Evaluation and Management of Spinal Metastases

Michael J. Vives, MD, FAAOS

John I. Shin, MD

Dr. Vives or an immediate family member has stock or stock options held in AccelaloxNOC2 Healthcare and CreOsso and serves as a board member, owner, officer, or committee member of North American Spine Society. Neither Dr. Shin nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this chapter.

ABSTRACT

Advances in cancer treatment continually improve overall survival in multiple cancer subtypes. As a result, the number of patients who experience metastatic spine disease will increase and these individuals will live longer with their condition. Improvements in systemic treatments, radiation therapy, surgical techniques, and pain management have improved care, and at the same time, have made treatment paradigms more complex. Contemporary treatment of the patient with metastatic spine disease therefore requires a coordinated multidisciplinary team of specialists. Standardized methods for evaluating spinal instability, neurologic compression, and patient outcomes may facilitate communication and collaboration between specialists during the care of cancer patients.

INTRODUCTION

Spinal metastasis and related symptoms will eventually develop in approximately 40% of all patients with cancer. The skeletal system is the most common site of metastases. Clinically significant epidural compression requiring treatment develops only in approximately 20% of patients with metastatic disease spreading to the spine and approximately 10% of all patients with cancer. Continuous advancements in systemic treatments, radiation therapy, and surgical technique both improve care and make treatment decisions more complex. It is thus critical to identify spinal metastases early and implement a multidisciplinary approach to treatment.

PATHOGENESIS

After the liver and the lung, the skeletal system is the most common site of metastases, and the spine is the most common site of bony metastases.¹ At the time of death, as many as 80% of patients with cancer have evidence of spinal metastases as verified by postmortem examination;² however, only approximately one-half of these patients had symptoms related to the spinal spread of their cancer. Tumor cells are thought to spread to the spine hematogenously. Unlike the appendicular skeleton, the vertebral bodies contain active red bone marrow throughout the life. This highly vascular sinusoidal system makes the spine vulnerable to cancer cells.¹ Approximately 20,000 patients have metastatic epidural compression each year, and a larger number of patients require treatment of pain, fracture, or instability caused by spinal metastases.³^,⁴ Several anatomic models exist for the metastatic spread of tumor cells. A valveless extradural venous plexus could account for the high rate of lumbar metastases in prostate cancer and the prevalence of thoracic metastases in breast cancer.⁵ Another model of arterial spread of spinal metastases exists for lung cancer, in which the cancer cells are passed from the pulmonary vein to the left side of the heart and transmitted through the segmental arteries into the spine.⁶ It is thus critical to identify spinal metastases early and institute
a multidisciplinary approach to maintain or restore the patient’s neurologic function and quality of life.⁷

CLINICAL EVALUATION

The presentation of spinal metastatic disease ranges from an incidental asymptomatic finding to progressive neurologic deficit and paralysis. By far, the most common initial symptom is axial pain, which develops in 90% of patients with spinal metastases.⁸ The pain is constant, but usually worse at night and generally has no associated antecedent trauma.

Patients with metastatic spinal disease frequently have subtle signs of neurologic impairment, but these signs rarely precede axial pain. Neurologic signs and symptoms vary based on tumor location and characteristic traits. Eccentrically located tumors can often result in radiculopathy, and centrally positioned tumors with epidural compression can produce myelopathy or cauda equina symptoms. The presence of radiculopathy can assist the clinician in determining the vertebral levels involved. Usually, the radiculopathy is present for weeks or longer before the development of long-tract signs that suggest spinal cord compression. Bowel and bladder involvement is a rare and late phenomenon that usually appears in patients with profound neurologic dysfunction.¹^,⁹ Rapidly progressive neurologic deterioration (1 to 7 days) portends a worse prognosis compared with a slow course of neurologic loss (7 to 14 days).¹^,¹⁰^,¹¹ A high index of suspicion and a thorough history and evaluation are imperative when the clinician evaluates a patient with risk factors for metastatic spinal disease. Neurologic status can be objectively characterized and followed using the American Spinal Injury Association scale, which has largely replaced the Frankel scale.

Diagnostic Strategy

Although metastatic tumors account for approximately 95% of all spinal lesions, it is imperative to differentiate them from the rare primary spinal lesion.¹² A thorough patient evaluation including history, physical examination, and imaging studies often must be supplemented with a biopsy to confirm the diagnosis of primary or metastatic disease and to delineate the specific tumor type.

