Introduction
Virtually every cancer has the potential to metastasize. Following metastases
to nodes, lung, and liver, the skeleton is the fourth most common site for metastases.
Over the past several decades, an increase in the survival of patients with
bone metastases has been achieved through earlier detection using improved diagnostic
modalities and radiographic imaging techniques and through treatment advances
in chemotherapy regimens and radiation therapy combined with better surgical
approaches.
Skeletal Metastases
Skeletal metastases represent the major orthopedic complication of failed cancer
treatment and are commonly associated with disabling pain and pathological fracture.
Treatment of all patients with metastatic disease involves a multidisciplinary
team approach to include an oncologist, Radiotherapist, and orthopedic surgeon.
Advances in surgical techniques and internal fixation modalities have resulted
in great improvement in pain control and management of patients with skeletal
metastases. The main goals of treatment are to relieve pain, to improve function,
and to return patients, as soon as possible, to their previous environment.
The vast majority of skeletal cancers are of metastatic origin rather than primary
bone tumors. In most cases metastatic lesions are multifocal and show variable
radiographic features, while primary bone tumors demonstrate a typical presentation
by their anatomic site and radiographic features. The surgical approach for
primary bone tumor is curative by wide surgical resection, while for metastatic
disease surgical approach is palliative to restore function and to relieve pain.
In most instances of skeletal metastatic disease, the best treatment may not
appreciably extend the life span of the patient.
Within the skeleton the site of a metastatic lesion can be correlated with the
activity of the bone marrow The axial skeleton contains active hematopoietic
marrow, while the peripheral skeleton contains relatively avascular fatty marrow.
The axial skeleton, especially the thoracolumbar spine, represents the most
common site for metastases. Because of the relatively avascular marrow, metastases
below the elbow and knee are relatively rare. Many of these lesions are asymptomatic
and are too small to be recognized radiographically. The proximal femur was
found to be the site of metastatic lesions in 11 percent of all patients; however,
when involved, they are often likely to fracture. About 40 percent of all pathologic
fractures occur in the proximal femur. The risk of pathologic fracture is correlated
to the extent of the lesion, the type of destruction, and the anatomic location.
Lesions in high stress areas such as the lesser trochanter are very often associated
with subsequent pathologic fracture. In particular highly anaplastic and rapidly
growing vascular lesions, which are usually osteolytic, are associated with
a high risk of fracture.
Metastatic lesions that result in a net loss of bone are described as osteolytic,
as can be seen in myeloma and metastatic renal cell carcinoma. When the process
involves bone formation as observed in metastatic prostate carcinoma, the net
increase in bone results in blastic, sclerotic lesions. In cases in which there
are lytic and blastic areas, as can be seen in some metastatic breast carcinomas,
lesions are described radiographically as a mixed osteolytic osteoblastic type.
The mechanism of bone resorption is primarily osteoclast-mediated. Several known
osteoclastic stimulating factors associated with cancer play a significant role
in the process of bone resorption.
Pathogenesis of Metastes
Despite the fact that tumors originate from a single cell that lacks normal
control mechanisms, tumors consist of vast numbers of cells that are not homogeneous.
Only a limited number of cells may have the genetic potential to metastasize.
Although numerous tumor cells gain access to the systemic circulation, only
a small number of cells, probably less than 0.1 percent, survive the transport.
While random sites of metastasis can occur, selectivity of the metastatic site
depends on adhesion of molecules specific to the endothelium within the arterioles,
capillaries, and postcapillary venules of particular organs. Complementary molecules
characteristic of individual tumor types are permissive for attachment to the
specific endothelium, initiating the metastatic cascade. Organ selectivity has
been demonstrated in mice by the propensity of harvested metastatic tumor to
return, after sequential transplantation, to the organ from which it had been
harvested. The differential frequency with which human cancers metastasize to
bone presumably represents the interaction between adhesion molecules on vascular
endothelium of the skeleton and the tumor cell.
Patient Evaluation and Diagnostic Work-Up
Treatment of patients with metastatic disease requires a multidisciplinary team
approach, including the oncologist radiotherapist and orthopaedic oncologist.
Patients should be carefully analyzed based on the type of the tumor, anatomical
location and neurologic status. The diagnostic work-up needs to address and
resolve the following questions:
1. Is the lesion solitary or multifocal?
The majority of patients with bone metastases present with bone pain. Technetium
bone scanning is a good modality with which identify occult lesions that are
still asymptomatic. In relative to the cancellous portion of the bone over 40%
of bone destruction is needed before a skeletal lesion is usually identified
radiographically. When cortical bone is destroyed, however, a lesser degree
of destruction is needed for radiographic detection. A positive bone scan indicate
Mineralization as a result of osteoblastic activity. Lesions with insignificant
osteoblastic activity, such as myeloma and metastatic renal cell carcinoma,
the bone scan may be uninformative. The pattern of skeletal lesion distribution
as can be visualized with bone scans is easily recognized and highly characteristic
for skeletal metastases.
