Bone metastases are a growing problem among patients with cancer due to increasing life expectancy, with the spine being the most frequently affected site. Spinal metastases primarily arise from breast, lung, prostate, and renal cancers.553,554 Extradural lesions account for about 95% of spinal tumors, mostly in the thoracic region.
Some patients are found to have vertebral involvement as an
asymptomatic, incidental finding. However, for most affected patients, pain is the primary presenting symptom preceding neurologic dysfunction.
Three types of pain have been classically defined. Local pain due to tumor growth is often described as a constant, deep aching that improves with steroid medications. Mechanical back pain varies with movement and position and is attributed to structural spinal instability. While seldom
responsive to steroids, mechanical pain can be alleviated by surgical stabilization. Radicular pain is a sharp or stabbing sensation that occurs when nerve roots are compressed by the tumor. Patients may experience any one or a combination of these types of pain.
Spinal cord compression is the most debilitating complication of spine metastases. It affects 5% to 10% of all patients with cancer, with more than 20,000 cases diagnosed each year in the United States.555 The majority of patients initially complain of progressive radicular pain.556 This is followed by neurologic symptoms such as motor weakness and sensory loss, and may even include autonomic bladder dysfunction. If left
untreated, neurologic deficits rapidly progress to paralysis. Unfortunately, a study of 319 patients with cord compression revealed significant delay in the report of initial pain (3 months) as well as diagnosis (2 months) that can lead to irreversible spinal cord damage.557 Therefore, it is paramount that the clinician watches for early suspicious signs and establishes
prompt diagnosis by spine MRI. Once diagnosed, spinal cord compression is considered a medical emergency; intervention should be implemented immediately to prevent further neurologic decline.
Treatment Overview
Dissemination to the spinal column is largely incurable. Therefore, the goals of treatment are palliation and improvement of quality of life through preservation of neurologic function, pain relief, and stabilization of
mechanical structure. One exception is slow-growing cancers (mainly renal cell carcinoma) with solitary spinal metastasis, for which surgery may achieve possible cure.558 Patients with spine metastases require care from a multidisciplinary team, including neurosurgeons; orthopedic surgeons;
radiologists and interventional radiologists; and specialists in pain management; care of the bowel, bladder, and back; and ambulatory support.
Version 5.2020 © 2021 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-47 The type and aggressiveness of the primary tumor often dictates the
choice of treatment, as different cancers have varying sensitivities to systemic therapy and RT. In addition, patient characteristics including PS and comorbidities will determine whether they can tolerate surgery and, if so, which surgical technique should be used.
Surgery
There is general consensus that a patient should have a life expectancy of at least 3 months to be a surgical candidate. Paraplegia for over 24 hours is a strong relative contraindication due to low chances of improvement when prolonged neurologic deficits exist before surgery.559 Patients with hematologic malignancies should also be excluded, as they are best managed by RT or chemotherapy. Because estimation of life expectancy can be difficult, several groups have developed prognostic scoring systems to help predict surgical outcomes.560-563
Modern surgical techniques enable surgeons to achieve 360°
decompression of the spinal cord, and stabilization can be performed concomitantly, if required. The development of a plethora of spinal implants composed of high-quality materials such as titanium greatly improves reconstruction outcome. The surgical approach—anterior, posterior, or combined/circumferential—is primarily determined by disease anatomy.564,565
Sundaresan and colleagues558 reported favorable results using a variety of surgical approaches on 80 patients with solitary spine metastases. Both pain and mobility were improved in the majority of patients. OS reached 30 months, with 18% of patients surviving 5 years or more. The best outcome was observed in patients with kidney and breast cancers.
Surgery followed by adjuvant EBRT has emerged as a highly effective approach in relieving spinal cord compression and restoring function, especially for solid tumors. A meta-analysis including 24 surgery cohort
studies and four RT studies found that patients are twice as likely to regain ambulatory function after surgery than RT alone.566 However, data also revealed significant surgery-related mortality (6.3%) and morbidity (23%).
In another review of literature from 1964 to 2005, anterior decompression with stabilization plus RT was associated with superior outcome over RT alone or laminectomy, achieving 75% mean improvement in neurologic function. However, high surgical mortality rate (mean 10%) was also reported.567
To date, only one relevant randomized trial has been reported.568 Approximately 100 patients with metastatic spinal compression were randomized to surgery plus postoperative RT or RT alone. Compared to the RT group, significantly more patients in the surgery group regained walking ability (84% vs. 57%; P = .001) and for a longer period of time (median 122 days vs. 13 days; P = .003). The impressive results were obtained with strict eligibility criteria. The study excluded patients with radiosensitive tumors, neurologic deficits for 24 hours, multiple spinal tumors, lesions only compressing spinal roots, and prior RT to the vertebrae. Although studies demonstrated high efficacy of surgery, the formidable complications related to surgery cannot be overlooked. Using the Nationwide Inpatient Sample all-payer database, Patil et al569 reviewed data of more than 26,000 patients who had undergone surgery for spinal metastases. The in-hospital mortality and complication rates were 5.6%
and 22%, respectively. The most common complications were pulmonary (6.7%) and hemorrhages or hematomas (5.9%). Clearly, careful individual patient selection based on life expectancy and overall health is warranted.
