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National Collaborating Centre for Cancer (UK). Metastatic Spinal Cord Compression: Diagnosis and Management of Patients at Risk of or with Metastatic Spinal Cord Compression. Cardiff (UK): National Collaborating Centre for Cancer (UK); 2008 Nov. (NICE Clinical Guidelines, No. 75.)

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Metastatic Spinal Cord Compression: Diagnosis and Management of Patients at Risk of or with Metastatic Spinal Cord Compression.

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1Epidemiology

1.1. Introduction

Metastatic spinal cord compression (MSCC) is a well recognised complication of cancer and is usually an oncological emergency. MSCC was first described by Spiller in 1925 as progressive paraplegia in cancer patients (Loblaw et al. 2003).

Metastases to the spinal column occur in 3–5% of all patients with cancer (most commonly those with breast cancer, prostate cancer and lung cancer, in whom the incidence may be as high as 19%) and may cause pain, vertebral collapse and MSCC.

Patients with breast, lung and prostate cancer account for more than 50% of MSCC cases but it can be caused by any solid tumour. Patients who present with widespread malignancy and those with known spinal metastases are also at higher risk. The risk of MSCC is also proportionally related to the duration of disease and therefore, as cancer survival times increase, so too might the incidence of MSCC.

MSCC occurs when there is pathological vertebral body collapse or direct tumour growth causing compression of the spinal cord or cauda equina. Irreversible neurological damage ensues with resulting paraplegia (Levack et al. 2002). Early diagnosis and treatment is essential to prevent neurological damage and to achieve this, early recognition and reporting of symptoms, simple and rapid referral pathways, urgent and appropriate investigations and prompt treatment are needed.

Therefore it is important that the patient and all health care professionals are aware of the early symptoms and signs of MSCC (Loblaw et al. 2003, Levack et al. 2002, Husband 1998, Bucholtz 1999). Unfortunately, the symptoms and signs that are usually taught are those of established MSCC such as weakness of the limbs, bladder and bowel dysfunction and sensory loss.

There is a significant association between the ability to walk at the time of diagnosis and the ability to walk following treatment (Brown et al. 1999, Hacking et al. 1993, Huddart et al. 1997, Kim et al. 1990). Furthermore, data from the Clinical Resource Audit Group (CRAG audit) (Levack et al. 2001), suggest that the ability to walk at the time of diagnosis is a statistically significant predictor of outcome in terms of survival.

Once paraplegia develops it is usually irreversible. and can affect the quality of life of both the patient and their carers. These patients often need 24 hour nursing care either in hospital or in the community setting, which has major resource implications on the National Health Service (NHS).

The key investigation for the diagnosis of MSCC is magnetic resonance imaging (MRI) of the whole spine (Levack et al. 2001, Cook et al. 1998). Once a diagnosis of MSCC has been made, the treatment goals include pain relief, restoration of neurological status, prevention of further neurological damage and stabilisation of the spine (Husband 1998, Held & Peahota 1993, Royal College of Radiologists 2006).

When deciding the most appropriate treatment option for a patient it is important to consider quality of life (QOL) issues. Although there have been many studies that have assessed QOL in patients with advanced cancer, few have been on patients with MSCC (Levack et al. 2001).

1.2. Incidence

The true incidence of MSCC is unknown, post mortem evidence indicates that it is present in 5–10% of patients with advanced cancer. Levack et al. (2001) have also estimated similar figures in terms of incidence. In their report of a population based study from Ontario Canada, Loblaw et al. (2003) described a cumulative probability of experiencing at least one episode of MSCC in the 5 years preceding death from cancer of 2.5% overall with a 40-fold variation in the cumulative incidence of MSCC among different types of cancer. The authors acknowledged that they may have underestimated the true incidence by at least 15%, as the detection rate depended on admission to hospital, correct diagnosis, and entry into coding systems (Loblaw et al. 2003). One of the main reasons for the uncertain incidence of MSCC in the UK is the lack of a recognised coding system for the diagnosis. It is likely that the incidence of MSCC will increase in the future with improving cancer treatments resulting in better survival and outcomes.

