CANCER DIAGNOSIS AND MANAGEMENT

HAMED A. DAW, MD Department of Hematology and Oncology, Cleveland Clinic

MAURIE MARKMAN, MD Director, Taussig Cancer Center; chairman, Department of Hematology and Oncology, Cleveland Clinic; and associate editor, Cleveland Clinic Journal of Medicine

Epidural spinal cord compression in cancer patients: Diagnosis and management

ABSTRACT In most patients with spinal cord compression due to epidural metastasis, the initial symptom is progressive back pain with an axial or radicular distribution, but early symptoms are often nonspecific. Since the key prognostic factor is the neurologic status at the time of presentation, and since early complaints are often nonspecific, a high index of suspicion is needed to diagnose this complication early.

KEY POINTS With prompt management, ambulatory status can be maintained in about 80% of patients, but delays result in a rapid loss of function.

Back pain tends to be localized initially and may increase with lying supine, coughing, sneezing, flexing of the neck, and moving.

Differentiating back pain of epidural spinal cord compression from that of degenerative joint disease is critical. Pain of degenerative joint disease almost always affects the low cervical or low lumbar spine, whereas pain of metastatic compression occurs at any level. Lying down improves the pain of degenerative disease but typically worsens pain due to metastatic compression.

Magnetic resonance imaging is the diagnostic test of choice for epidural spinal cord compression.

Steroids should be given to all patients suspected of having spinal cord compression.

P I N A L C O R D C O M P R E S S I O N due to epidur-al metastasis needs to be recognized

early and treated promptly, since any delay may doom the patient to a very uncomfortable demise, with pain, immobility, and inconti-nence . W i t h prompt treatment, 8 0 % of patients maintain their ability to walk. In most patients, the initial symptom is progressive back pain with an axial or radicular distribu-tion, but early symptoms are often nonspecif-ic. Therefore, a high index of suspicion is needed to diagnose this complication early.

• PATHOPHYSIOLOGY

In cancer patients, epidural spinal cord com-pression is usually the result of hematogenous spread of primary tumor cells to the bone mar-row of the vertebral column, where metastatic tumors grow. In time these tumors can cause cord compression, either by extending into the epidural space or by causing vertebral body collapse.1 In addition, animal studies have demonstrated that blood flow abnormalities such as vascular congestion, edema, and hem-orrhage of the spinal cord at the level of the compression also play a role. These findings could be caused either by occlusion of venous outflow from the cord,2 or by occlusion of the central perforating vessels of the spinal cord.3

Animal studies have also demonstrated that neurologic deficits are more likely to reverse when compression is gradual rather than acute.4

Vasogenic cord edema has been correlated with increased synthesis of prostaglandin E2, which can be inhibited by steroidal and non-

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SPINAL CORD COMPRESSION DAW AND M A R K M A N

steroidal anti-inflammatory drugs, as well as by serotonin antagonists (eg, cyproheptadine).5

These findings may lead to new types of ther-apy for this condition.

• CLINICAL PRESENTATION

Back pain Back pain is the most common presenting symptom, occurring in 9 5 % of patients with epidural spinal cord compression. It may pre-cede neurologic symptoms by weeks or months.

Caused by expanding metastases stretch-ing the periosteum, the pain: • C a n be either localized or referred,

although it is usually localized initially • May increase with lying supine, coughing,

sneezing, flexing the neck, moving • May be described as a deep, dull ache • May awaken the patient from sleep • May not respond to analgesics • May include tenderness on percussion

over the involved area • May be radicular, occurring near the area

of compression in a dermatomal pat tern— unilaterally when the cervical or lumbar spine is involved, and bilaterally when the thoracic spine is involved.6

Spinal cord compression vs degenerat ive joint disease Differentiating the pain of metastatic epidural spinal cord compression from the pain of degenerative joint disease is critical. Clinical clues include: • Location of the pain: pain of degenerative joint disease almost always affects the low cer-vical or low lumbar spine, whereas pain of metastatic compression occurs at any level • Positional relief: lying down improves the pain of degenerative disease but typically worsens pain due to metastatic compression.

Neurologic signs Neurologic signs or symptoms in patients with metastatic epidural spinal cord compression usually indicate disease progression.

