Ms H and Dr O were interviewed by a Perspectives editor.
MS H: I was diagnosed with breast cancer in December of 1985. I had a mastectomy in January of 1986. I did chemotherapy for 8 sessions. I followed that with radiation. In 1990, I had metastases in my left hip and in a rib. They removed that rib. They took my ovaries out, and the one in my left hip went away. Then in 1990, I had [a bone scan], and they found a metastasis in my spine. So, they radiated my spine. Then in 2003…I had a tumor, metastatic disease, in T7. They irradiated that and my spine became unstable. My doctor, Dr L, took out that vertebra and fused me. The tumor returned, and it was pressing against my spinal cord. My doctor didn't feel that he could handle the surgery and wanted me to go to Dr O,…and my doctor actually flew up to do the surgery with Dr O.
I was lying around…not doing a lot, so I started to atrophy…I didn't go to work…My social activities were cut to nothing, and I'm a very active person. I didn't go to basketball games, and I missed a football game. I just couldn't go.
DR O: [She] had been a very active woman. Unfortunately, with her tumor's progressive involvement of the spine, and her progressive deformity, she became disabled to the point where she was not really able to ambulate around the house…She was only 55 years old, and she was really losing her independence. This is always an issue, even for older patients, but for someone this age, this is a very difficult thing.
About 500 000 patients die of cancer annually. Ms H is among the 12 700 cancer patients in the United States who, each year, develop spinal cord compression, putting them at risk for pain, paraparesis or paralysis, incontinence, and institutionalization.1 Breast, prostate, and lung cancer each account for 15% to 20% of cases; non-Hodgkin lymphoma, myeloma, and renal cell carcinoma each account for 5% to 10% of cases. The remainder are primarily from colorectal cancer, cancer of unknown primary, and sarcoma.2,3
Malignant cells reach the spinal canal (1) through arterial spread, (2) through venous drainage from the valveless veins of Batson's plexus that communicate with the venous drainage from numerous organs, (3) in the cerebrospinal fluid, or (4) through direct extension either through the vertebral foramina (as occurs in patients with lymphoma) or from a metastasis breaking out of a vertebral body. As is true for other metastases, the frequency with which certain tumors cause spinal metastases may be due to their particular surface proteins and adhesion molecules.4
Assessment of the Patient With Spinal Cord Compression
MS H: At first it was just pain. After they diagnosed it, it gradually got worse. I started getting numbness in my feet and by the time I [flew] up to my surgery, they were practically carrying me through security. I could hardly even walk.
DR O: When she came to see me, she had progressive pain as well as difficulty walking [and] difficulty sitting…[In] a patient presenting with a new onset of [back] pain, especially a patient with a history of tumor, we always have to have tumor very high on our differential diagnosis.
Back pain is the most common symptom of spinal cord compression, noted by 83% to 95% of patients before its diagnosis.3,5 Pain, which can be local, referred, radicular, or all 3, is caused by the expanding tumor in the bone, bone collapse, or nerve damage. Referred pain is common: cervical compressions often cause midscapular pain, thoracic compressions can cause hip or lumbosacral pain,6 and lumbosacral compressions can cause thoracic pain.7 Sixty percent of the metastases are thoracic, 30% lumbosacral, and 10% cervical.3 Commonly, breast and lung cancers cause thoracic lesions, whereas colon and pelvic carcinomas affect the lumbosacral spine.8 In 20% of patients, cancer presents as a spinal cord compression.6,9
Patients with cauda equina syndrome experience diminished sensation over the buttocks, posterior-superior thighs, perineal region, and, in 20% to 80%, decreased anal sphincter tone. Urinary retention and overflow incontinence are pathognomonic of the syndrome (90% sensitivity and 95% specificity).10 Absence of a postvoid residual virtually excludes it (99.99% negative predictive value).10
Common signs of spinal cord compression include radiculopathy, weakness,11 sensory changes (eg, paresthesias, loss of sensation), sphincter incontinence, and autonomic dysfunction (eg, urinary hesitancy, retention). One useful scale for functional assessment is the Frankel grading system,12 which consists of (A) complete paraplegia, (B) only sensory function, (C) nonambulation, (D) ambulation, and (E) no neurological symptoms or signs. Other scales include the Frankel/American Spinal Injury Association scale,13 the International Medical Society of Paraplegia scale,13 and the Tomita scale.14 The Barthel index, originally designed for geriatric patients, additionally assesses transfer from bed to chair or commode and bowel and bladder function.15
It is difficult to determine the current prevalence of these signs of spinal cord compression because most studies were conducted before diagnosis by magnetic resonance imaging (MRI) became available. In 1 study, 60% to 85% of patients at diagnosis had weakness and two-thirds were nonambulatory.3 In others, more than half presented with sensory changes beginning in the toes16 or 1 to 5 levels below the lesion.3 About half needed Foley catheters,3 but autonomic dysfunction was never the sole presenting symptom.8,16
Diagnosis of Spinal Cord Compression
DR O: Her main risk for mortality was progressive paraplegia…The real risk factors here are infection problems, pulmonary problems, skin problems—that's what leads to death in many of these cases, even more so than the progression of the tumor itself.