The median age at time of MSCC diagnosis is 65 years (Loblaw et al. 2003, Levack et al. 2001). Data from the Levack et al. audit (2001) suggest that 77% of patients diagnosed with MSCC had an established diagnosis of cancer whereas 23% presented with MSCC as the first presentation of malignancy.

1.3. Aetiology and pathophysiology

Loblaw et al. (2003) define MSCC as compression of the dural sac and its contents, namely the spinal cord and cauda equina, by an extradural mass. Lung, breast and prostate cancers are the commonest malignancies causing MSCC and account for over 50% of cases (Loblaw et al. 2003, Levack et al. 2001). In 7% of patients the site of primary tumour may remain unidentified (Levack et al. 2002, Levack et al. 2001).

Three mechanisms are responsible for MSCC, the commonest being haematogenous spread to the vertebral spine causing collapse and compression, accounting for over 85% of cases (Bucholtz 1999, Levack et al. 2001). Less commonly it occurs secondary to direct tumour extension into the vertebral column or by direct deposition of tumour cells (Bucholtz 1999).

The cause of damage to the spinal cord from compression is complex and multifactorial. Direct compression results in oedema, venous congestion and demyelination. If the compression is gradual and of recent onset with some preservation of neurological function, the effects are often reversible. With prolonged compression, vascular injury ensues causing infarction of the spinal cord. After this type of injury any meaningful recovery is unlikely (Patchell et al. 2005). Paradoxically, slow onset compression (with an accompanying gradual neurological deficit) permits a degree of cord adaptation and usually predicts a better outcome than sudden onset compression and neurological loss.

1.4. Clinical symptoms and signs

Back pain is the most frequent first symptom occurring in 95% of patients for prolonged periods and usually precedes signs related to MSCC (Levack et al. 2001, Portenoy 1997, Byrne 1992, Quinn & DeAngelis 2000). The pain is described either as localised,spinal pain or neurogenic, radicular pain. Localised spinal pain is defined as pain in and around the spinal column area in distinction to neurogenic radicular pain, which is spinal cord or nerve root pain affecting one or both sides of the body (Levack et al. 2001). In the Levack et al. audit (2001) 37% of patients with MSCC had neurogenic radicular pain, 15% had localised, spinal pain on its own and 47% had localised spinal pain and neurogenic, radicular pain. The median pain intensity was 8 on a scale of 0 to 10 with 0 being ‘no pain’ and 10 ‘the worst imaginable pain’.

Weakness of the limbs is the second most common symptom of cord compression. Eighty five percent of patients in the Levack et al. (2001) audit experienced weakness and in the majority pain preceded weakness. Only 18% of patients were able to walk without help at the time of diagnosis of MSCC (Levack et al. 2001).

Sensory symptoms are also common and include paraesthesia, decreased sensation and numbness of toes and fingers which may extend to the level of cord compression (Held & Peahota 1993). Fifty two percent of patients had a clinical sensory level but this varied significantly in relation to the true compressive lesion (Levack et al. 2001). Autonomic dysfunction is a late consequence of MSCC and rarely occurs without symptoms and signs. This may present as impotence or bladder and bowel dysfunction presenting as urinary retention, incontinence or constipation (Bucholtz 1999). Constipation was the commonest bowel symptom and occurred in 67% of patients (Levack et al. 2001).

Over two thirds of cases of MSCC occur in the thoracic spine and between 4 and 7% occur in the cervical cord (Loblaw et al. 2003, Levack et al. 2002, Cook et al. 1998). Seventeen percent of patients have two or more levels of cord compression (Levack et al. 2002).

1.5. Survival/mortality

Median survival following a diagnosis of MSCC is reported as being around 2 to 3 months (Loblaw et al. 2003, Levack et al. 2001) with 17% patients alive at one year and 10% patients at 18 months (Levack et al. 2001). The median survival of untreated patients from a diagnosis of MSCC is one month (Loblaw et al. 2003) but this may reflect selection bias for treatment. Several studies have reported survival to be significantly associated with the ability to walk at time of diagnosis. The Levack et al. audit (2001) found primary tumour site and ability to walk at diagnosis of MSCC as independent predictors of survival.

