain associated with bone metastasis that has caused extensivebone destruction and has responded poorly to chemotherapy,narcotics, and radiation therapy 27,29,75.

A controversial issue is the operative management of asolitary bone metastasis and whether its removal has an impacton the patient’s survival. Operative treatment may be consid-ered for tumors that are slow-growing, that are associated with a

Fig. 4

Illustration showing reconstruction of a tumor cavity with a

cemented intramedullary nail.

Fig. 5

Plain radiograph showing the reconstructed tumor

cavity.

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good two-year survival rate, and for which there is no de-pendable oncological treatment. Metastatic renal cell and thy-roid carcinomas are probably the only solitary bone metastasesfor which resection has been shown to be beneficial in terms ofpatient survival29,56,76-80.

Operative TechniqueThe aims of operative management of bone metastases, regard-less of the anatomical site, are relief of pain and restoration offunction by achieving local tumor control and immediate me-chanical stability. Local tumor control is usually accomplished bypostoperative radiation therapy, with or without prior operativeremoval of the tumor. Tumor removal requires adequate expo-sure and should include curettage, drilling with a high-speedburr, and occasionally resection of the affected bone segment.Tumor removal may be associated with increased blood loss, anincreased risk of infection, and local tumor seeding. These risksshould be considered when local tumor progression cannot becontrolled by nonoperative means and operative treatment isplanned. For example, it may not be necessary to remove meta-static tumors, such as multiple myeloma and breast cancer, thatare responsive to radiation therapy. Structural stability is ach-ieved by using orthopaedic implants, with or without cement,and usually not with allografts or allograft-prosthesis com-posites, which rely on bone-healing27-29,35,81-83. Bone cement

augments structural stability and enables the patient to with-stand the stress of immediate motion and function.

Goetz et al. reported on a series of forty-three patientswith painful osteolytic bone metastases that had not respondedto previous chemotherapy or radiation therapy and weretreated with image-guided, percutaneous radiofrequency ablationof the tumor site84. Twenty-four (56%) of the forty-three lesionswere located in the pelvic girdle. Following radiofrequency ab-lation, 95% (forty-one) of the forty-three patients reported aclinically relevant decrease in pain. Although it has the advantageof being a minimally invasive treatment option for patients withintractable pain, radiofrequency ablation does not provide me-chanical reinforcement of the tumor cavity, and operativetreatment should be considered when such stability is required.

Selective arterial embolization within twenty-four hoursbefore the operation is recommended for patients who have ametastatic renal cell or thyroid carcinoma since surgical ma-nipulation of these hypervascular tumors may cause extensivebleeding29,85,86.

Long BonesOperative treatment of long-bone metastases usually consists ofclosed nailing, but wide exposure, tumor removal, and fixationwith cemented hardware may be required. Closed nailing is donein the case of an impending or actual pathological fracture withminimal bone destruction and fragment displacement4,59,81,87.

Fig. 6-A

Anteroposterior plain radiograph showing metastatic

renal cell carcinoma of the entire proximal part of

the humerus with extensive bone destruction and

pathological fractures along the proximal part of

the diaphysis and the surgical neck.

Fig. 6-B

Intraoperative photograph showing a modular tumor

endoprosthesisusedto reconstruct thedefectcreated

by resection of the proximal part of the humerus.

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Open exposure may be required in cases of pathological fracturewith considerable bone destruction27-29,77,82. The following ap-proach, which is our preference, entails adequate exposure of thetumor site with use of a large cortical window and tumor removalwith handheld curets and drilling with a high-speed burr. Re-construction begins with the introduction of an intramedullarynail. After the proper positioning and length are verified, the nailis partially withdrawn and the entire tumor cavity is filled withpolymethylmethacrylate. The nail is then pushed back into themedullary canal and fixed with interlocking screws (Figs. 4 and5). Intramedullary fixation devices are preferable for pathologicalfractures because of their superior ability to withstand mechanicalloads, because they support the entire length of the affected bone,and because normal bone-healing cannot be expected88,89. Forexample, a traumatic intertrochanteric fracture would be treatedappropriately with a compression hip screw and side-plate device,whereas a pathological fracture in the same anatomical site wouldbe best treated with a cephalomedullary nail. The use of side-plates for fixation is appropriate for lesions located in the upperextremity (for example, the humeral diaphysis), which is notsubjected to considerable weight-bearing, or in places where it isdifficult to use an intramedullary device (for example, the prox-imal tibial metaphysis).

