Charles G. Fisher, M.D., FRCSC
Vancouver, BC

Introduction

Spinal metastasis is a frequent oncologic problem which occurs in more than 1/3 of patients with malignant tumours.17,20 Approximately 60% arise from myelomas and carcinomas of the breast, prostate, kidney and lung. Although the presence of metastases signifies incurable disease, the majority of these patients have a relatively favorable life expectancy.4,14 As these cancer patients live longer secondary to improved medical, surgical and adjuvant therapies, spinal metastasis pose a greater threat to their independence and survival.

The spine is similar to the appendicular skeleton in that it provides a load bearing function but differs in that it serves to protect the spinal cord and other neural elements. Spine tumours therefore can not only bring about severe pain secondary to collapse or loss of integrity of the supporting structures of the spine, but also cause partial or complete paralysis. These factors can obviously have significant effects on the patient's pain, function, and thus quality-of-life. Both the potential neurologic morbidity and/or spinal instability present a significant challenge to the oncologist and/or spine surgeon when trying to manage these patients.

Cancer patients are complex with a multitude of factors affecting local morbidity and survival. These include: tumour type and histology; the region of the spine involved; magnitude of neurologic deficit; magnitude of instability; metastasis to other organs or other regions of the spine; and, the general well being of the patient.19 Spinal instability, defined as the inability of the spine to withstand normal physiologic forces resulting in pain or deformity, is often a very difficult concept to understand and diagnose. There is a continuous spectrum of tumour involvement in the spine; small deposits providing no threat to the structural integrity of the vertebrae to complete destruction of the vertebrae causing severe pain, deformity plus or minus neurologic injury. The extremes of this continuum are relatively straightforward to diagnose and treat, but there is a large portion in the middle where the degree of instability, potential or present neurologic deficit, and underlying cause of the pain is difficult to diagnose and treat. It is this segment of the spinal metastases population that poses the greatest challenge to both the oncologist and surgeon.

Clinical Assessment

The diagnosis of spinal metastatic disease involves a thorough history and physical examination. From the clinical evaluation, further investigations to determine the local and systemic spread of the malignancy and facilitate treatment can be carried out. It is important when considering treatment that the natural history of each individual metastatic process be known. Thus, in developing a holistic view of the patient, their current disability and the systemic spread of the malignancy, we can plan management that is optimal for the patient's quality-of-life.

The chief complaint in the majority of patients is pain. In spine metastases, the pain is usually nonmechanical; however, if the pain is mechanical in nature, this suggests an unstability. There may be a history of neurological symptoms and these can be sensory, motor or autonomic in nature. Past history of the patient looking for any clues as to the etiology of the metastatic process is important. The general disability of the patient from a functional point-of-view and co-existing major organ involvement that limits the patient in a day-to-day fashion is also relevant.

Physical examination must be thorough. Inspection and palpation of the spine for deformity and/or tenderness, and a detailed neurologic exam, is essential. A general exam to assess organ involvement and impairment should be done.

Investigations

Radiographs of the spine in a patient with no previous history of malignancy are helpful from a diagnostic perspective. In the patient with a lytic lesion over the age 40, the diagnosis is most likely to be a metastatic process. The differential diagnosis, however, must remain broad, and includes primary bone tumours, infections, and metabolic processes. In the patient with a known malignancy, the utility of the x-ray shifts from diagnostic to that of the assessment of the mechanical stability of the spine. Fundamental radiographic features such as deformity, collapse and bony involvement must be recognized to direct further investigations. The aim of these further investigations is three-fold. Firstly, in the patient with no known malignancy, to help make a pathologic diagnosis. Secondly, to accurately determine the local and systemic spread of the disease. Finally, to be able to form a rational treatment plan.

Blood work provides a baseline of patient status and can be diagnostic in tumours such as multiple myeloma. Complete blood count, electrolytes, protein, albumin and serum calcium are essential in getting an overview of the patient's general status and help to warn of any impending metabolic crises. Serologic markers for specific tumours sometimes can be helpful from a diagnostic standpoint and to monitor efficacy of treatment.