Loblaw et al. (2003) reported large differences in survival following MSCC in different disease groups. Longest survival was reported in patients with haematological malignancies (lymphoma, leukaemia and multiple myeloma) and prostate cancer whereas lung cancer patients had the shortest survival. Similar results were reported by Levack et al. (2001) with 66% survival at 3 months for patients with haematological malignancies and 22% survival at 3 months in patients with lung cancer.

Surgically treated patients had significantly better survival at one year (57.4% vs 13.3%) than patients not surgically treated (Levack et al. 2001). This is likely to be a result of patient selection rather than a direct relationship.

1.6. Service provision

To inform the development of this guideline a questionnaire survey of incidence, availability of resources and variation in clinical practice in relation to MSCC in England and Wales was carried out. The aim of this survey was to determine differences in service provision, specifically access to:

  • Spinal surgical services
  • Oncological services
  • Other services.

A questionnaire was sent to all cancer centres in England and Wales. In addition, questionnaires were also sent to all known orthopaedic and neurosurgical spinal surgery units, palliative care units and rehabilitation units in England and Wales. Copies of these questionnaires will be reproduced in the full needs assesment which will form part of the evidence review. As part of the questionnaire departmental studies or audits were also requested. In total, replies were received from 27/57 (47%) cancer centres, 21/61 (34%) spinal surgery units, 116/353 (33%) palliative care departments and 7/10 (70%) specialist rehabilitation units.

Incidence

The average catchment area for cancer centres is 1.2 million people (median 1 million, range 0.3 to 3 million). On average 80 MSCC cases are seen per year in each centre (median 55, range 10 to 250). Prostate cancer was the commonest primary tumour site in 15 (55%) units.

The mean catchment area for spinal surgery units is 2.4 million people (median 2.2 million range 1.2 to 4.2 million). On average 56 MSCC cases are seen per year in each unit (median 50, range 5 to 150). Breast cancer was the commonest primary tumour site in 13 (62%) units. Prostate cancer was not reported as the commonest primary site in any unit.

The mean catchment area for a palliative care department is 0.42 million people (median 0.35 million, range 0.1 to 2.6 million). On average 16 MSCC cases are seen per year in each department (median 12, range 3 to 150). Prostate cancer was the commonest primary tumour site in 45 (39%) units.

Specialist spinal rehabilitation units have large catchment areas, with an average of 6.4 million people (median 6 million, range 3 to 10 million). The mean number of MSCC patients seen in the 3 units accepting these patients is 4 per year.

MRI

Cancer centres

Of those centres which responded to the questionnaire 23/27 (85%) have a written policy on the investigation of suspected MSCC. Before a confirmed diagnosis 18 (67%) centres routinely keep patients lying flat. Interestingly 8 centres (35%) with a written policy do not recommend patients lie flat before a diagnosis is made.

In all the 27 centres who responded, MRI is available during weekday working hours and 23 (85%) reported that it is ‘easy’ or ‘very easy’ to access. A weekday out-of-hours service is available in 16 (59%) centres. All other centres wait until the following morning. An on-site weekend service is available in 16 (59%) centres. Of the remainder, 6 (22%) refer patients to another hospital for scanning over the weekend, and 5 (19%) wait up to 48 hours until Monday morning. In total 19 centres (70%) are able to organise an MRI scan within 24 hours of the medical decision to request one. One centre did however report a delay of up to 72 hours; this centre did not provide an out-of-hours or weekend service. In 23 centres (85%), the whole spine is scanned, in 3 (11%) a limited scan is performed. One centre did not know the extent of scanning.

Spinal surgery units

Of those units which responded to the questionnaire 10/21 (48%) have a written policy on the investigation of suspected MSCC. Before a confirmed diagnosis, 13 units (62%) routinely keep patients lying flat. Eight of the 10 units (80%) with a written policy recommend that patients lie flat before a diagnosis is made, which is higher than in cancer centres. In all 21 units who responded to the questionnaire MRI scanning was available on-site and all patients with suspected MSCC had an MRI scan. In 19 units (90%), MRI is available outside of normal working hours. On a weekday, the remaining 2 units (10%) wait until the following morning, and over the weekend patients are referred to another hospital for scanning. Twelve units (57%) are able to organise an MRI scan within 24 hours of the medical decision to request one. Three units (14%) reported a delay of up to 72 hours despite there being MRI available on site and outside working hours. In 19/21 centres (90%), the whole spine is scanned, in 2 (10%) a limited scan is performed.

