Intractable back pain is a frequent symptom of disseminated
cancer, and in patients who have spinal metastases the pain is related
to spinal instability13. The spinal instability is mechanical and
is related to extensive bone destruction due either to tumor-mediated
osteolysis or to iatrogenic causes, and the pain is due to vertebral
fracture. Cancer of the breast is the most common primary tumor
associated with metastases to the spine (Table II)17. However, any tumor can metastasize
to the spine and produce sufficient destruction to render the spine
unstable, leading to excruciating pain that is induced by mechanical
instability and to spinal-cord or nerve-root compression resulting
in paresis. When the pain is excruciating, the patient is comfortable
only when lying absolutely still. Any movement, including log-rolling
(even by two or three trained nurses), is associated with agonizing
pain, and the patient may not be able to sit, stand, or walk because
of the pain, even with use of a spinal orthosis. When the spine
is minimally involved, the patient may be relatively free of pain when
wearing a rigid spinal orthosis, but any movement of the back (for
example, turning in bed, sitting, or standing) may be impossible
without the orthosis.
Plain radiographs show destruction of the vertebral body with
minimal-to-complete vertebral collapse. It is unusual to see a discrete
fracture. Nevertheless, the bone destruction in the vertebral body
should be considered equivalent to a pathological fracture of an
appendicular bone because the pain is due to a pathological fracture
that creates mechanical instability and not to the metastases22.
Neither radiation therapy nor chemotherapy, even if successful in
controlling the tumor, will alleviate the pain. As in the treatment
of pathological fractures of the long bones, stabilization of the
vertebral segments is required for pain relief. The spine can be
stabilized with either an anterior or a posterior approach5,7-9,12,15,20-22,31,32.
Vascular metastatic lesions necessitate preoperative embolization,
particularly if anterior stabilization is being considered18. This
is particularly relevant with regard to metastases from renal carcinoma;
however, other tumors also may be very hyperemic.
Compression of the spinal cord or the cauda equina has been commonly
treated with laminectomy and decompression. The tumor usually involves the
anterior elements, and laminectomy may destabilize a spine that
has been weakened as a result of tumor-induced bone destruction.
Studies have shown that radiation therapy combined with steroids
is at least as effective as laminectomy6,11,19. Because of the risk
of subsequent instability, it is recommended that the spine be stabilized
at the time of decompression14,23,24,33. The decompression can be
carried out anteriorly or posteriorly, but it is essential that
posterior decompression be combined with stabilization of the spinal
segments to avoid the development of progressive kyphosis, which
may induce additional compression of the spinal cord and neurological impairment.
Laminectomy alone is contraindicated because it results in spinal
instability. Removal and replacement of the lamina has been described10.
Operative treatment should be combined with a short course of high-dose
steroids to minimize any postoperative edema and by a course of
postoperative radiation therapy.
Initially, the Harrington rod was the only instrumentation available
for spinal stabilization. It soon became apparent that the fixation
provided by this device was inadequate despite the hooks being embedded
in methylmethacrylate and that, if a posterior approach was to be
used, some form of segmental fixation was also necessary. Several types
of instrumentation were subsequently developed, all of which rely
on fixation at multiple levels that include at least three vertebrae
cephalad and three vertebrae caudad to the level of involvement.
The Banks-Dervin rod, a one-centimeter square rod with multiple
screw-holes, is contoured to the shape of the spine and is placed
in the gutter between the spinous process and the lamina, often with
use of methylmethacrylate as a grout; it then is fixed with screws
that pass beneath the spinous process dorsal to the neural elements
and into the contralateral lamina. Double Luque rods and the Hartshill
rectangle are attached to the vertebrae with sublaminar wires. When
the lumbar spine is stabilized the instrumentation is contoured
to provide lumbar lordosis, and when the thoracic spine is stabilized
the instrumentation is contoured to provide dorsal kyphosis.
If posterior fixation is inadequate for stabilization of the
spine in patients with metastatic lesions in the fourth and fifth
lumbar vertebrae, an anterior stabilization procedure also is performed.
Newer methods of instrumentation whereby the rods can be fixed with
interpedicular screws, hooks, or wires have recently become available.
We used one such instrumentation system, the Isola device (DePuy
AcroMed, United Kingdom), in our patients. Patients with localized
metastatic lesions have been treated with anterior stabilization
with use of the Kaneda device, which initially was supplemented
with methylmethacrylate and more recently has been augmented with
a vertebral replacement cage.
In a series of eighty patients, we found an overall referral
rate of approximately four patients per year. This is a much lower
rate than would be expected from the prevalence of metastatic disease
to the spine reported by one of us (C. S. B. G.) and Sylvester13.
