Summary of Key Points
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A growing number of patients with spinal metastasis are living longer due to better systemic therapies.
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The management of patients with spinal metastasis requires a multidisciplinary approach.
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Primary care physicians should maintain a high level of suspicion for back pain in patients with cancer.
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The use of multimodal imaging studies is mandatory for evaluation of spinal tumors and surgical planning.
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Preoperative embolization may decrease the rate of intraoperative complications, especially in highly vascular tumors.
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Surgical indication in spinal metastasis depends highly on prognostic factors and overall survival. Surgery will delay chemotherapy and radiation and should only be considered after applying standard prognostic tools and spinal instability scores.
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Surgery usually focuses on prolonging ambulatory and survival status in patients with spinal metastasis, and it can be curative in the case of single metastatic lesions.
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Surgery followed by radiation therapy is the most appropriate therapeutic strategy in metastatic spinal cord compression in patients with an expected overall survival of more than 3 months.
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Surgical outcome studies demonstrated that patients treated surgically did better than those treated with radiation alone in terms of maintaining or regaining their ambulatory status, achieving better pain control, and keeping urinary sphincter control for a longer period.
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Vertebroplasty and kyphoplasty are important tools in the management of mechanical pain in the setting of pathologic compression fractures.
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Few guidelines are available for the treatment of spinal metastasis, and most of them are based on expert opinions instead of high-quality clinical evidence.
Epidemiology
In the United States each year 1.4 million new diagnoses of cancer are performed. The skeleton is the third most common place for metastasis after liver and lungs, respectively. Studies estimate that almost 70% of patients with the most prevalent primary cancers—namely lung, prostate, and breast—will develop bony metastasis.
The spine is the skeleton structure most frequently affected by cancer. The peak incidence of spinal metastases happens between 40 to 65 years of age, which is also the period of highest risk for cancer. Nevertheless, only 5% to 10% of the spinal metastasis will present with symptoms related to epidural disease. It is expected that in the next years more patients with spinal metastasis will be living for a prolonged period of time mainly due to the advancements in multimodal therapy, including oncologic spine surgery, radiation oncology, and enhanced systemic therapies.
Classification of Spine Tumors
Spinal tumors can be divided according to their anatomic location in intramedullary, intradural-extramedullary, and extradurally. As the majority of spinal metastasis are extradural, this will be the focus of the following discussion. The thoracic spine is the most common spinal segment affected by metastatic tumors, representing approximately 70% of cases, followed by the lumbar spine with 20%, with the remaining 10% being divided between the cervical spine and sacrum. Regarding the specific location of the extradural compartment, metastatic lesions can be further divided into those affecting the vertebral body (with or without posterior bony structure involvement), the paravertebral region, and the epidural space ( Fig. 115-1 ).
Clinical Presentation
Metastatic spinal lesions might cause a wide variety of symptoms, especially pain (both from oncologic and mechanical reasons related to spinal instability), sensory symptoms, motor impairment, or, more rarely, autonomic dysfunction. The variability in symptoms from patient to patient is mainly related to the tumor growth rate (which is directly related to the likelihood of developing myelopathy), the degree of bone involvement leading to fractures, the severity of spinal cord and nerve root compression, the stage of systemic disease, and the intrinsic histologic characteristics of each tumor.
Pain
Pain is by far the most common presenting symptom in patients with spinal metastasis, occurring in 85% to 95% of patients. It is crucial that general practitioners and primary care physicians are able to promptly recognize the importance of pain as a red flag that warrants an immediate imaging workup in patients with known primary cancer, because pain usually precedes the development of neurologic symptoms by several weeks or even months. In fact, it has been demonstrated that early diagnosis of metastatic spinal disease may be one of the most important factors affecting the patient’s long-term neurologic and oncologic prognosis.
There are essentially three types of pain that affect patients with spinal metastasis: local pain, mechanical pain, and radicular pain. Local pain is caused by tumor growth (usually referred to as oncologic pain) and is believed to result from periosteal stretching as well as tumor-induced inflammation. Patients usually describe this pain as aching, deep, and commonly occurring during the night and improving with activity. On physical examination it might be elicited by palpation over the posterior spinal elements. This type of pain is usually responsive to anti-inflammatories and corticosteroids. It may also be responsive to radiotherapy.