Imaging can be addressed from a local and system or staging perspective. A chest x-ray and chest CT are very useful in determining pulmonary involvement. A bone scan is sensitive and inexpensive in determining osseous spread, but is not specific. There are false negatives with this imaging modality, for example multiple myeloma, but it is very useful when focusing attention to a specific site that may be more accessible for biopsy purposes in the patient with unknown malignancy.

The CT scan is used to determine the local bony destruction of the spinal metastases and reasonably defines the local extent of the lesion. It may also help with some features of the tumour, for example calcification and ossification within the tumour mass which may provide clues to cellular biology or aid in the differential diagnosis.

Magnetic resonance imaging is an essential tool for the assessment of spinal malignancy. It is a longitudinal study that clearly delineates the neurologic structures and the magnitude of compromise secondary to extradural compression. The MRI can also identify lesions at other levels of the vertebral column. The MRI provides significant reliability in differentiating tumour from a pathologic fracture secondary to osteoporosis.3

Finally, angiography can be a vital component of the investigational armamentarium. In anatomic and surgical circumstances where the blood supply of the spinal cord is threatened, it is encumbant upon the surgeon to have knowledge of the spinal cord blood supply so as to not compromise this through inappropriate surgical intervention. Furthermore, angiography and embolization as an initial step in the surgical management of highly vascular tumours, such as renal cell carcinomas, probably result in reduced peri and postoperative morbidity.

In the patient with no history of malignancy or unknown primary, the disease process must be confirmed. Biopsy becomes part of the investigation, but it is important that a full work-up as described above has been performed prior to the biopsy.

Biopsy techniques can either be closed or open. Closed is usually by fine needle aspiration or core biopsy. Open technique is either by incisional or excisional biopsy. The general principle is to biopsy the most accessible lesion unless there is risk of increasing patient morbidity. The pathological resources available at your institution determine the type of biopsy that is performed. For example, it is of no use performing a fine needle aspiration if there is no one skilled at this cytological diagnosis. It is extremely important that there is an open line of communication between the pathologist and the person performing the diagnosis to ensure that adequate and representative tissue is obtained. In patients with known malignancy the biopsy is, for the most part, confirmatory and is often done at the time of definitive surgical management. The site of the spinal lesion influences the type of biopsy. In the cervical spine it is common to perform an excision biopsy. Frozen section should be undertaken at the time to confirm the diagnosis and the necessity for further tissue. In the thoracic and lumbar spine, closed techniques are more often used. In situations where the diagnosis is unclear and a primary malignancy of the spinal column is high in the differential, then careful planning of the biopsy approach by the potential treating surgeon must be made in order not to jeopardize potential cure.

Armed with complete investigative information and consideration of the patient's disability, treatment planning can now be undertaken. Tumour factors, patient factors, status of the patient's neurologic deficit, the stability of the vertebral column, and the availability of resources are all important considerations in individualizing the treatment plan of each patient. Treatment decisions based on tumour factors will be influenced by the biology of the tumour and the local and systemic extent of the disease. Patient factors that will have an influence are the general status of the patient, neurologic deficit, stability of the vertebral column, and the goals and expectations of the patient. The institution's resources with respect to imaging, surgery, postoperative care and the oncological and rehabilitative facilities will have an influence on the long-term management of the patient.

Criteria for Surgical Decision-Making

Tumour biology has been shown to affect survival. Patients who have vertebral metastases from the colon or lung have much shorter life expectancy than those from the breast or kidney. The extent of disease is also important with multi-organ involvement implying limited life expectancy and multiple level spinal disease possibly negating surgical intervention. Neurologic impairment is also a factor influencing outcome with total paralysis having a much shorter life expectancy than those with incomplete or no neurologic deficit. This influence is irrespective of other factors, for example general status of the patient. Although many schemes have been put forward to try and determine which patients are amenable to surgical intervention, probably that of Tokuhashi is the most practical and validated. Six parameters (general condition, number of extra spinal bony metastases, number of metastases in the vertebral body, metastasis to major organs, neurologic deficit, and primary site of the cancer) are used to predict survival and indicate the appropriate operative procedure spanning through no surgery, limited palliative operation to aggressive excisional surgery and stabilization for those patients expected to live more than one year.19