Palliative care departments

In 99/116 departments (85%) which responded to the questionnaire more than 75% of patients have an MRI scan to confirm the diagnosis. Only 32 units (28%) routinely lie patients flat 17 (15%) of respondents were unsure); this is much lower than in Cancer Centres or Spinal Surgery Units. Fifty three units (46%) have a written policy on the management of MSCC (8 (7%) of respondents were unsure). On-site MRI is available in 72 units (62%) (24 of 116 departments or (21%) of respondents were unsure). In 110 units (95%) MRI is only available during normal working hours. Access during working hours was deemed as ‘very easy’ or ‘easy’ in 96/116 units (83%). The whole spine is scanned in 90 units (78%).

Surgical services

Cancer centres

In total, 19 centres (70%) report it is ‘easy’ or ‘very easy’ to contact the surgical team. On site surgical review is available in 10 centres (37%). The average distance to a spinal unit is 10 miles (range 0 to 60 miles). Only a minority of patients are referred for review; in 18 (centres 67%) less than 25% are assessed by the surgical team. Of those patients reviewed, 14 of centres (52%) report that over 50% proceed to surgery.

Spinal surgery units

Sixteen units (76%) do not have a defined policy for selecting patients for surgery. Five units (24%) use the Tokuhashi score. In 11 units (52%) over 75% of the patients referred for surgical review are not operated on. Only 4 units (19%) operated on more than half of the patients seen which is much lower than the surgical rates reported by cancer centres. Surgery is carried out within 72 hours of the decision to operate in all but one centre. In cancer centres and palliative care units prostate cancer seems to be the commonest primary site. However, no spinal unit reported prostate cancer as the commonest malignancy. Breast cancer was the commonest primary tumour site in 13 units (62%). This suggests that either proportionally more breast cancer patients are referred or accepted for surgical review than other primary sites.

Palliative care departments

Surgery is an uncommon treatment for patients, with 104 units (90%) reporting that 25% or less are operated on (9 or 8% of respondents were unsure). Sixty two centres (53%) report it is ‘easy’ or ‘very easy’ to contact the surgical team. The average distance to a Spinal Surgery Unit is 14.5 miles (range 0 to 100 miles).

Oncology services

Cancer centres

Most centres (23 or 85%) reported that patients with a diagnosis of MSCC are seen within 24 hours by an oncologist. No centre reported a wait of more than 48 hours. Patients are usually treated with radiotherapy; more than 75% of patients in 25 centres (93%) and 50–75% of patients in 2 centres (7%). Eleven centres (41%) will treat some patients without radiological confirmation of MSCC. The decision to treat without a radiological diagnosis may depend on the availability of MRI; seven centres (26%) treating without MRI wait more than 24 hours for a scan compared to only one (6%) of the remaining centres. It was not asked whether these patients go on to have MRI scans once the radiotherapy has begun. Radiotherapy is started within 24 hours of the diagnostic MRI scan in 25 centres (93%). No centre reported a delay of more than 48 hours in starting radiotherapy. Treatment can start on Saturday in 26 centres (96%) and on Sunday in 22 centres (85%). Various radiotherapy dose regimens are used, but by far the commonest is 20Gy in 5 fractions, which is the schedule of choice in 23 centres (85%). A written policy on steroid usage exists in 20 centres (74%). All centres use dexamethasone and 21 centres (78%) recommend a total daily dose of 16mg.

Spinal surgery units

Thirteen centres (62%) routinely refer more than 75% of patients for post-operative radiotherapy while 8 (38%) refer 25–50%. Access to radiotherapy is reported as ‘very easy’ or ‘easy’ in 20 units (95%). A written policy on steroid usage exists in 9 units (43%). Somewhat surprisingly, two units (10%) do not routinely use steroids. All other 19 units use dexamethasone and 15 centres (79%) recommend a total daily dose of 16mg.