Delay in diagnosis of spinal cord compression results in loss of mobility,17,18 bladder dysfunction,17 and decreased survival.19-23 Because therapy is usually well tolerated in ambulatory patients (even those with limited overall prognoses),24 the diagnosis of spinal cord compression should always be considered urgent.
Magnetic resonance imaging is the criterion standard in detecting epidural metastatic disease and frank spinal cord compression5,20,25,26 (sensitivity, 93%; specificity, 97%; and overall accuracy, 95%).27 Plain spine radiographs have inadequate sensitivity and a false-negative rate of 10% to 17%.3 No validated predictive models suggest that clinicians can omit an MRI in a patient with known cancer and back pain.28
Finding unsuspected lesions is not unusual.6,29,30 In 45% of patients, MRI findings altered the radiation therapy field.31 An MRI of the entire spine is therefore required, including T1-weighted sagittal images with T1- or T2-weighted axial images in areas of interest.3,20,32 Because patients with prostate cancer who have had more than 20 bone metastases and who have taken hormone therapy for several years have a 44% incidence of spinal epidural disease, MRIs might be considered even before the development of symptoms of spinal cord compression.5
Treatment of Spinal Cord Compression
MS H: All I care about is walking and living my life.
DR O: For many patients, reasonable goals are improvement of pain, improvement of quality of life, improvement of independence. For [other] patients, the goal is to improve survival. Understanding exactly what the patient's goals are and understanding the clinical scenario are important for an appropriately guided treatment…What is somebody's quality of life? We break it up into domains that include pain, function, social role, self-image, mental health, physical health, and overall quality of life. This patient had significant compromise in each of these domains before the surgery, and our goal with surgery was to both improve the quality of life and, with tumor surgery, to try to improve survival.
Pain Management and Symptomatic Measures
MS H: The pain was under control; I had a fentanyl patch and [hydromorphone].
Table 10-1 lists common opioids and adjuvants that control neuropathic and bone pain from vertebral metastases and spinal cord compression.3,7,35,36 Opioid dosages shown are for opioid-naive patients; those already taking opioids may need substantially higher dosages. Patients who have moderate or severe pain often benefit from a continuous intravenous infusion of opioids administered through a patient-controlled analgesia device, which allows the patient to self-administer rescue doses should the initial basal rate chosen be inadequate or should pain occur with movement (so-called incident pain). A consensus document from the American Pain Society offers algorithms for safe titration of intravenous opioids.36 Corticosteroids, effective for both neuropathic and bone pain, are discussed below. The anticonvulsants gabapentin and pregabalin have been shown to decrease the paresthesias and the burning, shooting, "toothache" pain that arises from peripheral nerve or spinal cord injury,7,34,37,38 although no studies have specifically investigated patients with malignant spinal cord compression. To minimize sedation, both agents should be started at a low dose and titrated to effect (Table 10-1). Tricyclic antidepressant agents, which putatively act via a different mechanism than anticonvulsant agents,34 can be used at bedtime because most induce sedation.7,34 Although no randomized trials have investigated the effects of anticonvulsants in patients with malignant spinal cord compression, a single randomized controlled trial involving patients with spinal cord injury (from unspecified causes) showed that amitriptyline was no more effective than placebo.39
Table 10-1Pharmacologic Management of Pain in Opioid-Naive Patients With Malignant Spinal Cord Compressiona |Favorite Table|Download (.pdf) Table 10-1 Pharmacologic Management of Pain in Opioid-Naive Patients With Malignant Spinal Cord Compressiona
|Drug ||Initial Dose for Opioid ||Comments |
|Opioids || || |
| Morphineb || || |
| Immediate release ||15-30 mg orally every 2 h as needed ||Titrate to relief |
| Sustained release ||15 mg orally every 8-12 h ||Increase every 24 h based on need |
| Oxycodoneb || || |
| Immediate release ||10-20 mg orally every 2 h as needed ||Titrate to relief |
| Sustained release ||10 mg orally every 12 h ||Increase every 24 h based on need |
| Hydromorphone |
| Immediate release ||4-8 mg orally every 4 h as needed ||Titrate to relief; add sustained release opioid or fentanyl for basal relief |
| Fentanyl ||12-25 μg/h transdermally every 72 h ||Add immediate release opioid as needed every 2-4 h |
|Neuropathic pain adjuvants || || |
| Dexamethasone13,33 ||10 mg orally or intravenous load, 4-6 mg orally or intravenously every 6 h ||Current practice; in patients with symptomatic compression, evidence favors higher doses (see text for discussion) |
| Gabapentin34,b,c ||100 mg orally twice a day; 300 mg at bedtime ||Can cause somnolence, edema, and myoclonus |
| Pregabalin34,b,c ||75 mg orally twice a day ||More reliable oral absorption than gabapentin |
| Amitriptyline, nortriptyline34,d ||10-25 mg orally at bedtime ||Second-line therapy, anticholinergic adverse effects |
|Bone pain adjuvants || || |
| Zoledronic acid13 ||4 mg intravenously every 3-4 wk ||Hypocalcemia occurs in patients with vitamin D deficiency |
| Pamidronate13 ||90 mg intravenously every 3-4 wk ||May have less renal toxicity |
| Acetaminophen ||1000 mg orally every 6-8 h || |
|Bowel regimen medicationse || || |
| Docusate plus senna ||1-2 orally twice a day ||Use in most patients taking opioids |
| Polyethylene glycol ||17-34 g orally at bedtime as needed ||Used when no stool in 48 h |
| Bisacodyl or glycerin suppository ||Daily, scheduled ||To empty bowel in patients with severe autonomic dysfunction, suppository followed by enema as needed |
Aggressive treatment of constipation due to autonomic dysfunction, inactivity, or opioids will prevent increased pain from use of the Valsalva maneuver.3,7,36 For patients who retain sphincter control, a typical initial regimen would include a stool softener, a stimulant, and an osmotic laxative to promote soft stooling at least every 1 to 2 days (Table 10-1). For patients who cannot eliminate stool on their own, a regimen of polyethylene glycol and a daily stimulant suppository is effective.7
Bisphosphonates, such as zoledronic acid and pamidronate, decrease bone pain.7,13 Nonsteroidal anti-inflammatory agents are safest for younger patients who have no history of gastrointestinal bleeding and normal renal function. They may be added for patients who poorly tolerate opioid-induced adverse effects.7,35,36 Physical therapy will not diminish the pain related to tumor or pathologic fracture and may accentuate fracture pain, so it should not be used before radiation or surgery. Braces, however, may improve comfort by providing external support.