Thus, a study was undertaken to determine whether patients who had
a metastatic lesion in the spine were being appropriately diagnosed
and referred for treatment.
Because cancer of the breast accounted for approximately half
of the patients who had spinal instability secondary to metastases,
we decided to review the records of all patients who had been treated
for breast cancer in a single region in the United Kingdom. We examined
the records of patients in one region rather than those of patients who
had been treated in a particular hospital because referral patterns
may differ from one hospital to another. Since it takes some time
for skeletal metastases to become manifest, it also was decided that
patients would be evaluated seven years after the diagnosis of breast
cancer had been confirmed. As it was assumed that many patients
had died from the breast cancer during this seven-year period, a
retrospective analysis was conducted of the medical records. The
vast majority of patients had been referred to the regional cancer
hospital for radiation therapy after primary treatment had been obtained
at their local hospital. Subsequent follow-up often had been performed
at the regional cancer hospital and the local district general hospital,
and the records from both hospitals were reviewed and matched for
each patient.
A total of 1412 women were diagnosed with and treated for breast
cancer in thirty-one hospitals in the survey area. Of these patients,
963 had complete records, which were used for analysis. The remaining
notes either had been destroyed or were incomplete. Analysis of
the records showed that, at seven years, 499 (52 percent) of the
963 women had died from breast cancer. Overall, 420 (44 percent)
of the 963 patients had complained of bone pain at some time during
the seven years after the initial diagnosis of breast cancer. Of
these 420 patients, 207 (21 percent of the 963) had proven skeletal
metastases whereas 213 (22 percent) had a benign etiology (such
as arthritis) for the bone pain. Of the 207 patients who had skeletal
metastases, 89 percent died compared with 36 percent of the 213
patients who had nonmetastatic bone pain. Only forty-five (22 percent)
of the 207 patients who had painful skeletal metastases were referred
to an orthopaedic surgeon for evaluation and treatment.
A large number of patients had complications as a consequence
of structural lesions. Of the 207 patients who had bone metastases,
eighty-eight had one to five complications and several had more than
one complication (Table I). Many patients were treated nonoperatively,
including those who were considered to have terminal breast cancer.
The difference in the referral patterns between patients who had
sustained a pathological fracture of the femur and those who had
spinal instability was dramatic. All twenty-two patients who had
a pathological femoral fracture were referred for an orthopaedic
opinion. Nineteen were treated operatively, and three who were thought
to have end-stage cancer were treated nonoperatively. Only six of
fifty-one patients who had spinal instability were referred for
an orthopaedic opinion. None of these patients had operative treatment.
The results of this study suggest that spinal instability due
to metastases develops within seven years in 5 percent of patients
who have breast cancer and that patients who have spinal instability secondary
to metastatic disease are not being referred for treatment. Similar
results were reported by O'Donoghue et al.29,30, who evaluated 269 consecutive
patients with breast cancer who had been seen in an internationally
known breast unit. Those authors found that patients who had a pathological
fracture did better after operative intervention combined with adjunctive
therapy than did those who had nonoperative treatment alone. Forty-seven
women had a total of eighty-two instances of structural bone destruction,
fifty-two (63 percent) of which involved the spine and eleven of which
were associated with cord compression. The average duration of symptom-free
survival was thirty-nine weeks in the group that had been treated
operatively compared with eleven weeks in the group that had been
treated nonoperatively, and the average duration of overall survival
was twenty-two and nine months, respectively (p < 0.05 for both
comparisons). O'Donoghue et al. stated that clinical review by an
orthopaedic surgeon would have been appropriate in 89 percent of the
instances but was sought in only 46 percent and that operative intervention
was feasible in 65 percent but was performed in only 31 percent.
The failure to refer patients who have spinal instability secondary
to metastatic disease of the spine suggests that the education of
breast surgeons, oncologists, radiation therapists, and others involved in
the treatment of patients who have advanced cancer has been incomplete.
In order to determine the reasons for the lack of dissemination
of information on the treatment of metastatic disease of the spine,
we reviewed textbooks on oncology, breast cancer, general surgery, and
orthopaedic surgery found in our university library, the library
in the regional cancer hospital, and the library of our teaching
hospital. Although most of the textbooks mentioned skeletal metastases,
only two of nine oncological textbooks, one of twelve textbooks
on breast cancer, one of eleven textbooks on general surgery, and,
disappointingly, only five of eight textbooks on orthopaedic surgery
even mentioned spinal instability secondary to metastatic disease
of the spine.