Palliative care departments

Access to oncology services is reported as ‘very easy’ or ‘easy’ in 84 units (72%). However, 29 departments (25%) report access to oncology services as ‘difficult’. Despite this, 90 departments (78%) have oncology review within 48 hours (6 or 5% of respondents were unsure). Radiotherapy is the commonest treatment for patients with MSCC, with 106 centres (91%) reporting over 50% of patients being treated in this way (4 or 3% of respondents were unsure). Twenty five departments (22%) reported that some patients are treated without prior MRI scanning. Waiting times for radiotherapy are generally good; in 63 units (54%) patients wait less than 24 hours before starting radiotherapy. In only 3 departments (2%) is the wait more than 48 hours (21 or 18% of respondents were unsure). Seventy three departments (63%) reported that radiotherapy can be started on a Saturday (28 or 24% of respondents were unsure). Encouragingly, only 15 departments (13%) reported that radiotherapy cannot start on a Saturday, which is similar to the proportion of cancer centres unable to provide this service. This suggests that patients in palliative care units may get similar access to radiotherapy as those in cancer centres. In total, 56 (48%) have a written policy on steroid usage (30 or 26% of respondents were unsure). All 116 units use dexamethasone and 110 centres (95%) recommend a total daily dose of 16mg.

Other services

Cancer centres

Access to specialist physiotherapy is variable with only 13 centres (48%) providing this service (6 or 22% of respondents were unsure). Daily physiotherapy is available in 17 centres (63%) and 8 centres (30%) have a written policy on mobilisation. Occupational therapy is available in 25 centres (93%) (2 respondents were unsure). Only 8 centres (30%) have a continence adviser (13 or 48% of respondents were unsure). Referral to specialist rehabilitation services is available to patients in 17 centres (63%) (5 or 19% of respondents were unsure). An average of 5 patients per year (range 1 to 10) were referred for specialist rehabilitation in the 9 centres (30%) that provided this information.

Spinal surgery units

Access to specialist physiotherapy is available in 10 units (48%) (2 or 10% of respondents were unsure). Daily physiotherapy is available in 17 units (81%) and 5 units (24%) have a written policy on mobilisation (2 or 40% of respondents were unsure). Occupational therapy is available in 19 units (90%) (1 or 5% of respondents were unsure). Fifteen units (71%) have a continence adviser (3 or 14% of respondents were unsure). Referral to specialist rehabilitation services is available to patients in 16 units (76%) (1 or 5% of respondents were unsure). An average of 5 patients per year (range 2 to 10) were referred for specialist rehabilitation in the 10 centres (48%) that provided this information.

Palliative care departments

Access to specialist physiotherapy is available in 65 departments (56%) (15 or 13% of respondents were unsure). Sixty nine departments (59%) reported that patients are assessed by a physiotherapist within 48 hours of referral. Fourteen departments reported waiting more than 72 hours for physiotherapy review (22 or 19% of respondents were unsure). One department has no inpatient physiotherapy service. It is important to note that following diagnosis it may not be appropriate or necessary for a patient to be reviewed immediately by a physiotherapist; pain relief may need to be optimised and a policy of strict bed rest during radiotherapy is often applied and no mobilisation is attempted. Only 10 departments (9%) have a written mobilisation policy (43/116 or 37% of respondents were unsure).

Specialist spinal rehabilitation units

Only 3 units (43%) accept MSCC patients and these units only see on average four such patients per year. Specialist rehabilitation services are available to patients in at least 17 (63%) cancer centres and 16 (76%) spinal units with an average of five patients per year referred from each cancer centre and spinal unit. This strongly suggests that either our list of rehabilitation units is incomplete or the definition of a rehabilitation unit is not clear. The small number of units accepting MSCC patients makes any meaningful data interpretation very difficult. Surprisingly, two (67%) units reported no access to specialist physiotherapy (One (33%) respondent unsure). Daily physiotherapy is available in all 3 units. Waiting times for transfer are 4 weeks in two (67%) units and ‘variable’ in the other. All three units have access to specialist occupational therapy, and 2/3 (67%) units have a continence adviser. All three units have a community rehabilitation team.

1.7. Conclusions

The needs assessment has highlighted several important findings relating to current service provision for patients at risk of or diagnosed with MSCC. Existing epidemiological data in the UK is poor (e.g. incidence, survival, mortality) with no nationally coordinated data collection. In addition there is a recognised lack of an appropriate system for coding a diagnosis of MSCC.

