You are on page 1of 15



Spinal metastasis is common in patients with cancer. The spine is the third most
common site for cancer cells to metastasis, following the lung and the liver. Approximately
5-30% of patients with systemic cancer will have spinal metastasis; some studies have
estimated over 30-70% of patients with a primary tumor have spinal metastatic disease at
autopsy. Spinal metastases are slightly more common in men than in women and in adults
aged 40-65 years than in others. Fortunately, only 10% of these patients are symptomatic,
and approximately 94-98% of those patients present with epidural and/or vertebral
involvement. Intradural extramedullary and intramedullary seeding of systemic cancer is
unusual; they account for 5-6% and 0.5-1% of spinal metastases, respectively.

Metastatic disease to the neuraxis other than the brain parenchyma and the spinal column
is uncommon. The incidence of cancer cells invading the leptomeninges is about 8-13%. In
autopsy studies, the rate has been estimated to be 25%.

Spread from primary tumors is mainly by the arterial route. Retrograde spread
through the Batson plexus during Valsalva maneuver is postulated. Direct invasion through
the intervertebral foramina can also occur. Besides the mass effect, an epidural mass can
cause cord distortion, resulting in demyelination or axonal destruction. Vascular
compromise produces venous congestion and vasogenic edema of the spinal cord,
resulting in venous infarction and hemorrhage.

About 70% of symptomatic lesions are found in the thoracic region of the spine,
particularly at the level of T4-T7. Of the remainder, 20% are found in the lumbar region and
10% are found in the cervical spine. More than 50% of patients with spinal metastasis have
several levels of involvement. About 10-38% of patients have involvement of several
noncontiguous segments. Intramural and intramedullary metastases are not as common as

those of the vertebral body and the epidural space. Isolated epidural involvement accounts
for less than 10% of cases; it is particularly common in lymphoma and renal cell carcinoma.
Most of the lesions are localized at the anterior portion of the vertebral body (60%). In 30%
of cases, the lesion infiltrates the pedicle or lamina. A few patients have disease in both
posterior and anterior parts of the spine.

Primary sources of spinal metastatic disease include the following:

Lung - 31%
Breast - 24%
GI tract - 9%
Prostate - 8%
Lymphoma - 6%
Melanoma - 4%
Unknown - 2%
Kidney - 1%
Others including multiple myeloma - 13%

Median survival of patients with spinal metastatic disease is 10 months.
The morbidity of spinal metastatic disease is important, especially in patients with
paralysis and/or bowel and bladder involvement. The latter compromises the quality of life
of patients with cancer and puts an additional burden on their caregivers. Cord compression
is normally seen as preterminal event. Median survival at that stage is about 3 months.

Spinal metastasis may be the initial presentation in 10% of patients with systemic
cancer. About 2% of symptomatic patients have no identifiable systemic disease.
Approximately 90% of patients with spinal metastasis present with bone and/or back pain,
followed by radicular pain. Bone pain at night in a patient with systemic cancer is always an
ominous symptom. In fact, it is the most ominous symptom in patients with metastatic
disease to the spine. Not all spinal metastasis result in neurological deficit, only 50% of
these patients have sensory and motor dysfunction, and 50% have bowel and bladder
dysfunction. A small group of (5-10%) of patients with cancer present with cord
compression as their initial symptom. Among those who present with cord compression,
50% are nonambulatory at diagnosis, and 15% are paraplegic. Cord compression is
commonly seen as a preterminal event in cancer patients.

Imaging Studies
Diagnostic procedures in evaluation of spinal metastatic disease
Thorough metastatic workup is paramount in patients with spinal metastasis. This helps to
delineate the nature and the extent of the systemic disease. However, the appropriateness
of diagnostic tests depends on the time available. In patients with rapidly progressing
symptoms, chest radiography and physical examination is all that is warranted. Plain
radiography and, whenever possible, a CT of the entire spine should then be performed,
followed by MRI with and without contrast enhancement.
Plain radiography is used to show erosion of the pedicles or the vertebral body. Owleye erosion of the pedicles in the anteroposterior (AP) view of lumbar spine is characteristic
of metastatic disease and is observed in 90% of symptomatic patients. However, radiologic
findings become apparent only when bone destruction reaches 30-50%. Osteoblastic or
osteosclerotic changes are common in prostate cancer and Hodgkin disease; they are
occasionally seen in breast cancer and lymphoma.
CT scanning is useful in determining the integrity of the vertebral column, especially
when surgery is anticipated. CT myelography is used if MRI is not available. CT also allows
for an examination of paraspinal soft tissues and paraspinal lymph nodes.[1]