In 1995, the European Journal of Surgical Oncology published
a supplement on the treatment of symptomatic breast disease4. The
supplement was thirteen pages long, with a double-column format; however,
in the objectives that were cited there was no mention of bone pain.
Fifty-four centimeters of text was devoted to the management of
metastatic disease. The only reference to bone metastases was included
in the phrase "palliative measures, such as radiotherapy for bone
metastases, bone stabilisation by orthopaedic surgery, pleurodesis,
etc." Similar guidelines developed by the European Society of Surgical
Oncology1, based on the guidelines developed by the British Association
of Surgical Oncology and the Danish Breast Cancer Cooperation Group,
contained no mention of skeletal metastases or associated complications.
Recently, the British Association of Surgical Oncology updated
its guidelines, which now include the phrase "radiotherapy for bone
metastases, and bone stabilisation by orthopaedic surgery (see the forthcoming
BASO Guidelines for the Management of Bony Metastases)."2 It was
therefore extremely disappointing to note that the Association's
guidelines on the management of metastatic bone disease in the United
Kingdom, which are twenty-one pages long and include three pages
devoted to the use of bisphosphonates, do not contain a subsection
on metastases to the spine3. Spinal instability was mentioned as
a complication of spinal metastatic disease, and patients most likely
to benefit from operative intervention were described as those in
whom "pain [was] exacerbated by movement and relieved on rest (spinal
instability)." The guidelines also suggested that patients who have
pain and destruction of more than 50 percent of the vertebral body
should have an immediate neurological examination and, in the absence
of neurological signs, should be evaluated by an orthopaedic surgeon
prior to being considered for radiation therapy3.
The British Medical Journal, in a review article
on myeloma34, published a radiograph that was suggestive of spinal instability16,26.
The caption to the radiograph was: "Bone pain from mechanical effects
of myeloma damage (as in spine shown here) often necessitates long-term
treatment with strong analgesia despite response to chemotherapy."
The reader might ask why the editor accepted this article, which
made no mention of operative stabilization of the spine despite
the publication, for more than fifteen years, of reports on the
need for stabilization and its efficacy5,7,8,12,14,15,17,20,22,25,31,32.
In ABC of Breast Diseases, neither spinal instability
nor spinal stabilization for metastatic disease of the spine was mentioned27,28.
However, it was stated that "cord compression is not usually amenable
to surgery" and that "patients with isolated metastases causing cord
compression who are fit can be treated by emergency laminectomy,"
even though laminectomy should never be carried out in a patient
who has metastatic disease of the spine unless the procedure is
combined with stabilization. Laminectomy alone further destabilizes
a spine that is already compromised by metastatic bone destruction.
Finally, we reviewed the practices of consultant neurosurgeons,
consultant orthopaedic surgeons who did not have a particular interest
in spinal operations, and consultant orthopaedic surgeons who did
have such an interest. These practitioners were asked whether they
would treat cord compression with laminectomy alone and whether
they would simultaneously stabilize the spine in a patient who had
skeletal metastases and spinal instability. Fifty-nine (78 percent)
of seventy-six neurosurgeons indicated that they would consider
a laminectomy, although most said that they would perform a decompression
with stabilization. Several neurosurgeons indicated that they would
perform only a laminectomy in a patient who was unfit for a more major
procedure such as stabilization. Eleven (15 percent) of seventy-five
orthopaedic spinal surgeons said that they would consider only a
laminectomy. Fifty-three (79 percent) of sixty-seven spinal surgeons
said that they would stabilize the spine in the presence of spinal
instability; three (4 percent), that they would refer the patient
to a neurosurgeon; and eleven (14 percent), that they would not
consider operative intervention but would refer the patient to an
oncologist or a radiation therapist. Thirteen (6 percent) of 208
general orthopaedic surgeons indicated that they would perform a
laminectomy for the treatment of cord compression, and fifty-four
(26 percent) said that they would refer a patient who had spinal
instability to an oncologist or a radiation therapist and not to
a spinal surgeon or a neurosurgeon.
In conclusion, studies show that spinal instability is a common
complication of skeletal metastases, occurring in at least 5 percent
of patients who have breast cancer. Breast cancer accounts for approximately
half of patients who have spinal instability secondary to metastatic
cancer, with multiple myeloma being the next most common cause.
Spinal instability is associated with considerable morbidity. The
symptoms can be relieved by decompression and spinal stabilization,
and many patients remain pain-free for several years after operative intervention.
The combination of operative intervention with radiation therapy
(if feasible) and endocrine therapy or chemotherapy, or both, not
only gives patients with these lesions a better quality of life
but also is associated with a longer life expectancy than is associated
with nonoperative treatment alone. However, our review suggests
that only a very small number of patients whose quality of life
could be improved by appropriate operative treatment are being referred
for such treatment.