The other essential element in the planning of treatment for the patient with metastases is to assess the stability of the vertebral column. Originally, surgeons extrapolated from trauma and utilized the three-column assessment. This has been expanded by further splitting the columns into two separate areas.10 While this provides a simplistic approach, it has not been shown to be reliable. Probably the most valid and reliable approach is based on a study by Taneichi.18 This study looks at the impending collapse with metastatic disease of the vertebral column and has shown that factors that determine collapse are different for the thoracic and lumbar spine. In the thoracic spine, destruction of the costovertebral joint is the most important factor in determining stability. Pedicle destruction is important in both the thoracic and lumbar spine, but vertebral body destruction is most relevant only in the lumbar spine. Using a relatively simple scoring system addressing these factors, a reliable method for determining impending collapse within a set time is proposed. The study needs further validation.

Management

In general, the indications for treatment of metastatic disease of the spine are pain, neurologic loss or impending neurologic loss, and instability either present or imminent. The mainstays of treatment for metastatic disease of the spine have been radiation, surgery or both. Chemotherapy, endocrine therapy and steroids have been valuable adjuncts, but are uncommonly the definitive treatment.

Steroids are classically used for neurologic compromise, but are also used in the ongoing treatment of tumours such as myeloma and lymphoma. The classic steroid treatment has used Decadron as an anchylotic agent and to diminish vasogenic oedema. With these two effects, it is often used in the acute scenario where there is progressive neurologic deficit and moderate to severe pain. Steroids often arrest or reverse neurologic deficit, but the effect dissipates with time and can be relied upon usually for only up to 48 hours. There is some controversy surrounding the initial dose that can range from 10 to 100 mg followed by 4 to 6 mg qid. The other common emergency problem is hypercalcemia and well known therapeutic regimes exist utilizing steroids, diuretics and IV hydration.

Due to the burden of patient care falling on the oncologist, the vast majority of these patients receive radiation treatment. Most patients respond well to radiation therapy with respect to pain and sometimes neural compression, especially when the tumour is highly radiosensitive.5,9,12,13,16 Various magnitudes of pain relief occur in 40-70% of patients. Clinical response usually occurs in 3 to 6 weeks.5,8,16 Where the results are less predictable for radiation is in the large group of patients who have clinically and radiographically significant lesions that may be compromising stability. In this patient group, other forms of treatment may be more effective, yet oncologists are often not aware of the potential benefits of surgical intervention.

In the remote past, surgical treatment for spine metastasis provided poor results.2 These results were based on a laminectomy for decompression, which today is absolutely contraindicated in this patient population. With the evolution of spine surgery as a subspecialty, better surgical exposures and dramatically improved spinal instrumentation systems, the indications for surgery in metastatic disease of the spine have broadened and are presently under-utilized due to the lack of cross pollonization amongst the specialists treating oncologic disease.4 With cancer patients living longer, not only spinal metastasis but recurrence of spinal tumours is an important consideration in the management of these patients. Although local recurrence can occur in both patients treated with radiation and surgery, a retrospective study in breast cancer patients has shown women treated with combination radiotherapy/surgery had speedier resolution of symptoms, longer symptom free survival (39 weeks versus 11 weeks) than for patients treated with radiotherapy alone.15 Retrospective studies show surgical treatment of metastatic disease in the spine to be superior to radiation in both neurologic recovery and pain relief.11,14 Neurologic improvement has ranged from 73% to 82% and overall satisfactory outcome from 73% to 89%.11 It is indeed the magnitude of the pain relief that is quite striking, with complete relief and no analgesics occurring in 69% to 94% versus 15% to 40% in patients treated with radiation.2,4,5,14,17

Surgery has the additional advantage of providing immediate functional, physiologic stability. This subsequently enables patients to ambulate immediately, thereby reducing morbidity, decreasing analgesic use, and shortening hospital stay. This provides not only medical, but psychologic benefits to the patient and allows for earlier integration back into their home environment.