2. What is the intraosseous and extraosseous
extension of the tumor? Computed tomography (CT)
scan is helpful in assessing the size and extent of the bony destruction, while
magnetic resonance imaging (MRI) is the best modality to assess the extent of
the marrow and soft tissue extension. Malignant lymphoma may show minimal bone
destruction on plain radiography while MRI may demonstrate a large soft tissue
involvement.
3. What is the risk of pathological fracture?
Lytic processes such as metastatic thyroid, renal cell, lung carcinoma, and
malignant lymphoma involving the extremities are prone to fracture. The site
of biopsy should be selected very carefully. These patients must be protected,
bracing partial weight-bearing with crutches.
4. How vascular is the tumor? Highly vascular tumor
such as metastatic renal cell carcinoma could be associated with uncontrolled
excessive bleeding from a small open biopsy. In such cases, arteriogram embolization
should be considered preoperatively.
5. Does the tumor involve the adjacent joint?
With joint involvement consideration of resection and joint replacement should
be considered.
6. Is there a lung metastases? A chest CT scan is
done to support treatment planning. The extent of the surgical procedure will
be dependent on the overall prognosis.
7. Is it a primary tumor or metastatic tumor? The
type of surgery performed is dependent on the result of the open biopsy. In
primary tumor attempts eradicate on of the entire tumor is the goal, while in
metastatic tumors the purpose of surgery is to avoid pathological fracture and
to eliminate pain.
8. Is there a need for adjuvant therapy radiation,
chemotherapy? Prior to any surgical consideration,
the oncologist and radiation therapist should assess patients. Some patients
may be successfully treated by radiotherapy alone with dramatic diminishment
of pain. In others, patients combined treatment by radiation therapy and internal
fixation may be required.
Surgical Management
Surgical treatment should be individualized to each patient's medical circumstance
and with consideration to the anticipated impact on longevity. Good judgement
and considerable experience are necessary in the selection of patients for surgery
The patient's general condition must allow the surgical procedure to be performed
with reasonable expectation that the patient will survive long enough to benefit
from the surgery. Patients should also be informed and prepared prior to surgery
concerning realistic expectations regarding relevant issues such as functional
recovery, longevity and cure. Preoperatvely patient should be evaluated and
treated for dehydration, coagulopaties, anemia, hypercalcemia of malignancy.
The primary goals of treatment of patients with painful skeletal metastatic
lesions are to relieve pain, restore function to allow early mobilization and
to ease nursing care. It is prudent to intervene electively for impending fracture.
Pathological fracture seems to be associated with an increased incidence of
subsequent pulmonary metastases. Prophylactic fixation may reduce the incidence
of lung metastases Small lesions that do not present with an impending fracture
and are radiosensitive can be treated by radiotherapy alone to relieve pain.
Radiation may cause hyperemia at the periphery of treated bone with temporary
softening, which may increase the risk of fracture. In lesion that may progress
to impending fracture, blind intramedullary nailing with local irradiation may
give good local control with pain relief. Irradiated pathological fractures
that lack rigid fixation show a higher rate of nonunion. In a larger osteolytic
lesion, blind intramedullary nailing may not be sufficient due to mechanical
failure and telescoping migration of the bone fragments. In such cases, intramedullary
nailing supplemented by methyl methacrylate to fill the defect may give the
required fixation. In a significant number of patients with extensive destruction
affecting the joint, such as these with hip, or knee joint segmental resection,
prosthetic replacement may be indicated to allow immediate full weight-bearing.
The nature of metastatic cancer and the often poor long-term survival generally
makes long-term durability of the prosthesis unimportant.
The most common metastatic tumors arise from carcinoma of the breast, a tumor
which accounts for more than 50 percent of the cases requiring orthopedic intervention,
followed by cancers of the lung, kidney, prostate, GI tract, thyroid, and other
miscellaneous sites. In-patients. who present with metastatic cancer of unknown
primary site, the presence of bone metastases represents a sign of advanced
disease with poor life expectancy.
Metastatic Tumors to the Acetabulum
Metastatic lesions to the acetabulum should be worked-up with CT scan for better
evaluation of the extent of the lesion and to provide a guideline for the surgical
approach. Small metastatic lesions to the acetabulum may be managed by radiation
alone. Larger lesions can be treated by intralesional curettage and cement packing
followed by local irradiation. Hip joints which suffer extensive destruction
and erosion should be replaced by Endoprosthesis.
Metastatic Lesions to the Femur
Metastatic lesions to the femoral neck are best treated by a bipolar prosthesis.
Metastatic disease to the trochanteric region can be treated by intralesional
curettage and cement packing, supplemented by pin and plate fixation In cases
with pathologic fracture, proximal femur replacement may be indicated. Impending
fractures of the femoral shaft are best treated by closed intramedullary nailing.
