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Metastatic Bone Disease

Faculty and Disclosures

CME/CE Information

Introduction
Effective treatments for prevention of bone metastases have begun to replace old methods
of treatment after the fact. At the same time, new surgical procedures and devices can
restore function more quickly and more durably than before. Aggressive surgical
resection of metastatic bone lesions in selected patients now offers the hope of long-term
survival and even of potential cure where once there was no hope of survival. This
symposium provided an update on the knowledge required for rendering optimum care to
patients with metastatic bone disease.

Epidemiology: Avoiding the Pitfalls

Mary O'Connor, MD,[1] spoke on the diagnosis of metastatic disease. Cancer represents
the second most common cause of death in the United States, where there are 1.2 million
new cases of invasive cancer per year. In men, the most common sites are prostate, lung
and colon; in women, they are breast, lung, and colon. Survival continues to improve but
only slightly, with the average 5-year survival rates for US whites in lung, breast, prostate
and colon cancer of 15%, 87%, 95%, and 64%, respectively. Distressingly, African
Americans on average have 10% to 15% lower survival rates in the same interval. Longterm survival in some groups means that the orthopaedic surgeon must plan for durable
fixation of pathologic fractures in many cases.
Orthopaedic tumor specialists often see patients for whom there has been a mistake in
diagnostic or surgical management that has adversely affected function or survival. These
errors often share a common feature: a rush to judgment and treatment rather than an
informed, methodical evaluation. One possible cause for the rush is the extreme anxiety
the discovery of metastatic disease provokes in the patient and family. Many people
equate "cancer in the bones" with certain death, so the emotional reactions may be
extreme. Not surprisingly, the physician feels pressured to act quickly. This scenario sets
the stage for some of the more common pitfalls orthopaedic surgeons must avoid in the
management of metastatic bone lesions.

While it is important to be compassionate and supportive, physicians must also allow

themselves distance and time so that emotion does not overwhelm good judgement. A
few days' delay will not have any significant impact on outcome, but will allow time for
the physician to process all the information and obtain the consultations necessary to
optimize the patient's care. It may be best to admit the patient to the hospital with the
diagnosis of pathological fracture for bed rest and evaluation, obtain a medical and/or
medical oncology consultation, and "sit on the patient aggressively" for a few days. It is
important to order effective thromboembolism prophylaxis, because these patients have a
significant risk of deep venous thrombosis and pulmonary embolism.

Evaluation Strategy
Dr. Albert Aboulafia,[1] who spoke on evaluation, recommended following a 4-step
systematic evaluation of every patient with a suspected metastasis: history and physical,
laboratory exams, plain radiographs and imaging studies, and followed finally by biopsy.
In bone metastasis, the history is the single most powerful diagnostic tool, but is
underutilized by orthopaedic surgeons. Any history of cancer, no matter how remote,
should be completely considered. Often, patients may believe they have been cured, and
will not mention their cancer unless asked more than once. Questions should include
those on:

risk behaviors and exposures (eg smoking, alcohol abuse)

neglected screening examinations

new symptoms, such as cough, blood in the urine, a lump on the neck

The family history may reveal a significant cancer risk, particularly in first-generation
female relatives with breast cancer.
Although orthopaedic surgeons may not wish to become involved in the discovery of the
primary tumor in a patient with a suspected metastasis, a few simple screening
procedures can be easily performed and have a high probability of yielding the correct
diagnosis. The following screening examinations or studies are directed at the most likely
origins of bone metastases:

examination of the thyroid by palpation

plain PA and lateral x-ray of the chest

mammogram

urinalysis

digital rectal examination in males

The physical examination should cover the area of interest as well as the skin, the local
and regional lymph nodes, and the screening exams mentioned above. Labs may include:

a complete blood cell count

Chem-25, SPEP/UPEP

Prostate-specific antigen in men

urinalysis

Predicting the Risk of Pathological Fracture

Dr. Gary Friedlaender[1] described the history of guidelines for assessing pathologic
fracture risk. The first studies, conducted by Beals and Snell between 1956 and 1961,
looked at pathologic fractures of the femur in patients with breast carcinoma metastatic to
bone. Of the 19 fractures that occurred in their first series, they found that 58% were
predictable using the following criteria:

presence of a metastatic lesion 2.5 cm in size or larger involving the femoral

cortex

presence of a defect of the same size in any location that caused pain to the patient