Emergency myelography is still used in situations where an MRI is not available. The
advantage of an MRI is its noninvasive nature, whereas myelography allows for
cerebrospinal fluid (CSF) sampling. CSF sampling should be deferred if evidence of nearcomplete or complete spinal block is noted. The risk of neurologic deterioration after
myelography is about 14% but is less likely with C1-2 puncture.
With MRI, the sagittal scout image is used for rapid screening of the entire spinal
axis and its surrounding soft tissues. MRI is the imaging modality of choice. Contrastenhanced fat-suppressed images help to differentiate metastasis from degenerative bone
marrow. Diffusion-weighted images distinguish metastasis from osteoporotic bone.
Osteoporotic fractures are hypointense, and metastases are hyperintense. See the image

Spinal metastasis.
Bone scanning
Bone scans are positive in 60% of patients but they are not specific.
Lesions that activate bone metabolism increase technetium-99m uptake.
Nuclear studies are useful to determine cancer burden and are effective in scanning
the entire axial and appendicular skeleton. The use of single photon emission CT (SPECT)
and positron emission tomography (PET)CT allow for rapid screening and staging of
systemic disease. In many ways, this PET-CT is a standard modality to stage systemic
disease and tumor burden, and it is extremely useful in guiding the aggressiveness of
surgical management of metastatic disease to the spine.

Medical Care
No treatment has been proven to increase the life expectancy of patients with spinal
metastasis. The goals of therapy are pain control and functional preservation. The most
important prognostic indicator for spinal metastases is the initial functional score. The ability
to ambulate at the time of presentation is a favorable prognostic sign. Loss of sphincter
control is a poor prognostic feature and mostly irreversible. Other problems associated with

metastatic disease include pain related to pathologic fractures, hypercalcemia, and

psychological problems.

Treatment decisions for patients with spinal metastases can be challenging, and
survival prognosis should be considered when determining the best course. In a
retrospective study, Wibmer et al examined prognostic scoring systems (Bauer, Bauer
modified, Tokuhashi, Tokuhashi revised, Tomita, van der Linden, and Sioutos) in 254 spinal
metastases patients.[2] The Bauer and Bauer modified scores were better predictors of
survival. Factors associated with better prognosis with survival of more than 3 months and
improved quality of life included location of the primary tumor, extent of visceral metastases,
and systemic chemotherapy adverse effects.

This discussion focuses on the management of pain, structural stability, local disease, and
hypercalcemia. Medical management that addresses the systemic disease, such as
chemotherapy and hormonal therapy, are not discussed. Hormonal manipulation, such as
the use of tamoxifen to treat breast cancer, preserves bone mineralization because of its
estrogen-agonistic effect.

Treatment of pain
Patients with spinal metastasis commonly have bone pain. Their pain may be related
to bone destruction or pathologic fractures. Local pain is due to stretching of the periosteum
and may respond to irradiation. Axial pain can occur when vertebral compression and/or
collapse occurs. Axial pain is secondary to mechanical instability. It causes distress and
reduces mobility of the patients. In addition, a number of these patients have neuropathic
pain. This pain may be related to root irritation and/or meningeal irritation secondary to
cancer infiltration. Both steroids and nonsteroidal anti-inflammatory drugs (NSAIDs) are
commonly used to manage bone pain. Use of spinal orthotics and physiotherapy are useful
adjuvant therapies for this group of patients.

Steroid therapy is effective in treating bone pain. Immediate treatment is high-dose

dexamethasone. The optimal dose has not been established. However, in practice, the
usual dose is a loading dose of 10 mg then 4 mg every 6 hours. Of all the corticosteroids,
dexamethasone has the least mineralocorticoid effect and is least likely to be associated
with infection or cognitive dysfunction, though it does increase the risk of myopathy. Other
adverse effects include psychotic reaction (5%), GI bleeding (< 1%), and glucose
intolerance (19%).