The second type of pain is mechanical. This pain is variable with position and movement and is characteristically unresponsive to nonsteroidal inflammatory drugs (NSAIDs) and corticosteroids in contrast with oncologic pain. Mechanical back pain usually occurs with or precedes spinal instability caused by compression fractures in the vertebral bodies or fracture of the posterior spinal elements. Mechanical back pain is responsive to external stabilization (brace) or surgical stabilization of the spine.
Lastly, radicular pain is caused by direct tumor compression of the emerging nerve roots or narrowing of the neural foramina due to pathologic fractures leading to nerve root impingement. Patients complain of a sharp, shooting pain radiating in a dermatome pattern.
Motor/Autonomic Dysfunction
Neurologic status at the time of diagnosis is one of the most important prognostic factors for long-term neurologic outcomes in patients with metastatic epidural spinal cord compression (MESCC). Motor dysfunction is the second most common symptom in patients with MESCC after pain. Myelopathy, radiculopathy, or both may cause muscle weakness. In patients with MESCC, the incidence of at least some degree of muscle weakness varies from 60% to 85%.
Although prominent autonomic complaints are much more rare than motor dysfunction, patients with MESCC and motor compromise frequently present with at least some degree of autonomic dysfunction involving bladder, bowel, and sexual complaints. Additionally, sensory symptoms in a saddle pattern such as anesthesia, hypo- or hyperesthesia, and paresthesia typically happen in parallel with motor dysfunction. It is important to note for management purposes that patients who present with motor dysfunction will likely progress to complete paralysis in the absence of treatment, and in such cases, intervention should be performed as early as possible to avoid such outcome.
Diagnostic Imaging
Plain Radiographs
Plain radiographs are a common screening modality for patients with spinal disorders because they are easily available and cheap. Nonetheless they have a limited role in the diagnosis of MESCC. In fact, it has been demonstrated that at least 50% of the vertebral body must be compromised by an osteolytic lesion (the most common type of metastatic tumor) before the abnormality can be identified on plain x-ray films. Although of limited use, in advanced metastatic spinal disease, radiographs may provide some evidence of compression fractures, spinal deformity, and paraspinal masses.
Bone Scan
Bone scanning is a nuclear imaging method that is frequently used as a screening tool for identifying metastatic bony disease in patients with cancer. A bone scan is capable of revealing metastatic lesions in an earlier stage when compared to plain radiographs. By demonstrated increased uptake of the intravenously injected radiotracer, bone scan images correlate with increased metabolic activity in the skeletal system. Nevertheless bone scans have low specificity for cancer, and increased metabolic activity due to inflammation or infection must be taken into account as possible differential diagnoses. Also, the degree of detail in bone scans is very low, and for purposes of diagnosis exclusion or surgical planning, correlation with computed tomography (CT) or magnetic resonance imaging (MRI) is mandatory. Today, in most reference oncologic centers, positron emission tomography (PET) scan with 18 F-fluorodeoxyglucose (FDG) has replaced bone scan for purposes of whole-body screening for metastases.
Computed Tomography
Computed tomography provides the ideal imaging of bone and is useful for differentiating between osteolytic and osteoblastic (sclerotic) lesions as well as for identifying the presence of pathologic fractures ( Fig. 115-2 ). CT is extremely important for surgical planning because it provides a deeper insight into the underlying bone anatomy that will guide the planning of the spinal instrumentation to be performed for each patient. Although CT provides more than 90% sensitivity and specificity for bone structures, it offers limited visualization of the surrounding soft tissue structures, with studies demonstrating that CT scan is able to properly depict epidural and soft tissue metastasis in only 50% of the cases.
Magnetic Resonance Imaging
Magnetic resonance imaging is by far the most important imaging tool in evaluating metastatic spinal tumors. It provides valuable information about several crucial aspects of spine anatomy, enabling ideal visualization of the bone marrow, surrounding paraspinal soft tissues, meninges, spinal cord, nerve roots, and intervertebral discs.