Patients with paraparesis or paralysis frequently experience anxiety and depression.40 Patients whose core self-image and sense of self-esteem are predicated on physical activity and independence may find themselves feeling out of control, helpless, and hopeless. They and their families need referrals to social workers, psychologists, psychiatrists, or spiritual leaders.
DR O: She was on high doses of steroids…When she came to see me, she had progressive pain as well as difficulty walking. Even walking inside her house, she needed support. She also had difficulty sitting. She was spending most of her day in bed.
Glucocorticoids reduce injury from traumatic spinal cord injury41 presumably through their antioxidant or antioxidant-like activity, reducing the release of total free fatty acids and prostanoids and preventing lipid hydrolysis and peroxidation.41 Dexamethasone inhibits prostaglandin E242 and vascular endothelial growth factor production and activity43 and therefore decreases vasogenic edema, which is partially mediated by increased levels of prostaglandin E244 and vascular endothelial growth factor.45 Animal models indicate a dose-dependent response of vasogenic edema and improved neurologic function with corticosteroids, even without radiation therapy.46-48
Although some experts believe that dexamethasone does not benefit asymptomatic ambulatory patients receiving radiation therapy,20,24,49,50 the general consensus is that corticosteroids are beneficial.13,24 Prospective studies suggest an initial dexamethasone dose of 96 or 100 mg of intravenous bolus followed by 24 mg taken orally every 6 hours for 3 days, tapered over 10 days.11,51 Of patients so treated, 64% reported substantial relief on day 1 and 82% reported overall relief.11 In a randomized, single-blind trial, 57 patients receiving radiation therapy were randomized by diagnosis (breast cancer or other) and gait function (preserved or not) to receive either high doses or no doses of dexamethasone. At the end of therapy, 22 of 27 patients taking dexamethasone were ambulatory compared with 19 of 30 who did not (P = .046).51
High-dose dexamethasone to promote posttreatment ambulation was a grade A recommendation from a 1998 evidence-based guideline.49 However, the guideline acknowledged that the optimal dose of dexamethasone is unknown.20,25,52 This remains the case a decade later, but given the anxiety, restlessness, and delirium that high doses of dexamethasone can induce,53 an initial dexamethasone dose of 24 to 40 mg/d orally or intravenously (eg, 6 to 10 mg every 6 hours), with a taper during or immediately after completion of radiation, is reasonable.13,33
Even at these lower doses, 5% of 21 patients receiving less than 3 weeks of therapy experienced tremulousness, insomnia, delirium, and hyperglycemia.52 Toxicity increased when the total dose exceeded 400 mg and when treatment extended for more than 3 weeks.52 Fourteen of 38 patients (37%) on the prolonged steroid course developed oral or esophageal Candida infections.52 If a prolonged course of dexamethasone is planned, simultaneous trimethoprim and sulfamethoxazole to prevent Pneumocystis jiroveci infection54 and 100 mg of fluconazole taken orally daily to prevent thrush and esophageal candidiasis should be considered.
MS H: My most worrisome thing right now is that I have to still have radiation…to my spine, and your spinal cord can only take so much without you being paralyzed. So, I'm very, very anxious about this.