Data derived from the questionnaire survey of cancer centres, spinal surgery units and palliative care departments indicated a range in service provision for this group of patients including availability and access to out of hours MRI, defined policies for patient selection for surgery and access to specialist physiotherapy and rehabilitation services. It is possible that responder bias resulted in proportionally more replies from centres where a high level of care is provided or where there is a special interest in MSCC. The possibility that centres with poor service provision are underrepresented in this audit cannot be excluded. Therefore this data may portray the management of MSCC more favourably than is the reality in some centres. This is reflected in individual patient experiences which are discussed in more detail in Chapter 3 of this guideline.

All these data were presented to the GDG during guideline development to help focus on some of the key priority areas and data from the needs assessment are included as part of the evidence review where appropriate. The full needs assessment (including all the data from the questionnaires) will form part of the final evidence review which will accompany this guideline.

The NCC-C and GDG would like to thank all those health care professionals who completed and returned their questionnaires as part of this needs assessment exercise.

References

  • Brown PD, Stafford SL, Schild SE. Metastatic spinal cord compression in patients with colorectal cancer. Journal of Neuro-Oncology. 1999;44:175–180. [PubMed: 10619502]
  • Bucholtz JD. Metastatic epidural spinal cord compression. Seminars in Oncology Nursing. 1999;15(3):150–159. [PubMed: 10461699]
  • Byrne TN. Spinal cord compression from epidural metastases. New England Journal of Medicine. 1992;327:614–619. [PubMed: 1296600]
  • Cook AM, Lau TN, Tomlinson MJ. Magnetic Resonance Imaging of the whole spine in suspected spinal cord compression: Impact on management. Clinical Oncology. 1998;10:39–43. [PubMed: 9543614]
  • Hacking H, Van As H, Lankhorst G. Factors related to the outcome of inpatient rehabilitation in patients with neoplastic epidural spinal cord compression. Paraplegia. 1993;31:367–374. [PubMed: 8336999]
  • Held JL, Peahota A. Nursing care of the patient with spinal cord compression. Oncology Nursing Forum. 1993;20(10):1507–1516. [PubMed: 8278278]
  • Huddart R, Rajan B, law M. Spinal cord compression in prostate cancer: Treatment outcome and prognostic factors. Radiotherapy Oncology. 1997;44:229–236. [PubMed: 9380821]
  • Husband DJ. Malignant spinal cord compression: prospective study of delays in referral and treatment. BMJ. 1998;317:18–21. [PMC free article: PMC28596] [PubMed: 9651261]
  • Kim R, Spencer S, Meredith R. Extradural spinal cord compression: analysis of factors determining functional prognosis-prospective study. Radiology. 1990;176:279–282. [PubMed: 2353102]
  • Levack P, Graham J, Collie D. A prospective audit of the diagnosis, management and outcome of malignant spinal cord compression. 2001. Clinical Resource and Audit Group Levack et al. 2001 97/08.
  • Levack P, Graham J, Collie D. Don’t wait for a sensory level-Listen to the symptoms: a Prospective audit of the delays in diagnosis of malignant cord compression. Clinical Oncology. 2002;14:472–480. [PubMed: 12512970]
  • Loblaw, Laperriere NJ, Mackillop WJ. A population-based study of malignant spinal cord compression in Ontario. Clinical oncology. 2003;15(4):211–217. [PubMed: 12846501]
  • Patchell RA, Tibbs PA, Regine WF. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. The Lancet. 2005;366:643–648. [PubMed: 16112300]
  • Portenoy RK. Chronic nociceptive pain syndromes: Cancer pain. In: North RB, Levy RM, editors. Neurosurgical Management of Pain. New York, NY: Springer-Verlag; 1997. pp. 62–74.
  • Quinn JA, DeAngelis neurological emergencies in the cancer patient. Seminars in Oncology. 2000;27(3):311–321. [PubMed: 10864219]
  • Royal College of Radiologists. Board of Faculty of Clinical Oncology. Spinal cord compression, Radiotherapy Dose-Fractionation. 4.17. 2006. p. 70.
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