Principles of Evaluation and Treatment
We reviewed our treatment of patients who had spinal instability
secondary to metastatic disease of the spine. All of the patients
required preoperative assessment to determine their fitness for
operative intervention. This assessment included skeletal scintigraphy
to evaluate the extent of skeletal dissemination of the disease.
Preoperative magnetic resonance imaging was indicated to demonstrate
not only the extent of skeletal involvement throughout the spine
but also the presence of any extradural tumor.
Whenever possible, the patients received postoperative irradiation.
However, some patients had received the maximum tolerable dose preoperatively.
The spinal cord is sensitive to radiation, and any additional radiation
therapy increases the risk of transverse myelitis. The underlying tumor
was treated with endocrine therapy or chemotherapy, depending on
the type of primary tumor. If there are other small skeletal metastases, bisphosphonates
may be indicated, particularly if the primary tumor is breast carcinoma
or if the patient has multiple myeloma; however, bisphosphonates
are not indicated for large lytic metastatic lesions.
Clinical Data
The senior author (C. S. B. G.) has treated eighty patients who
had spinal instability secondary to metastatic disease (Table II)17. Forty patients
had cancer of the breast; ten, multiple myeloma; six, cancer of
the kidney; four, cancer of the lung; four, cancer of the prostate; two,
melanoma; and two, cancer of the cervix. The remaining twelve patients
had different types of cancer.
Thirty-four of the eighty patients had clinical evidence of compression
of the spinal cord or the cauda equina and weakness of the lower
extremities severe enough to affect walking or standing; the symptoms
sometimes were associated with loss of bladder function. These patients
were treated with decompression at the time of stabilization. Twenty-three
(68 percent) of the thirty-four patients recovered neurological
function to the extent that they could walk without orthoses and
bladder function, if it had been compromised, returned to normal.
It must be emphasized, however, that these patients presented primarily
with pain due to spinal instability. In two patients, cord compression
recurred at ten and fourteen months after decompression.
All eighty patients had decompression and spinal stabilization
with use of a variety of spinal instrumentation systems (Table III)17. The most
frequently used device was the Hartshill rectangle (thirty-one patients),
followed by the Banks-Dervin rod (twenty-six patients).
Results
Seventy-one (89 percent) of the eighty patients had complete
relief of pain, and four patients (5 percent) had partial relief
(Table IV)17.
Five patients had failure of the treatment. One of these patients
died of septicemia after a wound infection. Another patient had
an infection, requiring removal of the implant. Two patients, in
whom we had used Harrington rods and hooks, had loosening of the
implant. In the fifth patient, who had complete relief of pain,
paraplegia developed as a result of an extradural bleed despite
removal of the clot. He had previously received anticoagulants for
the treatment of an intercurrent illness. Preoperative radiation
therapy predisposed to infection.
The first patient in our series had multiple myeloma and had
been treated with chemotherapy and radiation therapy. Nevertheless,
he was unable to sit up or walk and was confined to bed because
of excruciating back pain. Even log-rolling by two trained nurses
was painful. At the time that he was evaluated, the only device
that was available to stabilize the spine was the Harrington rod.
The thoracic spine was stabilized with two Harrington rods, and
the hooks were cemented in situ with methylmethacrylate.
Even though one hook loosened, the patient had total relief of pain
to the extent that he could walk and could return home. Eight months
later, he was readmitted to the hospital with clinical signs of
cord compression. The instrumentation had to be removed at the time
of decompression of the spinal cord.
It is now a routine practice to evaluate the spinal canal and,
if there is any tumor within the canal, the spinal cord or the cauda
equina, depending on the level of involvement, is decompressed at
the site of involvement at the time of stabilization. In the initial
years of our series, the spinal canal was evaluated with myelography;
later, it was evaluated with myelography combined with computerized
tomography; and currently, magnetic resonance imaging is used. The
decompression is carried out prior to stabilization; if the tumor
is localized to one vertebral level and it is mainly anterior, anterior
decompression and stabilization is performed, and if the tumor extends
over several vertebral levels, posterior decompression and stabilization
is carried out. Once the decompression is performed, the spine is
stabilized irrespective of whether the patient has neurological
signs or symptoms or whether there is tumor within the canal. Anterior
decompression and stabilization is now more commonly carried out.