Radiation Therapy
Traditionally, EBRT has been the main form of treatment for spinal metastases. In the modern surgery era, RT alone is often not sufficient in achieving decompression or stabilization (see above), but it is routinely used as adjuvant therapy following surgery as it is difficult to obtain wide
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most studies posed an interval of 1 to 3 weeks between resection and subsequent RT.570
An excellent response to RT alone for spinal compression was reported by Marazano and colleagues.571 Three hundred patients were randomized to a short-course (8 Gy x 2 days) or split-course (5 Gy x 3 days; 3 Gy x 5 days) schedule. After RT, 35% of nonambulatory patients regained walking ability, and pain relief was recorded in 57% of patients with a median survival of 4 months. Efficacy of RT was highly dependent on the histology: 70% of patients with nonambulatory breast cancer recovered mobility compared to only 20% of hepatocellular carcinoma patients. In general, solid tumors are considered either moderately radiosensitive (eg, breast and prostate cancers) or radioresistant (eg, melanoma;
osteosarcomas; cancers of the thyroid, colon, and kidney).572 On the other hand, hematologic malignancies such as lymphomas and multiple
myelomas are highly responsive to RT. Hence, RT alone is routinely utilized as therapy for these cancers, even in the presence of cord compression.
Where there is no compression, fracture, or instability, EBRT is effective in achieving local control as primary treatment. A mean 77% local control rate from seven retrospective studies including 885 patients was found in a systematic review by Gerszten and colleagues.572 RT is also a mainstay of palliative treatment for patients with poor PS, significant comorbidities, and/or limited life expectancy (<3–4 months). Klimo’s meta-analysis, including 543 patients treated by RT, revealed pain control rates of 54% to 83%.566 Unlike surgery, RT has no immediate significant treatment-related complications and very few local recurrences. However, it increases surgical complications as it impairs wound healing.
Stereotactic radiation approaches (SRS or stereotactic body RT [SBRT]) allow precise high-dose targeting in one or two fractions while minimizing
exposure of the surrounding cord.573 This is especially important in pre-irradiated patients. A review including 59 publications with 5655 patients who received SRS for spinal metastases showed 1-year local control rates of 80% to 90% for newly diagnosed disease, 80% following surgery, and 65% for previously irradiated disease.574 Single-institution reports suggest that SRS is safe and offers more durable response than conventional therapy,572,575,576 and results of the phase II RTOG 0631 trial demonstrated the feasibility of SRS for these patients.577 The phase III component of this trial is ongoing and is comparing single-dose stereotactic RT of 16 Gy to single-dose EBRT of 8 Gy in patients with one to three spinal metastases (NCT00922974). Consensus guidelines should be followed for stereotactic radiation planning and delivery.573,578,579 Reasonable dosing schedules for the postoperative setting have been published by Redmond et al.579 Vertebral Augmentation
Percutaneous vertebroplasty and kyphoplasty involve injection of cement (polymethyl methacrylate) into the vertebral body. Vertebroplasty is a direct injection, while kyphoplasty involves inserting a balloon that provides a cavity for the injection. These vertebral augmentation procedures immediately reinforce and stabilize the column, thereby relieving pain and preventing further fractures.580 They are suitable in poor surgical candidates with painful fractures, but are relatively contraindicated in the case of spinal cord compression because they do not achieve decompression. Symptomatic complications occur in up to 8% of patients (mostly with vertebroplasty), including embolization of the cement and local metastasis along the needle tract.
Systemic Therapy
Corticosteroids remain a routine initial prescription for patients presenting with cord compression, with a number of theoretical benefits including anti-inflammation, reduction in edema, short-term neurologic function
improvement, and enhanced blood flow. However, the preference between
Version 5.2020 © 2021 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-49 high-dose (96 mg daily) and low-dose (10–16 mg daily) is still unclear.
581-583
Chemotherapy has a limited role in metastatic spinal tumors except for chemosensitive tumors such as lymphoma, myeloma, and germ cell tumors. Agents efficacious for the primary tumor are used.
NCCN Recommendations Workup
Initial workup depends on the presence or absence of symptoms. Patients with an incidental, asymptomatic, metastatic lesion confirmed by systemic imaging can be observed with MRI. However, biopsy and further treatment of an incidental lesion are indicated if treatment of the patient is altered as a result of treatment of the incidental lesion. In the absence of symptoms, it is not mandatory to obtain a spinal MRI for every incidental metastatic lesion seen on surveillance bone scans. The alternate category involves severe or new back pain. Increasing intensity, duration, and changes in the character of pain should trigger an evaluation with an MRI study, even in patients with pre-existing degenerative spine conditions. Immediate spinal MRI is warranted in the occurrence of neurologic symptoms including weakness, paresthesias, and bladder or bowel incontinence.