Radiation therapy is directed at vertebral metastatic sites that are painful or are associated with significant epidural involvement or thecal sac indentation (ie, subclinical spinal cord compression). Prospective observational studies have shown that 60% to 90% of patients achieve pain relief with radiation therapy and dexamethasone.2,21,55,56 From 60% to 100% of patients who are ambulatory before radiation therapy maintain the ability to walk.2,11,19,2055 Patients with lung cancer are least likely to remain ambulatory.2,3 Pooled studies indicate that 36%30-32,34-44 to 40%32,34-51 of paraparetic patients become ambulatory after radiation therapy.19,21 Restoration of full ambulation and sphincter function ranges from 13%8-21 to 15%9-24 of paralyzed patients.19-21 More than 50% of patients with lung cancer and 40% with prostate cancer remained paralyzed vs 10% of patients with breast cancer (P = .003).19
Radiation therapy ports extend 1 or 2 vertebral bodies above and below the site of compression.16 Myelosuppression can occur if multiple spinal sites are treated.57 Dosing schedules are designed to have a less than 5% chance of inducing radiation myelopathy (eg, hemiparesis, spasticity, and loss of pain and temperature sensation). Standard external beam radiation therapy usually consists of 30 Gy in 10 fractions49; regimens of more than 30 Gy do not improve outcomes.58 However, treatment regimens can be more prolonged (25-40 Gy in 10-20 fractions over 2-4 weeks)16; treatment courses can also be shorter (4 Gy/d for 7 days)19,33 or much shorter (8 Gy once or 4 Gy for 5 sessions or 8 Gy for 2 sessions 1 week apart).57,59,60 The preliminary data from a multinational, nonrandomized study of 231 patients comparing short-course radiation therapy (1 × 8 Gy in 1 day or 5 × 4 Gy in 1 week) with longer-course radiation therapy (10 × 3 Gy in 2 weeks, 15 × 2.5 Gy in 3 weeks, or 20 × 2 Gy in 4 weeks) suggested similar efficacy between short- and long-course radiation therapy on posttreatment motor function.61 After balancing significant pretreatment prognostic factors, no regimen has been shown to be superior in preserving ambulation.20,25,62,63
No late radiation-related toxic effects have been reported using short courses,19,60,62,64 but patients develop more in-field recurrences, less bone recalcification,62 and shortened survival compared with patients receiving longer courses.4,63,65,66 Nevertheless, shorter courses are safe and effective and may be particularly appropriate for patients with shorter life expectancy who can achieve pain control and preserve their ambulatory status.4,63
Overall, 10% of patients treated with standard radiation therapy develop recurrences in the short term (median time to recurrence, 4.5 months),19 but 50% of 2-year survivors and almost all 3-year survivors develop recurrences.3 For patients who initially received a short course of therapy, a repeat course of external beam radiation therapy (or stereotactic radiosurgery) can be considered.20 Patients who experience a recurrence have a median survival of 4.2 months, but of those who survive, 88% remain ambulatory at 6.5 to 35 months. Radiation-induced myelopathy rarely develops (eg, 1 of 13 long-term survivors60), with a median latency of 1 to 2 years.67 Therefore, for patients likely to survive less than 1 year, the benefits of subsequent irradiation likely exceed the risks.
High-Precision Radiotherapy Techniques
DR O: The CyberKnife…allows for a tremendous ability to give controlled doses of radiation in a spatially focused way. So, we can effectively spare the spinal cord and spare the structures around the spine.
Advances in radiation therapy techniques show promise both for primary treatment and for patients with recurrent disease. With the evolution in computed tomography and MRI capabilities, conformational radiation therapy plans are now 3-dimensional, and, with the advent of intensity-modulated radiotherapy (IMRT) (the ability to vary dose administered during a treatment session), higher radiation doses can now be administered to the target, sparing normal spinal and paraspinal tissues.68 Image guidance with IMRT is a further refinement.69 Tomotherapy is a third high-precision technique that uses a rotating linear accelerator to deliver IMRT.68
Patients with oligometastatic disease (defined as involvement of ≥ 3 vertebrae and no other bone or visceral metastases) may also benefit from high-precision radiation therapy because these patients have an excellent prognosis with radiation therapy alone. In a retrospective series of 521 patients with squamous cell carcinoma and oligometastatic disease receiving radiation therapy alone, motor function improved in 40% of patients and remained stable in another 54%.64 After radiation therapy, 54% of nonambulatory patients became ambulatory, and 94% of initially ambulatory patients remained ambulatory. Local control and survival rates at 1 year were 92% and 71%, respectively. Myeloma and lymphoma patients with a slow (> 14 days) development of motor deficits before radiation therapy had the best prognosis. None of these patients showed progression of motor deficits, and all patients were ambulatory after radiation therapy. One-year local control was 100%, and 1-year survival was 94%. These patients appear well treated with radiation therapy alone. However, the results were obtained from retrospective data, and proper randomized trials are lacking.