The frequency of complications from steroid therapy depends on the duration of the
treatment and is associated with hypoalbuminemia. Treatment lasting more than 3 weeks is
more likely to be associated with complications. Hypoalbuminemia appears to increase the
risks of adverse effects associated with steroid treatment.

In about 70-80% of patients, symptoms improve within 48 hours of treatment.

Approximately 64% of patients report alleviation of pain within 24-48 hours of starting
steroid therapy, and 57% report improvement in their motor function. In most patients,
steroid use must be continued until radiotherapy is completed.

Treatment of neuropathic pain

Emerging evidence shows that antiepileptic drugs are effective in treating pain.
Gabapentin is frequently used to treat neuropathic pain and is well tolerated. Other drugs,
such as lamotrigine, carbamazepine, levetiracetam, tiagabine, and topiramate have also
been used; tricyclic antidepressants are still being used to treat neuropathic pain. However,










Topical preparations, such as the lidocaine patch, are less effective than the drugs
previously mentioned. Opioid analgesic is useful. The concern about addiction and
tolerance with long-term use should not be a major concern in patients with cancer.
Chemical epidural neurolysis was infrequently used to treat medically intractable pain. It is

effective for interrupting single or multiple radicular pains, but it poses a risk of acute
deterioration especially when structural instability or compression is present.

Neurosurgical ablation, such as rhizotomy, is indicated in patients with severe sacral

pain and bowel and bladder involvement. It involves major surgery and is not commonly
done. Likewise, spinothalamic tractotomy or cordotomy are not commonly used to treat
spinal metastatic diseases.

Radiation therapy is also effective in treating pain caused by bone metastasis. A

detailed discussion of this modality and its use in treating spinal metastatic disease is
discussed in the following section.

Hypercalcemia is particularly common in patients with lytic metastasis, and it is not
infrequently found in those with paraneoplastic syndrome that produces parathyroid
hormonerelated protein. Patients with hypercalcemia commonly present with polyuria, and
some, with pre-renal failure. Initial treatment should be rehydration and administration of a
steroid. Bisphosphonate is useful to control the lytic process. It inhibits osteoclast function,
decreasing bone resorption.

Surgical Care
General considerations in controlling local disease
Radiotherapy and now surgical radical resection (spondectomy) are the preferred
treatments to control local disease.

Radiation therapy is more effective in achieving pain control (67%) than surgery
(36%). Of note, surgery alone is the least effective way to treat spinal metastases. About
20-26% of patients who undergo surgery have further deterioration in terms of mobility or

sphincter control, whereas 17% of those receiving radiation therapy have further

The advancement of minimally invasive surgery and of new forms of robotic radiation
therapy has radically changed the management paradigm of metastasis disease to the
spine. Current thinking is to perform early radical resection of a single lesion in the spine
and to administer adjuvant stereotactic radiation therapy to eradicate the disease. This
approach allows for decompression, stabilization, and suppression of local recurrence.

Indications for surgery and radiotherapy

The traditional treatment for spinal metastasis is radiation, steroids. In rare cases,
surgery is advocated as a last resort.

Radiotherapy remains the mainstay of treatment for spinal metastatic disease. Most
of lymphoreticular tumors and prostate carcinoma are relatively insensitive; lung and breast
are relatively insensitive. Tumors of the GI system and kidney are resistant to radiotherapy,
as are melanomas. Nevertheless, radiotherapy elicits some response in melanomas. About
80% of patients with pretreatment pain have symptomatic relief; 48% of patients with motor
or sphincteric dysfunction respond to treatment.
The common regimen is 30 Gy in 10 fractions. The amount of radiation is empirical
and based on the therapeutic ratio, a function of the fractionation dose and biologically
effective dose, as well as the tolerance dose of the spinal cord and its associated
vasculature, roots, and marrow. The tolerance dose for specific tissue is a function of
irradiation volume, the total dose per fraction used, and the level of risk acceptable. The
effect of irradiation depends on the proliferative power of the tissue. Hence, skin and bone
marrow are affected early, whereas brain and spinal cord are affected late. A subacute
effect is due to demyelination secondary to injury to the oligodendrocytes and the vascular
tree. For example, the traditional fractionated dose for cord necrosis is 1.8-2.0 cGy/d.
The efficacy of dose fractionation is derived from biologic reasoning, as follows:

Repair of sublethal damage: The biologically effective dose is the probability of cell
survival after single doses of ionizing radiation. It is a function of the absorbed dose
measured in grays and based on the simple fact that irradiation causes double-stranded
DNA to break. However, the dose for a single particle to cause a double-strand break is low,
whereas that for a single-strand break is high. Yet two single-strand breaks occurring
closely in space and time may result in double-strand disruption with lethality similar to that
of double-strand break and therefore deemed irreparable.
Reoxygenation of hypoxic cells: Reoxygenation is important because tumor has
hypoxic cells, and the fraction of hypoxic cells increase after irradiation. Oxygen is the most
powerful radiation sensitizer. Hypoxic cells are radiation resistant by as much as a factor of
Reassortment of proliferating cells in the cell cycle and repopulation: A single fraction
of irradiation eliminates a portion of cells in the G2 and M phases. However, in the next 4-6
hours the cell population resumes cycling and redistribution. The radiation sensitivity varies
over the cell cycle by as much as a factor of 3. Hence, with a standard dose is 30-60 Gy.
About 18% of patients have a risk of myelopathy.
Advancement in CT and/or MRI-based planning improves the precision of
information regarding the location of tumor and critical normal structures. The traditional
treatment plan, or radiation port, is to include 2 vertebral bodies above and 2 below the
lesion. This range is based on the fact that recurrence is most common in bodies
contiguous to the site of involvement. These advancements in image-guided target
radiotherapy led to the development of intensity-modulated radiation therapy (IMRT)
stereotactic radiosurgery.

IMRT can deliver irradiation with optimized nonuniform intensities in each radiation
field. It improves conformation to the tumor and helps spare normal tissue. The advantage
is that it can generate concave and complex dose distributions. IMRT optimizes the 3
dimensional (3D) planning system and includes reverse planning to best deliver a
modulated beam-fluence profile. It is accurate to 12-15 mm.

The use of stereotactic radiosurgery and IMRT to treat spinal metastasis has
become increasingly common.

Over last two decades, the emerging technology allows the use of a robotic linear
accelerator (LINAC) that can move freely in 3D space (CyberKnife: Accuray, Sunnyvale,
CA). This method increases the number of possible beam orientations. Real-time target
tracking allows for movement within 1 mm of spatial accuracy. In addition, this form of
irradiation therapy has the following advantages:

It is a frameless system.
It references the target to internal landmarks (eg, radiographic anatomic features, bony
landmarks, implanted fiducials).
It tracks with a real-time imaging device and dynamically aligns the target with the beams.
It aims each beam individually.
The present author favors use of this robotic technology in the treatment of spinal
metastasis. Thus, delivering a relatively high dose of radiation to a small target with rapid
dose fall-off is feasible. Highly conformal beams guided with 3D imaging are used, which
gives accuracy down to submillimeter (0.4-0.7 mm).

A study from the Radiation Therapy Oncology Group (RTOG97-14) showed that 5080% of patients have adequate pain control in 3 months with single-fraction irradiation.
About 78% patients treated with irradiation remained ambulatory, and 16% of
nonambulatory patients and 4% of patients with paralysis regained function. Among those
treated with laminectomy followed by irradiation, 83% who were ambulatory remained so,
while 29% of nonambulatory patients and 13% of patients with paralysis regained function.
In a reasonably sized study reported by Dwright et al,[3] single-session stereotactic
radiosurgery seemed to have a better pain control rate and multiple sessions of
radiosurgery seems to have a better control rate at 96% vs 70%.

Radial surgery and spinal stabilization

The Spine Oncology Study Group (SOSG) defines spine instability as the loss of
spinal integrity as a result of a neoplastic process that is associated with movement-related
pain, symptomatic or progressive deformity and/or neural compromise under physiological
loads." Surgery is indicated as a stabilization procedure and/or for tissue diagnosis. It is
also used in some cases where cord compression is eminent or has occurred. In the past,
surgery was only considered in patients with disease that progressed despite radiotherapy
and in those with tumors known to be resistant to radiotherapy. Now, some surgeons have
advocated vertebral-body resection and stabilization as a preventive measure for eminent
spinal instability and/or supplementation for radiation therapy.[4]

Axial pain secondary to mechanical instability can causes significant morbidity. In

this circumstance, spinal stabilization is the treatment of choice. With the advancement in
spinal stabilization, satisfactory neurologic improvement occurs in 48-88% of patients, with
80-100% rates of pain relief. On the contrary, radiation therapy cannot reverse compression
secondary to bone, and the therapeutic response is delayed several days, even in patients
with highly radiosensitive tumors (eg, lymphoma, neuroblastoma, seminoma, myeloma).