Contrast can be used to highlight and further evaluate any focal abnormality. The MRI can be used to image the entire spine or a focal area of interest. If the patient is unable to have an MRI, then a CT myelogram is recommended.
A normal neurologic examination implies that there is no spinal
radiculopathy or myelopathy correlating with the patient’s symptoms. In this case, other causes should be considered (eg, leptomeningeal disease). An abnormal neurologic examination includes motor
abnormalities, sphincter abnormalities, and/or sensory deficits attributable to a dysfunction of nerve root(s) and/or the spinal cord. Therefore,
detection of radiculopathy, myelopathy, or cauda equina syndrome is indicative of an abnormal examination. However, reflex asymmetry and/or presence of pathologic reflexes, as well as sensory deficits of a
stocking/glove distribution are excluded.
Treatment
Once metastatic vertebral involvement is diagnosed, treatment is based on whether the patient is suffering from spinal cord compression, fracture, or spinal instability. In the presence of multiple metastatic spinal tumors, the one causing the patient’s main symptoms is addressed first. Additional tumors can be treated at a later point according to the algorithm.
Radiographic spinal cord compression implies deformation of the spinal cord because of epidural tumor, retropulsed bone fragment, or both. It should be noted that epidural tumor may occupy part of the spinal canal with or without partial obliteration of CSF around the spinal cord. Those cases are excluded because there is no cord deformation. For tumors occurring below L1, any canal compression of 50% or more should be considered of equal importance as spinal cord compression. Patients with radiographic cord compression should start on dexamethasone (10–100 mg) to alleviate symptoms. Decompressive surgery (concomitant
stabilization if indicated) and adjuvant RT is the preferred treatment (category 1) where there is spinal instability and no surgical
contraindication. Primary EBRT alone is appropriate for patients with radiosensitive cancers (hematologic malignancies) and without evidence of spinal instability. Many fractionation schemes are available (8 Gy in 1 fraction, 20 Gy in 5 fractions, or 30 Gy in 10 fractions); the most common is a total of 30 Gy in 3-Gy daily fractions for 10 days.584,585 Tolerance at the spinal cord and/or nerve route must be considered in determining dose.
Primary chemotherapy is also an option for chemo-responsive tumors in the absence of clinical myelopathy. In general, a treatment interval of at least 6 months is recommended.
Version 5.2020 © 2021 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. MS-50 Metastases to the spine without cord compression include the presence of
tumor in the vertebral body, pedicle(s), lamina, transverse, or spinous process. It can also include epidural disease without cord deformation.
Patients in this category should be assessed for fractures and spinal instability. Because the criteria for spinal destabilization secondary to tumor remain unclear, consultation by a surgeon is recommended. Spinal instability is grossly defined as the presence of significant kyphosis or subluxation (deformity) or of significantly retropulsed bone fragment. Not every pathologic fracture implies unstable structure. The degree of
kyphosis or subluxation compatible with instability depends on the location of the tumor in the spine. The cross-sectional area of the vertebral body unaffected by the tumor and the patient’s bone mineral density are
additional factors affecting stability. In addition, vertebral body involvement is more important than dorsal element involvement with regard to stability.
Circumferential disease as well as junctional and contiguous tumor location should be taken into account when assessing spinal stability. If fracture or instability is detected, the patient should undergo surgical stabilization or minimally invasive vertebral augmentation to relieve pain.
These procedures should be followed by adjuvant RT to obtain local control.
If no fracture or instability is found, EBRT is the treatment of choice.
Stereotactic RT may be appropriate in select cases of limited disease.
Other alternatives are chemotherapy for responsive tumors, or surgery plus adjuvant RT in select cases. Patients experiencing intractable pain or rapid neurologic decline during RT should consider surgery, or stereotactic RT is an option if oligometastases are present or if the disease is
radioresistant. Neurologic deterioration is apparent when the patient’s neurologic examination is becoming worse on a daily basis and the
patient’s ambulatory status is threatened. Intractable pain means that pain is not controlled with oral analgesics or that the patient cannot tolerate the medication due to side effects.
Progression and Recurrence
Follow-up involves MRI or CT imaging within 1 to 3 months
post-treatment, then every 3 to 4 months for 1 year, then as clinically indicated.
Upon detection of progression or recurrence on imaging scans, management strategy is based on previous treatment. Patients who underwent prior RT or surgery plus adjuvant RT may consider surgery or re-irradiation to the recurred area. Stereotactic RT may be appropriate for select patients. Clinicians should plan 6 months or more between
treatments in consideration of tolerance of the spine and its nerve roots.
Retreatment dose should be limited to no more than 10 Gy to the surface of the spinal cord. In patients who were previously treated with
chemotherapy, surgery may be indicated depending upon the degree of spinal stability/cord compression. RT may also be considered.
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