Cases of extreme cortical destruction in which the re-maining cortices cannot support a fixation device, and par-ticularly in which the adjacent joint is destroyed, should betreated with resection and reconstruction with a cementedtumor prosthesis (Figs. 6-A, 6-B, and 6-C).

Amputations are rarely required but should be consideredfor palliation in cases in which bone destruction and tumor ex-tension into the surrounding soft tissues are too extensive toallow reconstruction following wide tumor resection and in casesof neurovascular compromise of the affected extremity 90-92.

Acetabulum and SpineIn accordance with the classification system that he developed,Harrington also developed specialized operative techniques toensure adequate support and fixation of the acetabular com-ponent of a total hip prosthesis in its normal anatomical po-sition and to allow transmission of weight-bearing forces intobone that is functionally capable of withstanding the load44.According to Harrington, patients with a Class-I lesion havesufficient periacetabular bone for conventional fixation of thecemented acetabular component. More recently, trabecular metalacetabular components have been used for that purpose inpatients treated preoperatively with therapeutic pelvic radia-tion93. Because of loss of medial structural continuity, Class-IIlesions require the use of a protrusio acetabuli cup. Class-IIIlesions, in which all three elements of the acetabular cavity areviolated, require a complex reconstruction of the missing cavitywith cemented Steinmann pins or cannulated screws as rein-forcement bars to support the protrusion cage. Class-IV le-sions require internal hemipelvectomy for tumor removal,which leaves major bone loss and pelvic discontinuity. So-called saddle prostheses have been used effectively for recon-struction in these Class-IV cases94. These prostheses, whicharticulate with the posterior part of the ilium, were originallydesigned for reconstruction in patients with a large acetabularbone deficiency, with or without infection, following total hiparthroplasty. Harrington et al. performed total hip arthroplastyin all of their patients35, and a similar surgical strategy wasreported by others75,85,95,96. It is possible, however, that somepatients with a Class-I lesion who have sufficient bone stockover the acetabular roof do not require joint replacement andcan be treated with intralesional curettage and internal fixationwith cement (Figs. 7-A and 7-B).

Like bone metastases elsewhere, spinal metastases oftenrespond favorably to nonoperative treatment modalities. Op-erative treatment of spinal metastases is usually indicated whena patient has spinal instability, a progressive neurological def-icit, intractable pain that is unresponsive to nonoperativetreatment, or a lesion that is not responsive to radiationtherapy 50,97,98. Harrington devised a five-category classificationscheme for the management of spinal metastases based on theextent of bone destruction and neurological compromise50.He recommended nonoperative treatment for patients whohad (1) no important neurological compromise, (2) bone in-volvement without collapse or instability, or (3) major sensoryor motor neurological compromise without substantial boneinvolvement. Operative treatment was recommended for pa-tients who had either (1) vertebral collapse with pain resultingfrom a mechanical cause, but with no important neurologicalcompromise, or (2) vertebral collapse or instability combinedwith major neurological compromise50. Recently, treatment

Fig. 6-C

Anteroposterior plain radiograph showing the

cemented proximal humeral endoprosthesis.