Radical surgery not only provides stabilization, it also confers tissue diagnosis and
reduces tumor burden. It is particularly beneficial in patients whose disease progresses
despite radiotherapy and in those with known radiotherapy-resistant tumors. Surgical
decompression and stabilization, with radiotherapy, is the most promising treatment. It
stabilizes the diseased bone and allows ambulation with pain relief. Vertebral-body
resection and anterior stabilization with methacrylate and/or hardware (eg, titanium cages)
reconstruction are commonly used. This may be supplemented with posterior short
segment instrumentation using screws and rods constructs.

In general, patients who are nonambulatory at diagnosis do poorly, as do patients in whom

more than 1 vertebra is involved. Radical resection is indicated in patients with radiationresistant tumors, spinal instability, spinal compression with bone or disk fragments,
progressive neurologic deterioration, previous radiation exposure, and uncertain diagnosis

that requires tissue diagnosis. The goal is always palliative rather than curative. The
primary aim is pain relief and improved mobility.

In brief, the author advocates radical resection in most medically fit patients with
solitary metastasis with favorable histologic findings, minimal extraspinal disease, and life
expectancy of longer than 6 months. Hence, patients with breast, thyroid, prostate, or renal
carcinoma are better candidates than those with melanoma and lung cancer. In published
series, experienced surgeons used a radical, simultaneous anterior- posterior approach
with resection of the tumor (complete spondylectomy), reconstruction, and stabilization.

Surgical Approaches
Radical spondectomy and reconstruction: This is the most aggressive approach in
the surgical armamentarium. It intends to perform an en-bloc excision of the affected
vertebral body and stabilize the spine anteriorly and posteriorly with instrumentation. (See
image below.) In the cervical spine this includes skeletonizing of the vertebral arteries.
Spinal metastasis.
Laminectomy: Laminectomy is indicated less often than the other procedures
described above because most lesions are anteriorly based, and posterior decompression
may further destabilize the spine. Laminectomy does not address the anterior and middle
columns (in the Denis 3-column model of the spine) and may further compromise spinal
stability. With laminectomy, postoperative mortality is 10-15%, and morbidity (wound) can
be as high as 35%.
Posterior decompression alone is not a good solution in most cases of spinal
metastasis; the metastasis tumors are most commonly deposited anteriorly because of the
anatomic involvement of the disease. Even when the tumor involves the posterior lateral
aspect of the spine, posterior decompression provides no additional relief or substantial
functional advantage. This approach was evaluated in 84 patients with predominantly
dorsal epidural disease. Before surgery, 80% were nonambulatory, and 56% had sphincter
dysfunction. After surgery, the overall morbidity rate was 45%, and none of the patients
regained neurologic function. The complication rate was 4.7%. However, laminectomy

supplemented with stabilization with neutralizing fixation devices, such as pedicle screws,
does offer pain relief and a degree of functional recovery in a substantial number of

Transpedicular approach: The transpedicular approach is popular when tumor

involves the dorsal aspect of the vertebral body, especially when the disease extends into
the pedicle and associated dorsal elements. Facetectomy coupled with pediculectomy
allows access into the vertebral body. Followed with instrumentation a level above and
below, this procedure provides an excellent surgical result. Some surgeons suggest that
bilateral pediculectomy allows for complete vertebrectomy (spondylectomy), and anterior
augmentation with polymethylmethacrylate (PMMA) and plating optimizes surgical goals.
However, in some studies, the overall complication rate was high as 50%.
Posterior approach: The advantages of the posterior approach is (1) it permits early
identification of the cord, (2) it can address diseased dorsal elements, (3) it allows the use
of rigid constructs or long constructs in posterior areas, and (4) it addresses imbalance of
the sagittal plane and pain due to micro instability.
Costotransversectomy and lateral extracavitary approach: These are posterior lateral
approaches that can gain access to the dorsal part of the vertebral body.
Minimally invasive endoscopic procedures: Some have recently advocated the uses