Surgical treatment of spinal metastases encompasses three basic principles: 1) decompression, 2) stabilization and 3) realignment. Decompression can be obtained by direct or indirect methods. Direct decompression is removal of the offending bony or soft tissue compressing neural elements. Indirect decompression is obtained by restoring alignment of the spine to relieve bony compression of the neural elements.

Guidelines previously discussed, along with anatomical location and extent of tumour usually dictate one of four operative procedures: anterior vertebrectomy with strut graft and instrumentation; posterior instrumentation with or without decompression; combined anterior and posterior decompression and stabilization; or posterior lateral vertebrectomy with posteriorly placed anterior strut graft and posterior instrumentation. Although these procedures can be technically demanding and resource intensive from an anaesthetic and postoperative care perspective, the critical factor is probably more in the surgical decision-making than the technique itself. Any four of these techniques have failed if unable to provide immediate functional physiologic stability enabling immediate ambulation. Restoration of alignment is considered in both the frontal and sagittal plane such that the energy required to stand and walk is diminished with correct alignment. This goal is obtained with load bearing instrumentation that allows immediate mobilization as well as correction of deformity.

The posterior lateral approach is gaining popularity and allows for safe posterior access to the neural elements in the thoracic and lumbar region. The surgeon is able to address both the anterior and posterior columns simultaneously, as well as treatment of multi-level disease by multi-level stabilization. When compared to a two-stage procedure, there is noted to be decreased morbidity with a posterior lateral approach because of shorter operative time. The infection rate however may be higher.7 This surgical approach is ideal for a patient with limited life expectancy and the goal is to resect anterior tumour and stabilize posteriorly. However, if complete tumour resection is warranted then this should be done with a combined anterior surgery followed by posterior. The void left with removal of anterior column must be restored to maintain mechanical integrity. Cement usually provides adequate anterior column support. This must be complimented by posterior tension band which may consist of hooks and rods or pedicle screws and rods. Instrumentation when used in the treatment of spinal metastases should be MRI compatible.

The anterior surgical approach to the spine can be undertaken at all levels. In the past, there has been difficulty in obtaining access at the cervical thoracic junction and lumbosacral junction. These two anatomic areas have been shown to be accessible in a safe and reproducible manner. The cervical thoracic region can be approached by either a right or left sided approach and visualization from C7 to T4 can be obtained. The lumbosacral junction is routinely approached transperitoneally allowing anterior removal of tumour. There is still some difficulty in obtaining stable fixation anteriorly at this level and the procedure must be augmented by posterior instrumentation.

The biology of the anterior support is decided by the life expectancy of the patient and adjuvant therapy. It is generally accepted that the time to fusion with autograft of the spine is in the three to six month period. This may be affected by previous radiation as the soft tissue bed that accepts the graft is sub-optimal to allow ingress of pluri potential stem cells. Biologic incorporation may never occur with postoperative radiotherapy. Hence, patients with up to one-year life expectancy would probably benefit most from polymethylmethacrolate versus autograft allograft or cage. This is also more economically prudent. The complication rate in this patient population is high (20-30%).21 Chemotherapy serves to immunocompromise the patient, steroid serves to diminish wound healing capabilities, and radiotherapy diminishes the inflammatory responses of soft tissues. These three variables serve to act as major impetus for risk of infection and wound healing problems. This necessitates the use of broad spectrum prophylactic systemic and local antibiotics and meticulous wound closure with non absorbable suture. Intraoperative complications are primarily that of profuse bleeding, direct neurologic injury and poor fixation due to bone quality and tumour involvement. It is essential for the surgeon and oncologist to fully investigate the patient and optimize their nutritional and general medical status prior to surgery. Unfortunately, sometimes the necessity for urgent intervention precludes this.