In 1973, Fidler[2] retrospectively studied 19 patients with pathological fractures of the

femur. He found that all patients with greater than 50% cortical involvement developed a
fracture. Based on this data, he recommended that patients with involvement of over half
of the cortex should undergo surgery to stabilize the bone. Zickel and Mourandian
studied 34 patients with lesions in the proximal femur and concluded that involvement of
even small parts of the cortex in the subtrochanteric region places the femur at high risk
for fracture and warrants prophylactic fixation.[3] Size of the lesion did not correlate with
risk of fracture.
In 1982, Harrington[4] recommended intramedullary nail fixation when greater than 70%
destruction of the cortex is present, rather than 50% cortical involvement. Harrington also
pointed out that many of the bone metastases that eventually lead to pathologic fracture

cause radiographic changes that are diffuse or difficult to measure, making risk
assessment difficult.
Several authors have demonstrated the limitations of using size-based criteria alone. In
1986, Keene and colleagues[5] reported that many metastases could not be accurately
measured from plain radiograph because they lacked a clear border between the lesion
and normal bone. Unable to identify a consistent relationship between the size of the
lesion and risk of fracture, the authors recommended using other criteria. In addition, in
metastatic cancer producing blastic lesions, the extent of bone destruction can be difficult
to assess from plain films. Size-based criteria may not be applicable to bony lesions
where the cortex cannot be effectively measured, such as those of the spine, ribs and
pelvis.
In 1989, Mirels[6] developed a scoring system to quantify the risk of pathologic fracture
based on a retrospective study of 78 irradiated metastatic bone lesions. Unlike the
previous studies, Mirels combined 4 different features of bone lesions in an attempt to
create a more reliable risk assessment. The system assigned points to the following 4
variables:

the location of the lesion (upper limb, lower limb, peritrochanter)

the degree of pain caused by the lesion (mild, moderate, severe)

the type of lesion (lytic, blastic, mixed)

the degree of cortex taken up by the lesion (<1/3, 1/3-2/3, >1/3)

Mirels' data indicated that on a scale of 12, a score of less than or equal to 7 is indicative
of a low-risk lesion. A score of 8 is associated with a 15% risk for fracture, while the risk
of fracture is 33% in patients with a score of 9. Mirels concluded that a score of 9 or
greater should be used to indicate the need for prophylactic fixation.

Table 1. Mirels' Scoring System

Variable

Site

Score
1

Upper limb

Lower limb

Peritrochanter

Pain

Mild

Moderate

Severe

Lesion

Blastic

Mixed

Lytic

Size

<1/3

1/3-2/3

>2/3

Upper Extremity Metastasis

Dr. Michael Rock[1] spoke on metastases to the upper extremities, where only 20% of
bony metastasis occur. Half of these metastases are in the humerus. However, the impact
on patient is as disabling as in the lower extremity.
In the proximal humerus, a hemiprosthesis with long stem or plates with
methylmethacrylate are normally used. In selected patients where prolonged survival is
anticipated, a custom prosthesis or an alloprosthetic composite is used. When using a
massive proximal humeral prosthesis, a Dacron vascular graft can be opened
longitudinally and fashioned to form a sling around the prosthesis, reducing the
likelihood of migration and dislocation of the humeral component.
In the humeral shaft, locked or cemented intramedullary rods are recommended. Flexible
intramedullary devices, even when cemented, have a tendency to migrate and are no
longer recommended. For these procedures, patients should be positioned carefully so
that an approach to the entire humerus is possible. If the humerus fractures or the locking
screws do not achieve adequate fixation, augmentation is necessary. Biopsy may be
obtained through the nail starting hole to confirm the diagnosis if needed.
Alternatively, a resection and shortening of the humerus may be chosen if the lesion is
less than 3 or 4 cm in length. A side plate with screws and methylmethacrylate is used for
fixation. A study from the Netherlands comparing nails to plates showed essentially equal
results.[7] Distal lesions in the diaphysis that cannot be rodded are treated with plates,
screws, and PMMA. In the distal metaphyseal humerus, dual reconstruction plates with
methylmethacrylate are used. Avoid an olecranon osteotomy if possible, as nonunion
rates are high when patients are radiated. In extensive lesions, a total elbow arthroplasty
is utilized.

Periacetabular Metastasis

Dr. Franklin Sim[1] discussed metastases to the pelvis, a frequent site of involvement in
which lesions cause considerable disability. Selection of the best treatment requires
careful consideration because of the extensive nature of the surgery and the much longer
recovery period. The goal is immediate stability for weight-bearing and durable fixation
that will avoid the need for another surgery. Routine radiographs are not sufficient to
evaluate bone loss, making CT scans recommended in virtually every case.
Dr. Sim presented the Harrington classification of periacetabular metastases, along with
recommended treatments (Harrington 1981)[8]:
Class I: Lateral cortices, superior, medial walls intact. These tend to be small cavitary
lesions. Standard total hip arthroplasty is sufficient to manage these smaller lesions.
Class II: Medial wall deficient or medial wall and dome. There is a high risk of medial
migration, making total hip arthroplasty with reinforcement of the medial wall with wire
mesh, a protrusio ring, and methylmethacrylate indicated. A variety of protrusio rings are
available, and selecting the best device will facilitate the procedure. The ring is molded to
fit the bone as much as possible. The femoral component must be selected so that there is
no impingement against the rim of the protrusio ring, which is more extensive than that of
a normal acetabular prosthesis.
Class III: Lateral cortices and dome are deficient. The optimal procedure involves the
use of multiple large threaded Steinmann pins drilled into remaining ileum,
methylmethacrylate, and a protrusio ring. Two groups of pins are inserted. One is inserted
distal to proximal into the posterior wall area, and the other is inserted through the ileum
from the anterior parts to support the anteriorly directed forces.
Class IV: Resection is required for potential cure. Wide surgical resection and allograft
or saddle prosthesis reconstruction are required, depending on the extent of the disease.
Major resections of metastatic lesion in the pelvis should be offered to those patients with
the best potential long-term survival. This group of patients is comprised virtually
exclusively of patients with solitary metastasis from thyroid and renal cell carcinomas,
and who have a very long (12 months or perhaps >24 months) disease-free interval
between the diagnosis of the primary tumor and the discovery of the metastasis.
Lesions and pathological fractures away from the articular surfaces are managed with
radiation and gradual return to function.