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options have been tailored according to the status of the tumorand the overall oncological stage. Tomita et al. developed ascoring system on the basis of a retrospective survival analysisof sixty-seven patients51. This system includes three majorparameters: (1) grade of malignancy, (2) presence and possi-bility of treatment of visceral metastases, and (3) presence andextent of bone metastases. A numerical value is assigned to eachcategory to calculate a prognostic score of 2 to 10 points. Aprognostic score of 2 or 3 points suggests survival for more thantwo years and a recommendation for aggressive treatment (i.e.,wide excision and fixation), and a score of 8, 9, or 10 points isindicative of short-term survival and a recommendation fornonoperative and supportive care. Palliative decompressive

surgery can also be considered for the latter group. This scoringsystem was shown to be reliable, with a strong correlation withsurvival, in a prospective study of sixty-one patients51.

Tokuhashi et al. used a system that included six cate-gories: general condition, number of extraspinal bone metas-tases, number of vertebral body metastases, metastasis tomajor internal organs, primary site of malignancy, and neu-rological compromise99. A numerical value was assigned toeach category, and a strong correlation was shown betweenpredicted and actual survival99. Enkaoua et al. retrospectivelyevaluated this scoring system in a study of seventy-one patientswho had spinal metastasis and confirmed its reliability as aprognostic tool100. They recommended, however, that patientswho have metastasis of unknown origin should receive a lowerscore. Tokuhashi et al. subsequently revised their originalsystem and reported that the correlation between the scoresderived with that system and the actual patient survival wasbetter than that with the previous version101. Ulmar et al.compared the validity of the scoring systems of Tokuhashi et al.and Tomita et al. with regard to their ability to predict theprognosis of patients who have spinal metastases of renal cellcarcinoma and found the former to be superior102.

Historically, laminectomy has been the surgical optionfor treatment of spinal cord compression, but laminectomy byitself does not address the anterior pathological involvementand thus may not suffice for cord decompression. Moreover,removal of the posterior elements may worsen the existinginstability and deformity caused by tumor-related destructionof the vertebral body. Indeed, studies performed in the early

Fig. 7-A

Coronal view of a computed tomography scan showing a Harrington

Class-I44 acetabular metastasis from renal cell carcinoma.

Fig. 7-B

Plain radiograph showing reconstruction of the acetabular cavity with cemented Steinmann pins.

The articular cartilage remained intact.

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1980s showed that a combination of surgery and radiation wasno better than radiation alone103,104. Operative treatment was,therefore, abandoned for more than two decades, duringwhich spinal cord compression was usually treated with high-dose corticosteroids and radiation therapy, yielding an ap-proximately 50% overall rate of ambulatory function105-107.

Improvements in operative techniques and implantshave enabled the development of comprehensive decompres-sion and fixation. Weigel et al. analyzed the surgical outcomesand quality of life of patients who had undergone operativetreatment consisting primarily of anterior decompression andstabilization52. They reported neurological improvement intwenty-six (58%) of forty-five patients, and fourteen (70%)of twenty patients who had been unable to walk before theoperation were able to walk postoperatively. Pain relief wasreported by sixty-eight (89%) of seventy-six patients.Other retrospective studies on direct tumor removal with ef-ficient cord decompression and spinal fixation have shownneurological recovery in 70% to 90% of patients and im-provement in pain control and the quality of life in 80% to90%49,74,108,109.

Operative treatment of spinal metastases should includeremoval of the tumor, and fixation should restore as much ofthe normal architecture, alignment, and stability as possible.Vertebrectomy has been shown to achieve mechanical stabilityand good clinical outcomes110-112. It may be accomplishedthrough either an anterior approach (with use of a thoracot-omy for the thoracic vertebrae or a retroperitoneal approachfor the lumbar vertebrae) or a posterolateral approach113.Fixation with cages and anterior plates is the preferred tech-nique in most instances. Circumferential fixation is advisablewhen posterior elements are also involved.