Complications
There were several complications in the seventy-one patients
(89 percent) who had relief of pain. Two patients, both of whom
had had preoperative radiation therapy, had wound breakdown. In
one of these patients, secondary closure was successful; the other
patient required skin-grafting with use of a flap. Another patient,
who also had had preoperative radiation therapy, had a wound infection,
which was treated successfully with antibiotics. This led us to
conclude that patients with spinal instability or neural compression
who require operative intervention should not receive preoperative
radiation therapy. However, postoperative radiation therapy should
be given whenever possible.
The instrumentation failed in two patients. In one patient who
had myeloma (the only patient in whom two Luque rods were inserted),
one rod broke and the patient required anterior bone-grafting. Twelve
years after the procedure, the patient was alive and active, without
a recurrence of compression of the cauda equina or pain due to spinal instability.
In another patient, the instrumentation (a Hartshill rectangle)
fractured after five years of complete relief from pain.
Several patients lived for many years after the spinal stabilization.
One patient who had multiple metastases to the spine from breast
cancer responded well to tamoxifen, which was given after the performance
of spinal decompression and stabilization for the treatment of spinal
instability associated with compression of the cauda equina. Five
years after the procedure, she was in a motor-vehicle accident and
sustained an undisplaced fracture of the odontoid process, which
healed with nonoperative treatment. A year later, she had additional
spread of the cancer and did not respond to chemotherapy. She died
six and a half years after the spinal stabilization, without any
recurrence of the back pain or neural compression.
Results similar to those in our series17 have been reported by
other authors. Onimus et al.31 reported the results of operative
intervention in 100 patients who had spinal metastases. Anterior stabilization
was performed in fifty-eight patients; posterior stabilization,
in thirty-three; and combined anterior and posterior stabilization,
in nine. Preoperatively, ninety-six patients had vertebral pain,
and forty-three had radicular pain. Patients who had metastases
from lung cancer had intractable pain. Walking was impossible for
fifty patients, either due to neural compression or to pain caused
by the spinal instability. Thirty-five (70 percent) of the fifty
patients were able to walk after decompression and stabilization.
Of thirty-eight patients with a neurological deficit preoperatively,
thirty had a decrease of the deficit postoperatively. Sixty-two
patients stopped using analgesics after the operation. Overall,
there was clinical improvement in eighty of the 100 patients.
Our review shows that only a very small percentage of patients
who have spinal instability secondary to metastatic disease of the
spine are being referred to the appropriate specialists in a timely manner.
We believe that oncological education in terms of the management
of patients who have spinal instability secondary to metastatic
cancer has failed, probably for many reasons:
1. Breast surgeons apparently do not have a specific awareness
of how to manage bone pain in their patients.
2. Oncologists and radiation therapists are not kept up to date
on the role of modern orthopaedic surgery and what it can offer
their patients.
3. The editors of broad-spectrum journals such as the British
Medical Journal fail to understand the subject of spinal
instability, make poor selections with regard to authors and reviewers,
and often refuse to publish articles aimed at the general medical
profession because they consider the topic of spinal instability
to be too specialized.
4. Courses on breast cancer do not cover the orthopaedic management
of patients with this disease.
5. The vast majority of textbooks on breast cancer, oncology,
and general surgery do not mention spinal instability secondary
to metastatic disease of the spine, and even textbooks on orthopaedic
surgery fail to include this complication.
6. Specialized journals, such as The Journal of Bone
and Joint Surgery, are not read widely by physicians in
other disciplines, who therefore remain unaware of recent advances
in the treatment of spinal instability.
7. Some neurosurgeons still perform a laminectomy without stabilization
in patients who have metastatic disease of the spine.
8. Some orthopaedic surgeons perform similar inappropriate procedures,
and others fail to refer patients for decompression and stabilization.
As orthopaedic surgeons, we have failed to educate our colleagues
in other specialties about the principles of the management of spinal
instability secondary to metastatic disease of the spine.
What is the future for the management of metastatic disease of
the spine? We believe that the only solution is for large orthopaedic
departments to establish bone-pain clinics for patients who have metastatic
cancer so that they can be evaluated adequately. Then, if a patient
required operative intervention for a complication secondary to
skeletal metastases, it would be carried out by the appropriate
orthopaedic surgeon in that department. Treatment based on the site
of involvement would include spinal stabilization with or without
decompression by the spinal surgeon, proximal femoral replacement
with or without acetabular reconstruction by the hip surgeon, fixation
of pathological fractures by the trauma surgeon, and so on. The
development of such clinics would do much to improve the quality
of life of patients who have skeletal metastases and should also
raise the profile of orthopaedic surgery among all doctors involved
in the treatment of patients who have malignant disease.
Note: The authors are grateful to the Centre for Cancer Epidemiology,
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