Book traversal links for Evidence from trial or study results: spinal cord compression
This section is based on the 2001 Clinical practice guidelines for the management of advanced breast cancer1 and updated to include results from a randomised trial on decompressive surgery40 and a systematic review by Loblaw et al.41 Results from a retrospective analysis of breast cancer patients by Tancioni et al included in the systematic review are also noted below.111
Symptoms of spinal cord compression
Patients who are known to have bony metastatic disease and their carers should be warned about the possibility of, and educated regarding the early symptoms of spinal cord compression. Patients should be encouraged to notify their doctor of such symptoms as soon as possible. Primary medical carers should also be aware of the risks of spinal cord compression and paraplegia and the importance of prompt action. Symptoms suspicious of spinal cord compression should be investigated in the absence of signs.1
The systematic review by Loblaw et al (2005) identified twelve studies investigating the clinical symptoms of metastatic spinal cord compression from various primary tumours.41 Frequently observed symptoms include back pain, motor weakness, sensory changes and bladder dysfunction.
A retrospective review was included in the Loblaw 2005 systematic review(Talcott et al 1999) which identified six predictive factors for spinal cord compression, including the inability to walk, increased deep tendon reflexes, compression fractures on radiographs of the spine, bone metastases present, bone metastases diagnosed more than one year prior, and age less than 60 years.112
A prospective cohort study (Husband 1998) found that approximately 70% of patients with spinal cord compression experienced loss of neurologic function between the onset of symptoms and the start of treatment.113 The majority of delays were attributed to lack of symptom recognition by the patient and diagnostic delay at the general practitioner or hospital level.
Investigation of suspected spinal cord compression
If spinal cord compression is suspected, whether on symptomatic or clinical grounds, the investigation of choice is MRI scan.114 This is non-invasive and the precise level or levels of cord compression can be ascertained. If this is not available, then CT scan should be used.115 The Loblaw 2005 systematic review identified four studies investigating the accuracy of MRI, reporting sensitivity ranging from 0.44-0.93 and specificity ranging from 0.90-0.98.
Use of corticosteroids
One small RCT identified in the Loblaw 2005 systematic review (Vecht et al 1989) compared high (100mg) to moderate (10mg) initial dose of dexamethasone in patients with complex myelographic obstruction.37 All patients were treated with radiotherapy and maintenance dexamethasone of 16mg/d orally after the initial treatment. At one week, no significant differences were reported between the high and moderate dose groups in pain, ambulation or bladder function.
A second RCT by Sorensen et al (1994) included in the Loblaw 2005 systematic review compared high-dose dexamethasone therapy as an adjunct to radiotherapy (n=27) with no dexamethasone (n=30).38 Immediately after myelography or MRI, patients randomised to dexamethasone treatment received an intravenous bolus of 96mg. The patients were then maintained on a dose of 96mg dexamethasone for 3 days (given orally when possible in four divided doses), and the treatment was then tapered in 10 days. Successful treatment, defined as preservation of gait in ambulatory patients or restoration of gait within 3 months in non-ambulatory patients, was obtained in 81% of the patients treated with dexamethasone compared to 63% of the patients without dexamethasone treatment. In a subgroup analysis of breast cancer patients, a successful treatment result was achieved in 94% of dexamethasone patients compared with 69% of patients without dexamethasone, although difference was not significant.38
Life table analysis demonstrated a higher percentage of patients receiving dexamethasone surviving with gait function during 1 year compared with those not receiving dexamethasone (p=0.046).38 Six months after treatment, 59% of the patients in the dexamethasone group were still ambulatory compared to 33% in the no dexamethasone group (p=0.05). Median survival was 6 months in the two treatment groups. Significant side-effects were reported in three (11%) of the patients receiving glucocorticoids, two of whom discontinued the treatment.38
A case-control study (Heimdel et al 1992) compared high and moderate doses of maintenance corticosteroids in patients treated with radiotherapy for spinal cord compression.39 A statistically significant increase in the number of serious side effects was observed among patients receiving the high dose (4 of 28 patients, 14%), compared with no reports of serious side effects in the moderate dose group (p=0.0284). Serious adverse effects included ulcers with haemorrhage, rectal bleeding and gastrointestinal perforations. The total incidence of side effects was also significantly higher in the high dose group compared with the normal dose group; 8/28 vs. 3/38 respectively, p=0.0429.