Motor weakness usually follows the development of pain by weeks or months. It affects proximal muscles, creating difficulty when climbing stairs or rising from a chair.

W h e n weakness is present, hyperreflexia and an extensor plantar response confirm involve-ment of the corticospinal tracts.

Sensory loss may occur below the level of cord compression and corresponds to a skin dermatome. Loss of proprioception is common when the posterior spine is involved.

Signs and symptoms of autonomic dys-function such as hesitancy, urinary retention, and urinary and fecal incontinence occur late and are particularly ominous. Although nar-cotic analgesics can cause urinary retention, spinal cord compression should be ruled out first in any patient at risk.

• PROGNOSIS

T h e prognosis depends very much on the patient's neurologic status at the time of diag-nosis.7 Indicators of poor prognosis include:

Impaired ambulation is the most reliable indicator. If ambulatory at the initiation of therapy, 8 0 % of patients remain able to walk after treatment. Only 3 0 % to 4 0 % of patients with motor dysfunction before treatment are able to walk after treatment.

Rapid symptom onset. Animal studies show that neurologic deficits are more likely to reverse when compression is gradual rather than acute.4

Duration of motor dysfunction greater than 4 8 hours indicates that the underlying injury has become irreversible.

Poor sphincter control at presentation indicates that epidural spinal cord compres-sion is in the later stages, when treatment has little or no effect.

• IMAGING STUDIES

Cancer patients in whom metastatic epidural spinal cord compression is suspected should undergo an immediate, careful, detailed neu-rologic examination, including imaging stud-ies. T h e following imaging studies help to con-firm the diagnosis.

Plain radiography Plain radiography detects bony abnormalities (eg, absence of a pedicle, lucencies in the ver-tebral body) in 7 0 % of patients with epidural spinal cord compression.8 However, more

Delays in diagnosis and treatment result in rapid decline

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SPINAL CORD COMPRESSION DAW AND MARKMAN

T A B L E 1

Current management of metastatic epidural spinal cord compression Radiotherapy is the treatment of choice for most patients: 30 Gy delivered in 10 fractions over a period of 2.5 weeks Surgery is appropriate if the patient has:

Spinal instability Unknown diagnosis No response to radiotherapy Already received the maximum tolerable dose of radiation therapy to the area Intractable pain despite radiotherapy and large doses of corticosteroids

than 5 0 % of the bone mass must be lost before any radiographic abnormality can be detected. Plain radiography is less useful in patients with epidural spinal cord compression due to lymphoma or pediatric malignancies. In these patients, a paraspinal soft-tissue mass is usual-ly the cause.

Magnetic resonance imaging Magnetic resonance imaging (MRI) is the imaging study of choice for diagnosing epidur-al spinal cord compression. It is noninvasive, easily detects paraspinal soft-tissue masses, detects additional sites of vertebral involve-ment (multiple sites of compression can be detected in 9 % to 3 0 % of patients),9 and is as accurate as myelography or computed tomog-raphy.10 T h e addition erf gadolinium contrast offers better detection of epidural, intradural extramedullary, intramedullary, and lep-tomeningeal lesions.

Computed tomographic myelography Before the advent of MRI, computed tomog-raphy—performed after injecting metriza-mide - was the tool of choice for diagnosing metastatic epidural spinal cord compression. This procedure is currently indicated in the following specific clinical situations: • If MRI is not available • If the patient has a pacemaker • If the patient is too large to fit in the MRI

machine • If the patient has severe claustrophobia, is

unable to lie flat for the duration of the

Autonomic dysfunction has a poor prognosis

test, or has uncontrolled pain. In a patient with complete myelography

block, contrast can be administered from above through a C I - 2 puncture to demarcate the upper border of the block and to look for other epidural lesions.

Adverse effects associated with this proce-dure include infection, bleeding, and a 10% to 2 0 % risk of iatrogenic neurologic deteriora-tion attributed to the lumbar puncture in patients with complete subarachnoid block.?

• MANAGEMENT: RELIEVING PAIN AND PRESERVING FUNCTION

Treatment of metastatic epidural spinal cord compression (TABLE 1) should focus on relieving pain and preserving neurologic function. Achieving these two goals will not only pre-serve the patient's quality of life, but also reduce the burden on the caregiver, since patients who progress to paraplegia require extensive and costly care.