Stereotactic radiosurgery (eg, the CyberKnife68 or the Novalis Shaped Beam Surgery67) can be used alone or after external-beam radiation or surgery, as it was for Ms H.70 Patients receive 1 large dose (eg, 6-8 Gy) to a localized tumor with the precisely shaped radiation beam that comes as close as 1.36 mm to the simulation isocenter.71 Patients must be able physically and emotionally to tolerate staying in the same position for the 90 minutes of the treatment.63,72 Patients who have radiosensitive tumors (eg, myeloma, lymphoma), more than 25% spinal canal compromise and significant cord compression, less than 5 mm between the cord and the tumor, or spinal instability are not eligible for stereotactic radiosurgery or stereotactic body radiation therapy.63 As is true for standard spinal radiation, concurrent therapy with agents that act as radiosensitizers (tyrosine kinase or epidermal growth factor receptor inhibitors) or certain chemotherapeutic agents (such as the taxanes or antiangiogenic agents) must be avoided. It is not clear when they can be resumed because they may cause the "recall" phenomenon (ie, as though radiation were again being given, these therapies may cause the patient to develop the toxic effects they experienced from the radiation).63
When used alone (without spinal tumor resection), radiosurgery provided pain relief in 74%73 to 89%74,75 of patients followed up prospectively for 14 to 48 months.74 None developed spinal instability or neurologic defects, even though 12% later required surgery for progressive tumor.74 One prospective cohort study of 500 patients followed up for a median of 21 months (range, 3-53 months) analyzed the outcomes of radiosurgery in patients without "bony compression of neural elements or overt spinal instability."75 Long-term pain control was achieved in 86% overall, in 96% of patients with breast cancer or melanoma, and in 93% of patients with lung cancer. Tumor progression was halted in 90% of the 65 patients receiving radiosurgery for primary treatment (100% of breast, lung, and renal cell carcinoma and 75% of melanoma) and in 90% of the 51 patients treated after failure of conventional irradiation (100% of breast and lung carcinoma, 87% of renal carcinomas, and 75% of melanomas).75 Few studies to date have directly compared the efficacy and toxicity of radiosurgery and conventional radiation therapy. One retrospective matched-pair analysis of patients with spinal metastases from metastatic breast cancer showed similar ambulation, performance status, and pain control in 18 patients with initial spinal disease who received CyberKnife radiosurgery and 17 patients who underwent repeat radiation therapy for recurrent disease.76
Although this focused radiation therapy is effective, concerns have been raised that the precision may pose a problem in patients expected to have prolonged survival.77 Tumor progression was found in 16% of patients 1 year after stereotactic body radiation therapy for metastases in the spine.78 Primary patterns of failure were locally in the bones or into the epidural space. Hartsell and Sweeney77 have asked, "How is bone stability affected by stereotactic body radiation therapy? Will more patients require surgical fixation or stabilization of the bone with higher doses?"
Insurance coverage for radiosurgery is generally available for patients requiring repeat irradiation but may be more problematic for initial therapy. Given the cost of stereotactic body radiation therapy, which is much greater than short-course radiation therapy, stereotactic therapy might be reserved for patients whose tumor type (eg, melanoma, renal cell, or sarcoma) requires much larger doses of radiotherapy.4,79 Further studies comparing radiosurgery with traditional radiotherapy are needed to determine its effectiveness and the highest tolerable doses.71,80
DR O: [O]ur goal was to improve her pain and deformity…We can reliably stabilize the spine and that will improve pain, as well as stance and alignment of the spine…She'd already had her maximum tolerable dose of radiation, and despite radiation, she had progression of tumor…The deformity would continue to get worse over time…In this setting, with the tumor in the epidural space and a revision surgery, we're unable to get all the tumor out. By getting a majority of the tumor out,…we were able to accurately localize where to go with radiation using the CyberKnife. It's important to recognize that there is a role for a multidisciplinary approach to the patient…We have neuroradiologists who put together some of the imaging. We have medical oncologists and radiation oncologists. We have our orthopedic team who does complex reconstructions…Having all of these components integrated in a setting where we are discussing cases and learning from each other is very valuable.
Debate is ongoing regarding the merits of radiotherapy alone vs surgical therapy followed by radiation for selected patients with spinal cord compression. Despite finding "few papers of high methodological quality,"25 a 2005 evidence-based review recommended radiation for ambulatory patients without spinal "instability," bony compression, or paraplegia on presentation; it recommended surgery for patients with progressive neurologic deficits, vertebral column instability, radioresistant tumors (lung, colon, renal cell), and intractable pain unrelieved by radiation therapy.19,25,49,81
Physicians must weigh the patient's health, ability to tolerate surgery, and goals of therapy. Surgeons generally agree that a life expectancy of more than 3 months is required for spinal surgery and use the scoring system developed by Tokuhashi et al82 to predict it (Table 10-2). In addition, patients should have adequate general health, as reflected by a Karnofsky performance score of more than 40%.83 Several trials have confirmed the accuracy of this scoring system, including patients with metastatic breast or renal cell cancers.83,84 The prognostic scoring system developed by Rades et al,66 developed from patients receiving radiation therapy, might be applicable as well.
Table 10-2Tokuhashi Revised Scoring System for Preoperative Prognosis of Metastatic Spinal Tumorsa |Favorite Table|Download (.pdf) Table 10-2 Tokuhashi Revised Scoring System for Preoperative Prognosis of Metastatic Spinal Tumorsa
|Parameter ||Score |
|General condition || |
| Poor ||0 |
| Moderate ||1 |
| Good ||2 |
|No. of extraspinal metastases || |
| ≥ 3 ||0 |
| 1-2 ||1 |
| 0 ||2 |
|No. of vertebral body metastases || |
| ≥ 3 ||0 |
| 2 ||1 |
| 1 ||2 |
|Metastases to the major internal organs || |
| Nonremovable ||0 |
| Removable ||1 |
| None ||2 |
|Primary site of cancer || |
| Lung, osteosarcoma, stomach, bladder, esophagus, pancreas ||0 |
| Liver, gallbladder, unidentified ||1 |
| Others ||2 |
| Kidney, uterus ||3 |
| Rectum ||4 |
| Thyroid, breast, prostate, carcinoid ||5 |
|Palsy or myelopathy || |
| Complete ||0 |
| Incomplete ||1 |
| None ||2 |
Before the 1980s, laminectomy was the generally accepted surgical approach, but it not only inadequately decompresses the spinal canal, it also potentially compromises vertebral column stability.85 Currently, surgeons use anterior (transthoracic and retroperitoneal) and posterolateral (costotransversectomy and lateral extracavitary) approaches for surgical decompression with reconstruction. In observational studies, 80% to 94% of patients obtained pain relief,81,86-88 68% to 75% of nonambulatory patients regained ambulatory status,81,88 and 50% of severely paraparetic patients became completely ambulatory.81
In 2005, Patchell et al88 published the first prospective, randomized trial comparing direct decompressive surgery followed by radiotherapy with radiotherapy alone in a carefully selected subset of patients. Patients had to have MRI evidence of metastatic epidural spinal cord compression restricted to a single contiguous area to be eligible, although they could have other noncompressive areas of epidural disease. Patients had to have a cancer origin other than central nervous system or spinal column, no prior history of cord compression or preexisting neurologic disease, at least 1 neurologic symptom (eg, pain) or sign, and, if totally paraplegic, symptoms for no longer than 48 hours before study entry.