MRI protocols to evaluate spinal tumors should include T1- and T2-weighted studies with and without contrast and in axial, sagittal, and coronal cuts. Fat-supression studies might help in evaluating contrast-enhancing lesions because T1-weighted images produce a high-intensity signal which may overlap with the hypersignal from the fat from the bone marrow. According to some studies, diffusion weighted imaging could offer some help in differentiating osteoporotic and pathologic fractures, although this sequence is not routinely included in standard protocols for the evaluation of metastatic spinal lesions in most reference centers.
Angiography
Some types of tumors leading to spinal metastasis are highly vascularized and, as such, may impose a higher degree of surgical challenge. Additionally, several intra- and postoperative complications have been associated with increased blood loss. Renal cell carcinoma, thyroid carcinoma, hepatocellular carcinoma, and neuroendocrine tumors are well known for their high degree of vascularity and, consequently, profuse intraoperative bleeding. One of the strategies to prevent these hemorrhagic complications includes the use of preoperative angiography. Angiography not only allows a better understanding of the tumor’s vascular supply but also, and most important, may enable preoperative tumor embolization, with significant potential of decreasing the amount of intraoperative blood loss.
Management
The management of a patient with a metastatic spinal tumor is optimally performed utilizing an interdisciplinary approach. Variables such as status of the primary disease, comorbidities, functional status, age, and life expectancy must be considered when selecting the most adequate therapeutic options for each patient. Moreover, the treatment of spinal metastases is mainly palliative (with rare exceptions, such as with single metastatic lesions in which an oncologic cure may be achieved), and the three fundaments of the management are pain control, maintenance of neurologic status, and preservation or restoration of spinal stability.
Treatment of Metastatic Epidural Spinal Cord Compression
Metastatic epidural spinal cord compression is defined as the presence of tumor in the spinal canal causing compression of the spinal cord. Around 5% to 10% of cancer patients will develop MESCC. MESCC is considered a surgical emergency/urgency, and surgery has been considered the mainstay of treatment along with corticosteroids and radiotherapy. Since Patchell and associates’ prospective randomized controlled trial comparing decompressive surgical resection associated with radiation therapy versus radiation therapy alone, it has been accepted that a greater improvement in neurologic function can be expected in patients in which surgery is added to radiation therapy. In this study, patients in the surgery plus radiotherapy group had a higher ambulatory status at the time of the 3-month follow-up when compared to those treated with radiotherapy alone (84% versus 57%). Furthermore, patients who were able to ambulate before treatment were more likely to maintain their ambulatory status after surgical decompression with radiation therapy (94%) than those who received radiation only (74%). Finally, a higher percentage of patients who were nonambulatory preoperatively regained their ability to walk after surgery plus radiotherapy when compared with the radiation-alone treatment group (62% versus 19%) ( Fig. 115-3 ).
Surgery also plays a crucial role in the treatment of MESCC, especially in cases involving radioresistant tumors, recurrence after radiation, spinal instability, spinal cord compression, and rapid neurologic decline. The exceptions, in which radiotherapy is still an option, are those patients with no evidence of instability and highly radiosensitive tumors (lymphoma and multiple myeloma). Additionally, patients with short expected survival times (less than 3 months) may also be candidates for radiotherapy alone.
Surgery is not always indicated in the treatment of MESCC. This is especially true in patients with a poor oncologic prognosis. Rades and colleagues developed a scoring system to evaluate which patients should not be operated. In order to build their 25-point score, the authors considered the main prognostic factors in spine oncology, namely performance status (Eastern Cooperative Oncology Group), tumor type, presence of other metastatic lesions, visceral metastasis, interval from cancer diagnosis to MESCC, ambulatory status prior to radiotherapy, and interval to the development of motor deficits. This study demonstrated that patients with a score ≥ 24 points have a very high likelihood of dying within 2 months (positive predictive value of 96%) and as such should be offered less aggressive treatment options such as single-dose radiotherapy and supportive care.