The precise role of kyphoplasty and vertebroplasty in thetreatment of spinal metastases is still undetermined. Verte-broplasty involves direct injection of polymethylmethacrylateinto the affected vertebral body to support its frame and in-duce immediate stability. Kyphoplasty involves the use of aninflatable balloon to restore the vertebral body height andcorrect the kyphotic deformity followed by the injection ofpolymethylmethacrylate. Both procedures may be done withthe use of local anesthesia, and both require fluoroscopicguidance. These procedures are indicated for patients whohave spinal metastasis and either are in poor medical conditionor have a short life expectancy, have intractable pain, or havespinal instability without a neurological deficit. The benefits ofinjection of polymethylmethacrylate into a fractured vertebralbody with a metastatic tumor include stabilization, correctionof about 45% of the kyphotic deformity and vertebral com-pression, and most importantly excellent and immediate paincontrol in about 85% of treated patients105-109. Many patientscan walk immediately after the procedure. Although rare,potential complications of the procedures include asymp-tomatic leakage of cement into the spinal canal (occurring inapproximately 10% of patients), particularly in the presence ofa defect of the posterior wall of the vertebral body, and epi-dural spinal cord compression114-118.

Postoperative CareIf mechanical stability has been achieved, full weight-bearingon the affected extremity and passive and active range-of-motion exercises of the adjacent joints should be performedas soon as possible as determined on the basis of the wound-healing and the patient’s ability. Early discharge from thehospital will generally enhance the patient’s morale and min-imize the interruption of an ongoing oncological program oftreatment.

Following wound-healing, patients are referred for ad-juvant radiation therapy to decrease the likelihood of localtumor recurrence. This usually consists of 3000 to 3500 Gy ofexternal beam radiation given in several fractions, usually be-ginning no earlier than two weeks after the operation119. In onestudy, patients with metastatic bone disease who underwent anoperation and were given postoperative radiation therapy hadhigher rates of normal functional status and required fewersubsequent orthopaedic procedures than those treated with anoperation alone120. However, the better survival in that groupmight have been due to a referral bias consisting of patientswith a better prognosis and medical status being assigned tothat group. Adjuvant chemotherapy and immunotherapy aregiven on the basis of the specific tumor type and the relevanttreatment protocol.

Functional and Oncological OutcomesThe survival of patients with cancer is usually determined moreby the metastatic load in other sites than it is by metastases in theskeleton. Local tumor control, pain relief, and function are,therefore, the most appropriate criteria for evaluating the efficacyof operations done for metastatic bone disease. Although oper-ative treatment is often carried out for metastatic bone disease,there have been only a few reports on the functional and onco-logical outcomes, which have demonstrated the ability to walk orgood-to-excellent function in >50% of the patients who haveundergone surgery 27,29,44,49,50,74,75,82,85,121. Major resection of meta-static lesions with prosthetic reconstruction has been shown tobe associated with tolerable morbidity and to be rewarding interms of functional results and local tumor control27,122-126.

The above studies vary considerably with regard to theoutcome parameters used to evaluate success. Instrumentsused for this assessment have included the MusculoskeletalTumor Society and the Toronto Extremity Salvage Score scales,which were designed to evaluate function following limb-sparing tumor resection. Also used were the Eastern Cooper-ative Oncology Group scale, designed to evaluate progressionof disease and its impact on daily living abilities, as well as theShort Form-36 questionnaire for evaluating general healthstatus54,127-129. The most consistent result of operative inter-vention for metastatic bone disease is the alleviation of pain,which was described by Bremner and Jelliffe in 1958 to be themost striking benefit of operative treatment34. Similar obser-vations of postoperative pain relief have been consistentlymade by others27,59,75,85,130-136. A reoperation because of eitherlocal tumor progression or failure of fixation has been reportedin less than 10% of patients27,29,36,49,76. n

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Jacob Bickels, MDShlomo Dadia, MDZvi Lidar, MDNational Unit of Orthopedic Oncology (J.B. and S.D.) and

Spine Care Unit (Z.L.),Tel-Aviv Sourasky Medical Center,6 Weizmann Street, Tel-Aviv 64239, Israel.E-mail address for J. Bickels: [email protected]

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