A patient with established metastatic disease and spinal lesions typical for the disease process can usually forgo a biopsy, although this should be carefully discussed with the patient and the oncology care team. In patients without an earlier diagnosis of cancer, spinal metastases should be strongly considered because vertebral disease is the initial manifestation of malignancy in 20% of patients with spinal lesions.¹³ Lung, prostate, breast, urologic, and gastrointestinal tract cancers are the most common pathologies that appear in such a manner.¹⁴ These patients should undergo standard staging workup including laboratory evaluation; oncologic staging studies including CT of the chest, abdomen, and pelvis, and whole-body technetium Tc-99m bone scanning; alternatively, positron emission tomography can be performed. A biopsy is performed to obtain a histologic diagnosis. Staging studies can guide the site of the biopsy; the spinal lesion(s) or other appendicular lesion(s), including long bone lesions, may be technically easier and safer to obtain the biopsy specimen from compared with some spinal lesions. Image-guided biopsy has become the first-line approach for obtaining tissue from a lesion in the spine.¹⁵^,¹⁶ Treatment should not be initiated before confirmation of the source of the lesion.

Patient Assessment and Imaging

A detailed history with a complete review of systems and family history of cancer should be the starting point of the evaluation. Inquiry should be made about routine age-appropriate screening studies for cancer, such as colonoscopy and mammography. The patient’s history of tobacco use or occupational exposure to carcinogens should be assessed. A thorough examination of the spine should be performed, with an examination of potential primary tumor sites such as the thyroid gland, breast, prostate gland, and abdomen, if metastatic disease is suspected.

Upright biplanar plain radiographs are initially obtained. Radiographs can help delineate spinal alignment, stability, pathologic fractures, and pathologic lesions. However, radiographs are not sufficiently sensitive for the reliable detection of early or small lesions. Lesions typically become visible on plain radiographs when 30% to 50% of the trabecular bone has been destroyed. Cortical destruction of the pedicle, commonly known as the winking owl sign, is highly indicative of a tumor, but most radiographic findings are nonspecific for diagnosing tumor type.

CT is often obtained to define the bony anatomy and extent of destruction. Axial imaging combined with sagittal and coronal reconstruction can assist in defining any potential instability. CT lacks the sensitivity to be used as the primary imaging modality for the detection of metastatic spinal disease. CT was found to have sensitivity of 66% and diagnostic accuracy of 89% in detecting osseous spinal metastases.¹⁷ Nonetheless, CT is invaluable in revealing skeletal detail, assessing stability, and planning surgery, and it is essential if the patient is unable to undergo MRI.

MRI provides the greatest soft-tissue detail, including epidural extension of the disease. MRI is the most sensitive (98.5%) and most specific (98.9%) imaging study for detecting spinal metastases.¹⁷ MRI of the entire spine should be strongly considered because almost 15% of
patients have clinically significant lesions at noncontiguous sites.¹⁸ Tumors usually show hypointense signal on T1-weighted images and a hyperintense signal on T2-weighted sequences. Contrast enhancement with gadolinium does not help define intraosseous tumors but can be useful in evaluating epidural disease and the soft tissue surrounding the tumor.

TREATMENT DECISION MAKING

The management of metastatic disease of the spine continues to evolve. During the late decades of the 20th century, radiation therapy was the mainstay of treatment of patients with metastatic spinal lesions, including those with spinal cord compression. Comparative studies of surgical treatment and radiation found no advantage of surgical intervention. The standard surgical strategy involved posterior decompression of the neurologic elements by laminectomy, and stabilization with rigid instrumented constructs was infrequently used. These procedures provided poor decompression because most patients had significant vertebral body involvement and associated ventral compression of the neurologic elements. In the kyphotic thoracic spine, these factors limited the amount of indirect decompression achieved by a laminectomy, and the destabilizing nature of this method led to progressive postoperative deformity.

A focus on the need to treat the anterior pathology directly through an anterior or posterolateral approach, combined with the use of rigid instrumentation, has resulted in improved benefit after surgical management of spinal cord compression from metastatic disease. The field of radiation oncology also has advanced during the past 2 decades. High-precision targeting has led to improved treatment efficacy for lesions deemed radioresistant by conventional methods. Because of these advances, several factors must be considered to determine the individualized treatment plan for a patient with metastatic spinal lesions. Larger operations may better serve long-term outcomes but are more likely to be associated with complications that could negate any potential benefit. To select appropriate interventions, it would be useful to estimate both whether a patient could tolerate surgery and live long enough to justify the risks of surgery.