Chemotherapy/Hormonal Therapy
Long-term control of spinal metastases depends largely on the systemic chemotherapy. It should be noted, however, that chemotherapy must be suspended when surgical intervention is necessary and that, after surgical intervention, most surgeons would recommend a waiting period of at least 3 to 4 weeks before chemotherapy may be reinitiated to avoid the risk of wound breakdown. The choice of the best suitable agent is highly contingent on the histology of the tumor. The specimen for histologic analysis can be obtained through surgery or a percutaneous biopsy. Other more accessible metastatic lesions outside the spine can also be used for this purpose.
For two of the most common types of cancer leading to spinal metastases, namely prostate and breast cancer, the use of hormonal therapies are of utmost importance. Estrogen antagonists like tamoxifen and aromatase inhibitors such as letrozole are important protagonists in breast cancer. In parallel, androgen blockade with GnRH agonists is also an important tool in the management of patients with prostate cancer.
Corticosteroids
In addition to standard chemotherapy, other drugs play an important part of the medical arsenal to prevent or alleviate the symptoms in patients with spinal tumors. Corticosteroids, bisphosphonates, and analgesic agents have a key role in the management of these patients.
Corticosteroids can be used to decrease the spinal cord edema if compression occurs. Some studies suggest the use of steroids to reduce the size of metastatic lesions from hematogenous tumors. Sorensen and coworkers demonstrated a significant improvement in the ambulation status at 3 and 6 months with the use of high-dose steroids in MESCC prior to radiotherapy compared to radiotherapy alone. Unfortunately, to date no clear guidelines exist regarding the use and doses of corticosteroids in MESCC; the decision is largely dependent on the treating team and seems to mainly depend on the existence of motor deficits.
Analgesia
Poorly managed pain remains one of the most important problems affecting the quality of life of cancer patients because it contributes to depression, anxiety, and fatigue. In spite of the efforts of the American Pain Society and the World Health Organization, a large number of cancer patients still suffer from inadequate pain control.
The management of pain associated with MESCC should begin with nonopioid analgesics, mainly nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs are efficacious for bone pain such as the one consequent of periosteal stretching. However, if pain cannot be controlled with these drugs, physicians should not hesitate to use opioids. The choice between strong opioids or weaker opioids should be made individually considering the level of pain control with each medication and the side effects derived from them. Adjuvant drugs, such as corticosteroids, antidepressants, as well as gabapentin and amitriptyline in the case of neuropathic pain, may also play an important role in pain control in patients with spinal metastasis. Irrespective of the selected treatment, cancer patients should have their pain status reassessed from time to time and monitored for the side effects from pain medications.
Conventional Radiotherapy and Stereotactic Radiosurgery
Conventional radiotherapy has a well-defined and important goal in the treatment of spinal metastases. It is well-known that spinal cord cannot tolerate high doses of radiation. Therefore, the volume of spinal cord receiving a total equivalent dose of 8-Gy should be limited, as more than half of the complications related with myelopathy occur beyond this level. Consequently, the efficacy of radiation therapy might be limited by the tumor anatomic location, especially in radioresistant tumors. Fortunately, advances in radiation therapy have allowed the delivery of higher doses of radiation through the use of new techniques such as modulated radiation therapy (iMRT) and stereotactic radiosurgery (SRS), with better results in terms of local control rates, even for radioresistant tumors such as renal cell carcinoma.
In a review by Gerszten and associates, the authors found that 60% to 80% of patients were able to keep ambulatory status after conventional radiation for treatment of spinal cord compression. In the case of nonambulatory patients, according to the literature 20% to 60% may be able to regain ambulation after radiation. As previously mentioned, pain control is one of the main goals in the treatment of patients with metastatic spinal disease, and fractionated radiotherapy has been shown to be very efficient in reducing pain, with a significant decrease in pain levels in approximately 50% to 70% of treated patients.
According to the Spine Oncology Study Group (SOSG), in patients in whom no there is no biomechanical instability, no spinal cord compression, and did not received prior radiation treatment, as well as for those with known radiosensitive tumors, radiotherapy alone may be the appropriate initial therapy in order to maintain ambulation status and achieve pain control.