In cases with a large bony defect, augmentation by a cement spacer to prevent
telescoping may achive a good result. Metastatic disease to the femoral condyle
may be treated by intralesional curettage and cement packing. In those cases
where there is pathologic fracture, distal femur replacement may be indicated.
Metastatic Lesions to the Scapula and Upper Extremity
Conservative treatment for pathologic fracture of the humerus is often associated
with persistent pain and shoulder stiffness. To provide immediate pain relief
and restore shoulder mobility, internal fixation is recommended. Metastatic
lesion to the scapula can be treated by partial or total scapulectomy. Pathologic
fracture of the humeral head is best managed by Endoprosthesis replacement.
In fractures of the humeral shaft blind intramedullary nailing is the acceptable
approach. In those cases with large defects, the fixation should be augmented
by methyl methacrylate. Radiation can be delivered 2 weeks after surgery. Metastatic
lesions of the radius and ulna are best stabilized by an intramedullary pin.
Metastatic Lesions to the Spine
The vertebral bodies are the most common site for metastatic lesions. Most vertebral
metastases initially are occult and painless. The majority can be detected on
routine bone scan. Metastatic lesions that do not compromise stability may remain
asymptomatic. Pain typically occurs when a significant amount of bone destruction,
has occurred leading to microfractures. Pathologic fractures of the vertebral
bodies are of a compressive type and are usually stable. Patients with metastatic
disease to the spine commonly develop back pain before any neurologic sequelae.
MRI scan has essentially replaced myelography as the method of choice to demonstrate
local extension and extradural compression. Spinal cord compression at the level
of the thoracic spine can cause hyperreflexia and spasticity with complete paraplegia.
A radiosensitive metastatic condition, such as lymphoma, may be treated effectively
by irradiation therapy. Surgical decompression may be indicated in those patients
who do not respond to radiation therapy, and subsequently develop neurologic
deterioration. Surgical treatment for metastatic conditions to the spine has
improved significantly with the introduction of new surgical techniques and
instrumentation. The result of anterior spinal decompression with vertebral
body resection, replacement by a cement spacer, and bracing has proved to be
very effective in stabilizing the spine and preventing further neurologic deterioration.
Hypercalcemia of Malignancy
Hypercalcemia associated with skeletal metastases is a common metabolic complication
and a life-threatening disorder. The clinical symptoms associated with hypercalcemia
are weakness, nausea, vomiting, dehydration, polyuria, anorexia, lethargy, confusion,
stupor, and coma. Hypercalcemia is most commonly associated with myeloma or
carcinoma of the breast, but it may also occur with renal, ovarian, and lung
cancers, as well as other neoplasms. Hypercalcemia is related to the capacity
of the tumor to secrete specific hypercalcemic factors and usually not to increased
intestinal absorption of calcium. The two major mechanisms for cancer-related
hypercalcemia are local osteolytic factors and systemic factors. The local osteolytic
factors cause osteoclast-mediated bone resorption and destruction. Tumor cells
and inflammatory cells produce osteoclast-activating factors including cytokines
such as interleukin 1, tumor necrosis factors, transforming growth factors,
and prostaglandin. Hypercalcemia in patients with metastatic breast carcinoma
is most commonly associated with widespread skeletal disease. Multiple myeloma
is associated with extensive bone destruction often leading to bone pain, pathologic
fracture, and hypercalcemia.
Systemic factors for hypercalcemia may be unassociated with localized bone disease.
This condition is characterized by the production of circulating hypercalcemic
factors, the tumor being the secretary gland and the target organ being the
Osteoclasts in the skeleton. The clinical syndrome is due to the production
of parathyroid-like hormone (PTH). Systemic PTH-like mediated hypercalcemia
is common in Squamous cell carcinoma, and renal, bladder, and ovary carcinoma.
Occasionally, patients with various types of lymphomas develop hypercalcemia,
the pathogenesis of which is not fully characterized. In part, the condition
could be related to the production of bone-resorbing lymphokines by the lymphoid
cells. In some patients, hypercalcemia could be related to increased 1,25-dihydroxyvitamin
D produced by lymphoid cells, and in these cases is likely associated with increased
intestinal absorption of calcium. Myeloma cells produce cytokines that activate
osteoclastic bone resorption.
Treatment of hypercalcemia should include restoration of intravascular volume
by saline infusion to correct dehydration and to increase urinary excretion
of calcium. Dietary restriction of calcium plays a small role only in those
patients who have increased intestinal absorption. Calcium and vitamin D supplements
should be discontinued. After the blood volume has been restored, administration
of bisphosphonate such as pamidronate or etidronate inhibits osteoclastic bone
activation. Calcitonin, which also inhibits osteoclast-mediated bone resorption
and enhances urinary calcium excretion, may be useful for emergencies. Previous Page