As technology has allowed us to treat these patients more aggressively surgically, we must be mindful that the goal is to control pain, maintain and restore function, and optimize survival and therefore improve patient's health related quality-of-life. Recent studies have shown that surgical management of metastatic disease of the spine can obtain this.6,7,21 It is important to remember that treatment does not end with surgery and an aggressive approach to rehabilitation is necessary. This is sometimes optimally performed in a formal rehabilitation facility allowing greater strides in functional improvement.

In patients who are found to have unresectable lesions, the mainstay of palliative treatment is analysis, chemotherapy and/or radiotherapy. The relatively new technique of vertebroplasty to provide stability through a minimally invasive approach has promise, but effectiveness and indication are still being evaluated.
It is clear from our experience and the literature that after appropriate evaluation and sound decision-making, that the surgical treatment of metastatic disease of the spine is an essential and necessary option for these patients. There is, however, ample room for improving the current level of care through more interdisciplinary evaluation and reciprocating education with our oncologic colleagues. Furthermore, it is encumbant upon us to support well designed prospective studies to further validate the benefit of surgical treatment in this patient group. It is only with sound scientific evidence that spine surgeons can educate other physicians who manage these patients and thus collaboratively design a more optimal integrated paradigm for the evaluation and management of patients with spine metastases.

References

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5. Gaze M.M., et al: Pain relief and quality of life following radiotherapy for bone metastases: A randomized trial of two fractionation schedules. Radiotherapy and Oncology 1997;45:109-116.
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7. Jackson R.J., Gokaslan Z.L., Loh S.A.: Metastatic renal cell carcinoma of the spine: surgical treatment and results. Journal of Neurosurgery 2000:94;18-24
8. Kamra J.: Personal communication. Radiation Oncology Fellow. BCCA. April, 1999.
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10. Kostuik J.P., Errico T.J. et al: Spinal stabilization of vertebral column tumours. Spine 1988;13(3):250-256.
11. McLain R.F., Weinstein J.N.: Tumours of the spine. Seminars Spine Surgery. 1990;2:157-180.
12. Millburn L., Hibbs G.C., Hendrickson F.R.: Treatment of spinal cord compression from metastatic carcinoma. Cancer 1968;21:447-452.
13. Nielsen O.S., et al: Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastasis. Radiotherapy and Oncology 1998;47:233-240.
14. O'Connor M.I., Currier B.L.: Metastatic disease of the spine. Orthopaedics May 1992;15(5):611-620.
15. O'Donoghue D.S. et al: Orthopaedic management of structurally significant bone destruction in breast cancer bone metastases. JBJS (BR) 1997;79-B:Supp 1 pg 98.
16. Rao S., Badani K., Schildhauer T.: Metastatic malignancy of the cervical spine: A nonoperative history. Spine 1992;17(10S):S407-412.
17. Schaberg J., Gainor B.J.: A profile of metastatic carcinoma of the spine. Spine 1985;10:19-20.
18. Taneichi H., Kaneda K., et al: Risk factors and probability of vertebral body collapse in metastases of the thoracic and lumbar spine. Spine 1997;22(3):239-245.
19. Tokuhashi Y., et al: Scoring system for the preoperative evaluation of metastatic spine tumour prognosis. Spine 1990;15(11):1110-1113.
20. Wong D.A., Fornasier V.L., MacNab I.: Spinal metastasis: the obvious, the occult and the imposter. Spine 1990;15:1-4.
21. Zeznik L., Fisher C.G.: Health related quality-of-life in patients treated surgically for metastatic disease of the spine. Submitted for publication.

Fig. 1: A 58 year-old female with known metastatic adenocarcinoma to L1 presented with sever pain and progressive paraplegia. Anteroposterior (Fig. 1A) and lateral (Fig. 1B) radiographs reveal collapse of L1. MRI (Fig. 1C) reveal soft tissue epidural spinal cord compression. Postoperative anteroposterior (Fig. 1D) and lateral films (Fig. 1E) following a single stage posterolateral decompression and stabilization.

Figure 1A	Figure 1B	Figure 1C
Figure 1Ca	Figure 1d	Figure 1e