Fifty patients were randomized to initial surgery, 3 of whom completed surgery but did not receive postoperative radiation. Fifty-one patients were randomized to initial radiation therapy (30 Gy in 10 fractions), 1 of whom required surgery because of deterioration of strength during radiotherapy. The study was discontinued at its midpoint due to the superior response of the group randomized to decompressive surgery plus radiation therapy. The posttreatment ambulation rate in those randomized to combination treatment was 84% vs 57% in those randomized to radiation therapy alone (P = .001; odds ratio, 6.2; 95% confidence interval [CI], 2.0-19.8]). Patients who were randomized to surgery plus radiotherapy retained ambulation for a significantly longer period than patients who were randomized to radiation alone (122 vs 13 days, P = .003), and 94% of patients who were ambulatory before surgery plus radiotherapy remained ambulatory, whereas only 76% of patients who were randomized to radiation alone did so. Maintenance of continence, functional scores, and survival were also significantly greater in the group randomized to surgery before radiation therapy. Importantly, the efficacy of radiation therapy alone in the study by Patchell et al 88 was far less than that seen in unselected patient series. Suggested explanations included exclusion of patients with highly radiosensitive tumors from the study,89 inclusion of fewer patients with more fast-growing and potentially radiosensitive tumors in the radiotherapy group,90 and a higher proportion of patients with vertebral body collapse or with nonneurologic morbidity in the radiotherapy group.91 The authors later provided data refuting the latter 2 explanations.92 They also performed a secondary data analysis indicating that surgery in these selected patients is most effective in patients younger than 65 years. In these patients, the odds of ambulating after surgery followed by radiation therapy were 5.14 times higher than in those receiving radiation alone (P = .002).93 Patients 65 years or older had only a 1.86 times greater odds of ambulating with surgery followed by radiation than with radiation alone.
Rates of surgical complications (eg, wound breakdown, failure of spinal stabilization, infection, excessive blood loss, respiratory failure, intra-abdominal vascular or visceral injury, or cerebrospinal fluid leak) range from 23% to 50%.81 Complication rates are significantly (P < .001) related to age older than 65 years vs younger than 65 years (71% vs 43%), history of prior radiation therapy (67% vs 33%), and paraparesis vs ambulatory status (64% vs 39%).85,87,94
A meta-analysis confirmed that patients with symptomatic spinal cord compression who underwent surgery (with or without preoperative or postoperative adjunctive radiation therapy) were 1.3 times more likely to be ambulatory (crude risk ratio, 1.28; 95% CI, 1.20-1.37; P < .001) than patients treated primarily with radiation.95 A later nonrandomized, multicenter, prospective observational study by the surgeons of the Global Spinal Tumour Study Group assessed outcomes of all patients with extradural (spinal) osseous metastases referred by their oncologists or other physicians to their 6 centers during 2 years for surgery for pain control, including quality of life, prevention of neurologic deterioration, or prevention or correction of spinal instability.96 Patients had a mean age of 61 years; 92% presented with pain, 24% with paraparesis, and 22% with urinary sphincter dysfunction. Two-thirds had a Karnofsky performance score of less than 80 and were unable to work or carry out their activities of daily living. Sixty percent of the patients had "widespread" spinal metastases; tumor type was breast, renal, lung, or prostate in 65%.
Twenty-six percent had preoperative radiation, 31% had preoperative chemotherapy, and 12% had both. After surgery, 45% received radiation therapy and 31% had chemotherapy. The 223 patients were followed up for 13 to 37 months postoperatively. Median in-hospital stay was 20 days (mean, 23 days; range, 3-88 days). Postoperatively, 71% had improved pain control; 64% improved or maintained their Frankel score. Of those who were not ambulatory, 53% regained mobility, and 39% of those with abnormal urinary sphincter function regained normal function. It was not clear whether some of those improvements were related to the preoperative therapies given, as would be expected for the 21% of patients with breast cancer. Nonetheless, this study clearly suggested benefit from en bloc or debulking surgery even for patients with solid tumors and multiple spine metastases. How these patients would have done with radiation therapy alone remains an unanswered question.