To date there are no available randomized studies defining the role of SRS in comparison to conventional radiotherapy. Nevertheless, lower-quality evidence demonstrates that 85% to 100% of patients report effective pain control and 57% to 92% have an improvement of their neurologic symptoms with SRS. The optimal dose is still unclear, but single fraction (16 to 24 Gy) and hypofractionated plans are commonly used. The local control rate for SRS in the literature is around 90% for most studies. Additionally, due to the intrinsic advantage of SRS regarding anatomic accuracy, in the absence of diffuse spinal disease, most centers have preferred the use of SRS over conventional radiation therapy whenever possible. As with chemotherapy, there must be an appropriate time period between surgery and SRS to allow for appropriate wound healing.
In a guideline published by the American Society of Radiation Oncology, external beam radiotherapy remains the mainstay for the treatment of painful, uncomplicated bone metastases. Several fractionation regimens have been demonstrated to offer appropriate rates of palliation including 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, and 8 Gy in a single fraction.
It has also been found that stereotactic body radiation therapy (SBRT) may also be useful for patients with newly discovered or recurrent tumors in the spinal column or paraspinal areas. However, it has been suggested that this option is indicated only for patients who fit specific inclusion/exclusion criteria and receive treatment in centers with adequate experience and training in SBRT.
Finally, published guidelines on the issue have suggested that surgical decompression and stabilization associated with postoperative radiation therapy should be offered to patients with single-level spinal cord compression or spinal instability, unless the life expectancy of these patients is too short (less than 2 to 3 months), as previously mentioned.
Spinal Instability
The spinal structure that sustains 80% of the axial load is the vertebral body. Unfortunately, this is also the most frequent site affected by spinal metastases. The bony destruction caused by the tumor growth inside the vertebral body commonly leads to instability and compression fractures. Three factors related to the vertebral body are the most important in predicting instability: the remaining tumor-free cross-sectional area of the vertebral body, tumor size, and bone mineral density. In a study by Taneichi and colleagues, in 53 patients with osteolytic metastatic lesions, the threshold for vertebral body collapse was 50% to 60% of the vertebral body compromised by tumor in the thoracic spine and 35% to 40% in the lower thoracic and lumbar spine.
Classification of Spinal Instability
Spinal instability is so crucial for the decision making in spine oncology that the Spine Oncology Study Group developed specific classification criteria for defining instability in the setting of spinal tumors. The Spine Instability Neoplastic Score (SINS) uses a comprehensive group of factors that directly influence spinal instability. SINS has been developed not only to aid spine surgeons and oncologists in developing algorithms for treatment but also help primary care physicians and radiation and medical oncologists in defining the time of referral for possible surgery.
The components of the scoring system include the global spinal location of the tumor, with tumors in mobile segments such as the cervical spine receiving a greater score than those in more stable areas such as the sacrum and the thoracic spine. Pain is also taken into account, and mechanical pain receives a greater score than local pain due to periosteal stretching. The type of lesion also affects instability, with lytic lesions being responsible for more instability. Spinal alignment with subluxation and translation also greatly contribute to the development of instability. Vertebral body collapse, especially when greater than 50%, will also have a major effect upon spinal instability. Finally, posterior involvement, particularly with bilateral involvement of pedicles, facets, and costovertebral joints, will also receive greater scores in the SINS. A study by Fourney and coworkers that evaluated the inter- and intraobserver reliability of the SINS criteria in determining potentially unstable or unstable lesions found a sensitivity of 95.7% and a specificity of 79.5%.
It should be noted, however, that in addition to the criteria evaluated with the SINS score, preoperative quality-of-life status should also affect the decision making regarding the necessity of surgery in patients with metastatic spinal disease. The Global Spine Tumor Study Group recommends the use of the Euroquol (EQ5D) assessment tool, a easily interpreted 5-point validated questionnaire, for all patients with metastatic disease ( Fig. 115-4 ). Although many studies have shown clear improvements in quality of life after surgery for spinal metastases, previous studies demonstrated that complication rates may reach up to 25% in operated patients. Ultimately, with the use of proper indication criteria, studies demonstrated that as many as 80% of operated patients report that they are satisfied or very satisfied with surgical outcomes.
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