Metastasis in the Proximal Femur

Dr. Steven Gitelis[1] discussed metastases of the proximal femur, the object of the largest
proportion of operative procedures done for metastasis. Implant failure is a problem
secondary to prolonged survival and tumor progression. In the proximal femur, 44% of
fixation devices failed at 5 years.[9] Many of these failures were due to the use of a nail

plate device. Augmentation with methylmethacrylate adds considerably to the chances of

success when a nail plate is used.
Managing these lesions prophylactically is far superior to intervention after the fact. The
surgeon should carefully assess the risk of pathological fracture (see above) and intervene
proactively whenever possible. The entire femur should be examined to detect lesions
that may exist distal to the known lesion.
Some lesions should be resected rather than rodded. Patients who respond well to
chemotherapy, patients with renal tumors, diffuse disease present over several
centimeters of the femur should be considered for resection and reconstruction with a
modular oncology prosthesis.
Dr. Gitelis[1] presented the following recommendations for surgery, depending on the
involvement of the metastases:
Femoral neck or intertrochanteric region, remaining bone structurally adequate:

Side plate and methylmethacrylate or hemiarthroplasty

Femoral neck or intertrochanteric region, remaining bone structurally inadequate:

hemiarthroplasty fixed with cement

S ubtrochanteric region, remaining bone structurally adequate:

reconstruction nail and methylmathacrylate

Calcar replacement prosthesis

proximal femoral resection/ modular prosthesis

When replacing the entire proximal femur to below the level of the lesser trochanter,
bipolar implants are preferred over total hip implants even if there is some acetabular
osteoarthritis, due to the high rate of dislocation in these cases. A careful abductor repair
or a constrained cup may also reduce the chance of dislocation.
Subtrochanteric region, remaining bone structurally inadequate:

proximal femoral resection

replacement with modular prosthesis

Femoral and Tibial Shaft Metastasis

Dr. Ross Wilkins[1] noted that all patients with metastatic cancer should be treated with
bisphosphonates. In lesions of the distal femur and tibia, stable internal fixation with
adequate durability are the goals. Dr. Wilkins said he adds bone graft products from his
own commercial bone bank in many of these lesions.

Implications for Clinical Practice

To establish the risk of pathological fracture, the size of the lesion and other
factors should be considered. The Mirels scoring system is a useful tool because it
integrates several important risk parameters and is easy to remember and use.

Prophylactic fixation of impending fractures leads to superior outcomes when

compared with treatment after fracture, so the orthopaedic surgeon should have a
lower threshold for surgery in metastatic disease.

Selected patients may be managed with resection either to reduce the chance of
fixation failure or to increase the likelihood of long-term survival.

Bisphosphonates should be given to all patients with bone metastases.

More durable procedures, such as cemented hemiarthroplasty, are now

recommended for lesions of the humerus and femur.

Because of the risk of fat embolization, caution should be exercised when using
cement to fill the medullary cavity when rodding long bone lesions.

References
1. O'Connor MI. Symposium: Metastatic bone disease. In: Program and abstracts of
the 67th annual meeting of the American Academy of Orthopaedic Surgeons;
March 15-19, 2000; Orlando, Fla. March 17, 2000.
2. Fidler M. Prophylactic internal fixation of secondary neoplastic deposits in long
bones. Br Med J. 1973;1:341-343.
3. Zickel RE, Mouradian WH. Intramedullary fixation of pathological fractures and
lesions of the subtrochanteric region of the femur. J Bone Joint Surg Am.
1976;58:1061-1066.

4. Harrington KD. New trends in the management of lower extremity metastases.

Clin Orthop 1982;169:53-61.
5. Keene JS, Sellinger DS, McBeath AA, Engber WD. Metastatic breast cancer in
the femur: a search for the lesion at risk of fracture. Clin Orthop. 1986;203:282288.
6. Mirels H. Metastatic disease in long bones. Clin Orthop Rel Res. 1989;249:256264.
7. Dijkstra S, Wiggers T, van Geel BN, Boxma H. 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;160:535542.
8. Harrington KD. The management of acetabular insufficiency secondary to
metastatic malignant disease. J Bone Joint Surg. 1981;63A:653-664.
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femoral fractures. Clin Orthop. 1990;251:213-219.