Although radiation remains the therapy offered to most patients,97 surgery is increasingly being offered to patients with metastatic spinal cord compression who fulfill the strict criteria of the study by Patchell et al.88 Given that these patients commonly require urgent surgery, the surgical teams at the tertiary cancer centers who perform these procedures may need to develop new systems to enable them to fit these complex reconstructive procedures into their surgical schedules.98
Chemotherapy and Hormonal Therapy
MS H: I think it's important for oncologists to not think that the patient isn't theirs when they go have surgery [but] to stay involved and maintain contact with the patient…My oncologist has been very involved and spoke with the surgeons and called me when I was recovering. He's been very involved in all of this. I think that this helps a patient feel safe.
Because the epidural space is on the systemic side of the blood-brain barrier, chemotherapy and hormonal therapies have been used in individual patients with spinal cord compression from Hodgkin and non-Hodgkin lymphomas,99,100 germ cell tumors,101 breast or prostate carcinomas, or neuroblastomas.3 In these individual case reports, the compression completely resolved in 5 of the 7 patients reported. No large case series or randomized controlled trials have been reported.
Prognosis of Patients With Spinal Cord Compression
DR O: The outcomes are different for patients with solitary metastases vs patients with widely metastatic disease. For somebody with widely metastatic disease, in general, our focus is on improving health-related quality of life…We're not affecting the natural history of the tumor. We improve mortality by improving ambulation and the comorbidities that can occur with progressive loss of function.
MS H: I know that cancer is going to get me eventually. I have a nodule in my lung that I'm not even thinking about right now. I'm not worrying about it right now. I just don't get into that prognosis stuff. All I care about is walking and living my life. I'm more interested in quality than quantity.
Pretreatment ambulatory status and time from development of motor deficits to radiotherapy are the most important predictors of ambulation after treatment,62,102-104 place of care, and bladder function.105 Overall, 75% to 100% of ambulatory patients remain ambulatory,3,20,55 and 50% of those who survive 1 year are still ambulatory.3 Approximately 14% to 35% of paraparetic and 15% of paralyzed patients regain useful function after radiation therapy.5,20 Patients with cancer who develop spinal cord compression spend twice as many days in the hospital during the last year of life compared with those without spinal cord compression.1 Of patients who were fully ambulatory at diagnosis, 64% were at home at 1 month after diagnosis, 27% were hospitalized, and 9% were in a hospice facility. Of those who initially required assistance, only 37% were at home, 48% were hospitalized, and 15% were in hospice facilities at 1 month; of those who could not walk, 31% were at home, 36% hospitalized, and 33% were living in hospice facilities. Normal bladder function was retained in 69% of the fully ambulatory at diagnosis, 61% of those requiring assistance, but only 33% of those who were not ambulatory.105 However, no matter how disabled, mood was normal in most patients, few had moderate or severe anxiety or depression, and most reported that their lives still contained both quality and meaning.105
Median survival after spinal cord compression depends on the patient's tumor type, ambulatory status, and number and site of metastases.65,96,102-105 Patients with a single metastasis, a radiosensitive tumor, or myeloma, lymphoma,105 breast, or prostate cancer have the longest survival,3,19,59,106 whereas patients with multiple metastases, visceral or brain metastases, or lung or gastrointestinal cancers have the shortest.3,19,81,105 Even patients with responsive tumors, such as myeloma, lymphoma, and breast cancer, have relatively short median survivals of 6.4, 6.7, and 5 months, respectively; survival of patients with prostate or lung cancer is only 4 and 1.5 months, respectively.1 One-year survival rates for patients with spinal cord compression due to multiple myeloma, lymphoma, and breast and prostate cancers were 39%, 38%, 27%, and 22%, respectively, whereas that of lung cancer patients was 4%.1
Retrospective and prospective observational studies demonstrate that median survival for patients who could walk after the completion of therapy was 7.9 to 9 months, but median survival for nonambulatory patients was only 1 to 2 months.19,21,22 In 1 prospective study of 319 patients, those who were fully ambulatory at diagnosis had a median survival of 151 days (95% CI, 80-222 days), those requiring assistance had a median survival of 71 days (95% CI, 46-96 days), and those unable to walk had a median survival of 35 days (95% CI, 26-44 days).105
Rades et al66 developed an instrument called the First Score, which predicts survival of patients receiving radiation therapy alone, developed from a multivariate analysis of 1852 patients with metastatic spinal cord compression. The 6 factors significantly associated with survival were tumor type, other bone metastases, visceral metastases, interval from tumor diagnosis to metastatic spinal cord compression, preradiation therapy ambulatory status, and time developing motor deficits before radiation therapy. Variables associated with a short prognosis included primary tumors other than breast, prostate, or myeloma and lymphoma; other bone or visceral metastases; nonambulatory status before therapy; interval from tumor diagnosis of less than 15 months; and motor deficits developing less than 14 days before therapy.65,66 The score for each prognostic factor was determined by dividing the 6-month survival rate (given in percentage) by 10. Total scores represented the sum of the 6 scores obtained for each prognostic factor. Five scoring groups were defined: 20 to 25, 26 to 30, 31 to 35, 36 to 40, and 41 to 45 points. The 6-month survival rates were 4% for patients with 20 to 25 points, 11% for those with 26 to 30 points, 48% for those with 31 to 35 points, 87% for those with 36 to 40 points, and 99% for those with 41 to 45 points (P < .0001).