Corticosteroids Corticosteroid therapy is generally started as soon as the diagnosis of spinal cord compres-sion is entertained. T h e goals of corticosteroid therapy are to reduce the vasogenic edema caused by the expanding cancer, to control pain, and to maintain neurologic function.

Exact dosages, schedules, and duration of therapy have not been established. A loading dose of dexamethasone 10 to 100 mg intra-venously followed by 4 to 24 mg orally or intra-venously every 6 hours has been suggested. Animal models point to a dose-dependent response following corticosteroid administra-tion. In these models, the improvement in neu-rologic function peaked at day 2 of corticos-teroid therapy and had diminished by day 4-3

Corticosteroid therapy is usually contin-ued throughout radiation therapy and is tapered slowly toward the end of treatment. During the tapering period, patients should be carefully followed, and any neurologic deteri-oration should prompt an increase in the steroid dosage.

High-dose dexamethasone. Some experts have hoped that high-dose corticosteroid therapy would be more efficacious than con-ventional regimens. But three prospective,

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randomized trials11"13 of high-dose dexam-ethasone therapy showed varying results: • Greenberg et al11 found that high-dose dexamethasone (a 100-mg intravenous bolus, followed by 96 mg/day orally for the first 3 days, then tapered) brought substantial pain relief in patients undergoing radiation therapy, but had no effect on motor ability. • S0renson et al12 found that patients who received high-dose dexamethasone (a 96-mg intravenous bolus, followed by 96 mg orally for 3 days, then tapered) in conjunction with radiation therapy maintained gait function longer than patients who received no dexam-ethasone with radiation therapy. • Vecht et a P found no advantage of high-dose dexamethasone therapy vs conventional doses in terms of either pain relief or neuro-logic function.

High-dose regimens carry a risk of serious toxicity; the incidence of serious toxic effects was 14% in one study.14 This risk must be weighed agains: the anticipated benefits.

Radiation therapy Radiation therapy is the treatment of choice for most patients with epidural spinal cord compression. A common schedule is a dose of 30 Gy delivered in 10 fractions over 2.5 weeks. T h e treatment field includes the area of spinal cord compression, with a margin of two verte-bral bodies above and below the area involved with disease. Patients with prostate or breast cancer often present with multiple areas of involvement.

Response to radiation therapy is evaluated in terms of pain relief and stabilization or reversal of neurologic deficit. Tumors classified as "radiosensitive" (eg, lymphoma, seminoma) respond better than "radioresistant" tumors (eg, sarcoma, melanoma), with a complete response rate of 7 7 % vs 30%. 1 5 Predictors of more favorable response include favorable his-tology (prostate or breast cancer, myeloma), earlier diagnosis, and less neurologic deficit at presentation.16

Surgery Although radiation therapy is the treatment of choice for most patients with epidural spinal cord compression, surgery is also useful in selected patients. Indications include the

need to establish a diagnosis in patients with no known cancer, to treat spinal instability, to treat pathological fractures caused by sympto-matic spinal metastases, and failure to respond to radiation therapy. On the other hand, recovery from spinal surgery is not devoid of complications, and this potential morbidity should be taken into account when surgery is considered for patients with poor life expectancy and several sites of metastatic dis-ease.

Anterior decompression with mechanical stabilization is the surgical technique of choice for epidural metastases arising from the vertebral body. Several retrospective studies17

and a small prospective study18 failed to show any advantage of laminectomy when com-pared with radiotherapy alone.

Chemotherapy Chemotherapy has only a limited role in the management of epidural spinal cord compres-sion. It may be used in adults who have a chemosensitive tumor (eg, germ cell tumor, Hodgkin disease) and who cannot undergo surgery or radiation therapy, or as adjuvant therapy after surgery or radiotherapy.

In children with chemosensitive tumors (eg, neuroblastoma, Ewing tumor), chemo-therapy should be considered because of the risk of radiation-induced growth abnormalities or secondary tumors. Chemotherapy should also be considered in cases of recurrent spinal cord compression by a chemosensitive tumor in a site of previous radiation or surgery.

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Trials of high-dose corticosteroids showed varying results

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ADDRESS: Ha med A. Daw, MD, Department of Hematology and Oncology, T40, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail dawh@ccf.org.

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