decompression, percutaneous vertebroplasty and/or kyphoplasty, minimally invasive imageguided tumoral resection and spinal reconstruction, and percutaneous approach to place
pedicle screws. These techniques have revolutionized the surgical management of spinal
metastatic disease.
Kyphoplasty: Kyphoplasty is a minimally invasive procedure that may play a pivotal
role in the treatment of spinal metastases. In a single procedure, the operator can gain
access to the vertebral body by means of the pedicles to sample or remove a reasonable
amount of tumor. An infusion of PMMA into the affected bone stabilizes and/or restores the
diseased bone. This modality can be used in patients with an unfavorable health status and
may not be suitable for other forms of open surgery. Kyphoplasty has been used as a
conjoined therapy for posterolateral stabilization surgery.

The overall outcome of surgical intervention is rather controversial. In one national

statistical study, the in-hospital mortality rate was reported as 5.6%, and the complication
rate was 21.9%.[5] Unfortunately, in this study, the authors failed to address the
complications and socioeconomic impact on patients and their families and caregivers
when patients are treated conservatively. In another multinational study, a cost-effective
analysis favored early surgical intervention.[6]

Leptomeningeal metastatic disease: Metastatic disease to the neuraxis other than
the brain parenchyma and the spinal column is uncommon. The metastatic tumors are
occasionally found to have deposited onto the meninges and the cranial nerves (CNs). This
accounts for less than 5% of metastasis tumors. Spread to the pituitary gland has been
documented, but it accounts for less than 0.5% of cases of metastatic disease in the
Metastatic plexopathy is documented in the literature. Lung carcinoma, breast
carcinoma, and non-Hodgkin lymphoma can metastasize to the brachial plexus.
In most of these cases, the tumors spread from the surrounding axillary lymph nodes to the
neuronal structures.
Clinical features are pain in the upper shoulder girdle and the medial aspect of the forearm.
The lower plexus is most commonly involved; this involvement may be associated
with Horner syndrome.
Direct infiltration is by far the most common cause of neoplastic plexopathy. The
other common presentation is Pancoast tumor, in which tumor invades the nerve roots as
they exit the paravertebral space close to the apex of the lung.
Peripheral neuropathy secondary to metastatic disease is unusual; it most probably
is related to paraneoplastic syndromes. Isolated cranial neuropathy is uncommon. In most
cases, such neuropathies are associated with carcinomatous meningitis.
Carcinomatous meningitis is found in 8% of autopsies in patients with systemic
carcinoma. The most common cancers involved in carcinomatous meningitis are those of
the breast, lung, and GI, followed by melanoma, non-Hodgkin lymphoma, and leukemia.

About 48% of cancers manifest as carcinomatous meningitis.

On clinical evaluation, carcinomatous meningitis affects several levels of the
neuraxis. It has a predilection for the CNs, particularly affecting CNs VII, III, V, and VI.
The most common symptoms are headache, mental status changes, seizures, ataxia,
nonobstructive hydrocephalus, and painful radiculopathy.
The workup, including MRI, usually but not always demonstrates meningeal
enhancement at the basal cisterns. The ventricular lining is often involved. CSF analysis
requires 10 mL of CSF. The yield of abnormal cells is 45%, rising to 85% with repeat lumbar
puncture. The glucose level is low, with a high protein level. Carcinoembryonic antigen is
reported with meningeal spread of lung (89%) or breast (67%) carcinomas.
If untreated, the median survival is less than 2 months. With radiotherapy and
chemotherapy, the median survival is 5-8 months.
Chemotherapy is primarily given intrathecally, usually delivered by using an Ommaya
reservoir. A commonly used drug is methotrexate 12 mg twice weekly with oral leucovorin
rescue therapy and cytarabine and thiotepa, 50 mg and 10 mg twice weekly. Monoclonal
antibodies, lymphokine-activated killer cells, and oral etoposide were recently tried.

The outcome of metastatic disease to the spine and associated structures is uniformly
The ultimate goals are to maintain the patient's independence and dignity and to optimize
his or her comfort level.
Surgical intervention with extensive reconstruction should be performed only after thorough
evaluation of the extent of the systemic disease and only with a clear understanding of the
realistic expectation of the patients and their caretakers.