Patients not likely to live long enough for a recurrence or bone recalcification are the best candidates for single fraction or short-course radiation therapy. Subgroup analyses showed that patients with at least 36 points had significantly improved survival with longer-course than short-course radiation therapy. Patients with scores less than 36 points had similar survival with short-course or longer-course radiation therapy. Thus, patients with at least 36 points should receive longer-course radiation therapy, and those with less than 36 points should receive short-course radiation therapy.107
The medical oncology team can help patients with spinal cord compression decide which mode of therapy, if any, is appropriate for them by exploring the patient's goals, the likely outcomes of each therapy (eg, pain relief or preservation or return of function), the beneficial and adverse effects of therapy, the likely duration of inpatient and rehabilitation stays, and the estimated survival times with and without therapy. For patients like Ms H, aggressive palliative surgery plus radiation therapy will markedly improve the quality of the time remaining. Arranging a multidisciplinary consultation with a radiation oncologist and a surgeon can help patients and families make their best choice.
DR O: It's important to help the patient make informed choices and understand exactly what kind of effect this surgery is going to have on their life and what their needs will be after surgery. They will need immediate rehabilitation. We try to identify what kind of resources the patient will have among family and friends and try to mobilize those resources and try to optimize what's available to the patient…The rehabilitation centers have specialists in rehabilitative medicine. We communicate extensively with them in regard to what sort of activities might be restrictions for the patient and to determine if there might be a brace required. We also discuss what the goals of recovery are. For this patient, the goal was independent walking.
MS H: I had gone through surgery before and I was fine. I just tootled along. So, this time I was surprised at how weak I was and [at] my inability to walk afterwards…At first, I couldn't even get over to the commode by myself…By the time I left the rehab unit, I [could] climb 8 steps and…walk about 100 ft, then sit down and rest, then walk further.
Rehabilitation is helpful whether the patient is treated with radiation, surgery, or both. Critical to the success of rehabilitation efforts is integration of patient and support group and family efforts with those of the multidisciplinary team. In rehabilitation units, paraplegic patients with bowel and bladder incontinence receive instruction in transfers, incentive spirometry, nutrition, bowel and bladder care, and skin care.108 Ambulatory patients receive strength and mobility training. Along with this improved strength, the multilevel fixation achieved by modern spinal instrumentation has made postoperative bracing optional109; it does not lead to a higher spinal fusion rate or improve pain relief.
Observational studies have shown that patients with spinal cord compression who receive rehabilitation have increased satisfaction with life, less depression, and persistent decreases in pain.108,110 In 1 study, average length of inpatient rehabilitation was 27 days; 84% of patients were discharged to home; and mobility, ambulation, self-care, and transfer abilities persisted for at least 3 months after discharge.111
MS H: I had a contractor come and build a ramp in my house while I was gone, and they put a shower in the garage because I couldn't get upstairs. I just made 1 ramp in my house because the living room is sunken, so we put a ramp in for the wheelchair.
We took out the bathroom door downstairs, so I could put the commode in there. When I was in the rehab unit, they arranged for a hospital bed to be delivered to my house, and I arranged for somebody to be there when it was delivered. I just put the hospital bed downstairs, because it's a big room with the television and the kitchen and all that, so I just live down here.
I don't have to make any modifications to my car because my feet are fine. I haven't driven because I have to go to the doctor and get an OK to take this brace off so I can turn and twist. It looks like Joan of Arc armor, that's what I call it. The hospital fitted it for me…I wear it when I do [physical therapy] and stuff. I don't want to drive because I can't turn around until everything is healed in my back.
Oncologists and palliative care clinicians can also help patients and families begin to explore and cope with changes in self-image, independence, roles in the family and community, and living arrangements. Questions to help the clinician understand the patient better include the following:
Help me understand what a typical day at home (work, school, etc) was like for you before the (pain, weakness, numbness) started. What are the things you need to get done? What do you really enjoy doing?
Have you ever needed help to take care of yourself before, or has it happened to anyone close to you? How did you deal with that? Did you see a counselor? Did your clergy or religious community support you?
Do you know anyone who had to use a cane or a wheelchair to get around? How did you feel about that? How do you think it might make you feel?
If you weren't able to walk on your own, what would it take for you to be able to stay at home? Who is there to help during the day and overnight?
For patients with limited prognoses, clinicians should also help the patient and family identify health care proxies and delineate preferences regarding cardiopulmonary resuscitation. Questions to help in doing this include:
Whom do you regularly consult about important issues? Is there one person who really understands what is important to you and how you make your choices about treatments?
If, at sometime in the future, you weren't able to tell us directly what you wanted, should we talk with them? They would be what we call a health care proxy. We would ask them to tell us what they think you would want us to do.
This work is especially important for patients with spinal cord compression due to lung or gastrointestinal cancers (especially those with multiple metastases) because of their short median survival or for any patient who is nonambulatory after surgery or radiation therapy. By refocusing efforts from disease-oriented therapies to creating legacies and bringing closure to their personal relationships, oncology teams can reassure patients and their families that they will not be abandoned. Oncologists can remain the patient's physician in hospice programs, and for patients whose needs exceed those that hospice programs can provide, palliative care teams can help oncology teams provide care and comfort during the final months.