Patients presenting with suspected spinal cord compression should be reviewed as early as possible by a spinal surgeon or neurosurgeon with an interest and expertise in spinal problems in consultation with a multidisciplinary team as appropriate.1
A randomised trial assigned patients with spinal cord compression caused by metastatic cancer to either surgery followed by radiotherapy (n=50, breast cancer patients=7) or radiotherapy alone (n=51, breast cancer patients=6).40 Radiotherapy for both groups was given as 30 Gy in 10 fractions. Patients with a displaced spinal cord by an epidural mass, restricted to a single area were eligible for inclusion. Patients were excluded if they had multiple compressive lesions, certain radiosensitive tumours (such as lymphoma) or pre-existing or concomitant neurological problems. Patients were required to have a good general medical status to be acceptable surgical candidates, with an expected survival of at least three months.40 The primary endpoint of the trial was the ability to walk. Secondary endpoints were urinary continence, muscle strength and functional status, the need for corticosteroids and opioid analgesics, and survival time.
Because of demonstrated superiority of surgical treatment, the trial was stopped early by the data safety and monitoring committee.
Significantly more patients in the surgery group (84%) than in the radiotherapy group (57%) were able to walk after treatment (odds ratio 6.2, p=0.001).40 Patients treated with surgery also retained the ability to walk significantly longer than did those with radiotherapy alone (median 122 days vs. 13 days, p=0.003).
Among the subgroup of patients who could walk at study entry, 94% (32 of 34 patients) in the surgery group continued to walk after treatment, compared with 74% (26 of 35 patients) in the radiation group (p=0.024). Patients receiving surgery maintained the ability to walk significantly longer than patients receiving radiotherapy (median 153 days compared to median 54 days, odds ratio 1.82, p=0.024). Among the 16 patients in each group unable to walk at study entry, ten patients (62%) in the surgery group regained the ability to walk, compared with three patients (19%) receiving radiotherapy (p=0.012).
Surgical treatment was significantly associated with maintenance of continence, muscle strength, functional ability and increased survival times. The need for corticosteroids and opioid analgesics was significantly reduced among patients in the surgical group.40
Thirty-day mortality rates were 6% in the surgical arm compared to 14% in the radiation arm (p=0.32). The median hospital stay was 10 days for patients in the surgical and radiotherapy arms (p=0.86).
The authors concluded that decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer.40 The surgical approach should be dictated by the position of the tumour within the vertebra. When surgery is not considered appropriate, radiotherapy should be started immediately.
A retrospective analysis of breast cancer patients with metastatic epidural spinal cord compression identified 23 patients who underwent either minimal resection (n=5), curettage leaving microscopic residual tumour (n=18) or total resection (n=3) followed by radiotherapy within 30 days. Median survival of 36 months was reported. The median duration of clinical remission was 26 months. Complete or partial clinical remission of pain was obtained in all cases, and all 17 patients presenting with neurologic deficit experienced compete recovery.111
Three prospective studies, two case-control studies, one case series and three retrospective reviews were identified in the Loblaw 2005 systematic review comparing various doses of radiotherapy to treat metastatic spinal cord compression.41 Doses included:
- 30 Gy in 10 fractions
- 37.5 Gy in 15 fractions
- 40 Gy in 20 fractions
- 28 Gy in 7 fractions
- 15 Gy in 3 fractions / 15 Gy in 5 fractions
- 8 Gy twice
No regimens demonstrated higher rates of ambulation compared with another.
As noted in the Surgery section above, a randomised controlled trial (Patchell 2005) comparing surgery followed by radiotherapy with radiotherapy alone was stopped early due to proven superiority of the surgical treatment. Ten patients in the radiation group (20%) experienced substantial decline in motor strength during radiotherapy and crossed over to receive surgery. None of these patients could walk at the time of surgery; three (30%) regained the ability to walk.