Although life expectancy plays a major role in the selection of a treatment strategy, the prediction of longevity for an individual patient remains imprecise and subject to error.¹⁹ A multicenter study evaluated multiple methods to estimate patient survival. All were found to have limited predictive value; scoring systems of Bollen and Tomita were found to be the most effective.²⁰ However, the advancements in systemic therapy over the past decade has substantially improved overall survival rates for certain cancers, so continued collaboration with medical oncologists in both the academic and clinical setting will always be needed to estimate survival for an individual patient. A 2022 study reported that for patients with metastatic melanoma treated with immune checkpoint inhibition therapy, the overall survival rate was 49% at 6.5 years.²¹ In a 2020 study, patients with anaplastic lymphoma kinase-translocated non-small-cell lung cancer who were treated with anaplastic lymphoma kinase inhibitors showed overall survival rate of 63% at 5 years.²² Patients with non-driver-mutated non-small-cell lung cancer treated with immune checkpoint inhibition with or without chemotherapy showed an overall survival rate of 23% at 5 years.²³

A patient whose life expectancy exceeds 3 to 4 months may be a candidate for aggressive surgical intervention in the presence of appropriate indications. For radiation therapy, the advances in systemic treatment and resultant overall survival rates have shifted the goals of radiation therapy from palliation to more durable symptom management. To optimize patient outcomes, the complex decision process requires input from a multidisciplinary team of medical oncologists, spine surgeons, radiation oncologists, interventional radiologists, pain management, and physiatrists.

RADIATION THERAPY

Conventional Radiation Therapy

Historically, conventional external beam radiation therapy was widely considered to be the mainstay treatment for metastatic disease of the spine. The current application of this modality is best assessed separately for two distinct groups of patients: those with spinal pain caused by metastatic disease in the absence of compression of the neurologic elements and those with neurologic deficit caused by compression of the spinal cord or nerve roots. Most patients with symptomatic spinal metastases without neurologic involvement are treated palliatively with conventional radiation. It is unclear whether any specific total dosage and fractionation schedule provides superior pain relief. The most common dosage is 30 to 35 Gy delivered in 5- to 10-Gy fractions. Patients with mechanical instability from a pathologic fracture may not be palliated.

For patients with spinal cord compression from epidural extension of tumor, the efficacy of conventional radiation therapy depends on several factors. Pretreatment neurologic status and favorable tumor histology (radiosensitivity) are the most important predictors of success. Patients with spinal cord compression but no neurologic deficit have an excellent chance of maintaining ambulatory ability. A meta-analysis of several studies found that fewer than 50% of patients with neurologic deficits will recover significant function.²⁴
The most important investigation on this subject was a multicenter level I study published in 2005, in which patients with metastatic spinal cord compression were treated with surgery followed by radiation therapy or with radiation therapy alone.²⁵ With the ability to walk as the primary end point, 84% of the surgically treated patients and 57% of those treated with radiation alone had favorable outcomes. In addition to radiosensitivity of the tumor, it is also important to determine whether neurologic compression is the result of retropulsed bone from pathologic fracture and instability. In such patients, surgery as the initial intervention, followed by postoperative radiation, has a significantly better outcome than the same treatment in reversed sequence.

Stereotactic Body Radiation Therapy

Radioresistant tumors do not reliably respond to conventional radiation therapy. Conventional external beam radiation includes the tumor within a large field of normal tissue; in contrast, stereotactic delivery techniques allow high-precision targeting of tumors. In stereotactic body radiation therapy (SBRT), high-dosage radiation is delivered to a small target area with greater than 1-mm accuracy, which is accomplished using multiple beam positions (50 to 200) delivered in hypofractionated (1 to 3 sessions) doses. Because of its precise, high-dosage delivery, SBRT has better effectiveness against radioresistant tumors than conventional external beam radiation therapy.

Studies of this technique applied to spinal metastases from renal cell carcinoma, which are notably resistant to conventional radiation therapy, have found significant improvement in pain relief and local tumor control.²⁶ Additional research is necessary to define the exact role of stereotactic radiosurgery in the treatment of such patients. A systematic review compared the available data on the treatment of solitary vertebral renal metastases by en bloc resection or SBRT.²⁷ Given that the ability of either local treatment to effect a cure in such patients is unpredictable, the review conclusion was based on local tumor control. A weak recommendation was given based on the limited available evidence for considering SBRT as a first-line treatment because it is less invasive than conventional radiation therapy and offers similar local control rates as en bloc resection.

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