Spinal Metastasis Treatment & Management

Updated: Nov 26, 2018
  • Author: Victor Tse, MD, PhD; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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Treatment

Medical Care

No treatment has been proven to increase the life expectancy of patients with spinal metastasis. The goals of therapy are pain control and functional preservation. The most important prognostic indicator for spinal metastases is the initial functional score. The ability to ambulate at the time of presentation is a favorable prognostic sign. Loss of sphincter control is a poor prognostic feature and mostly irreversible. Other problems associated with metastatic disease include pain related to pathologic fractures, hypercalcemia, and psychological problems.

Treatment decisions for patients with spinal metastases can be challenging, and survival prognosis should be considered when determining the best course of action. In a retrospective study, Wibmer et al examined prognostic scoring systems (Bauer, Bauer modified, Tokuhashi, Tokuhashi revised, Tomita, van der Linden, and Sioutos) in 254 spinal metastases patients. [3] The Bauer and Bauer modified scores were better predictors of survival. Factors associated with better prognosis with survival of more than 3 months and improved quality of life included location of the primary tumor, extent of visceral metastases, and systemic chemotherapy adverse effects.

This discussion focuses on the management of pain, structural stability, local disease, and hypercalcemia. Medical management that addresses the systemic disease, such as chemotherapy and hormonal therapy, are not discussed. Hormonal manipulation, such as the use of tamoxifen to treat breast cancer, preserves bone mineralization because of its estrogen-agonistic effect.

Treatment of pain

Patients with spinal metastasis commonly have bone pain. Their pain may be related to bone destruction or pathologic fractures. Local pain is due to stretching of the periosteum and may respond to irradiation or use of corticosteroids. Axial pain can occur when vertebral compression and/or collapse occurs. Axial pain is secondary to mechanical instability. It causes distress and reduces mobility of the patients. In addition, a number of these patients have neuropathic pain. This pain may be related to root irritation and/or meningeal irritation secondary to cancer infiltration. Both steroids and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage bone pain. Use of spinal orthotics and physiotherapy are useful adjuvant therapies for this group of patients.

Steroid therapy is effective in treating bone pain. Immediate treatment is high-dose dexamethasone. The optimal dose has not been established. However, in practice, the usual dose is a loading dose of 10 mg then 4 mg every 6 hours. Of all the corticosteroids, dexamethasone has the least mineralocorticoid effect and is least likely to be associated with infection or cognitive dysfunction, though it does increase the risk of myopathy. Other adverse effects include psychotic reaction (5%), GI bleeding (< 1%), and glucose intolerance (19%).

The frequency of complications from steroid therapy depends on the duration of the treatment and is associated with hypoalbuminemia. Treatment lasting more than 3 weeks is more likely to be associated with complications. Hypoalbuminemia appears to increase the risks of adverse effects associated with steroid treatment.

In about 70–80% of patients, symptoms improve within 48 hours of treatment. Approximately 64% of patients report alleviation of pain within 24–48 hours of starting steroid therapy, and 57% report improvement in their motor function. In most patients, steroid use must be continued until radiotherapy is completed.

Treatment of neuropathic pain

Emerging evidence shows that antiepileptic drugs are effective in treating pain. Gabapentin is frequently used to treat neuropathic pain and is well tolerated. Other drugs, such as lamotrigine, carbamazepine, levetiracetam, tiagabine, and topiramate have also been used; tricyclic antidepressants are still being used to treat neuropathic pain. However, tricyclic antidepressants cause more adverse effects than the aforementioned antiepileptics.

Topical preparations, such as the lidocaine patch, are less effective than the drugs previously mentioned. Opioid analgesic is useful. The concern about addiction and tolerance with long-term use should not be a major concern in patients with cancer. Chemical epidural neurolysis was infrequently used to treat medically intractable pain. It is effective for interrupting single or multiple radicular pains, but it poses a risk of acute deterioration especially when structural instability or compression is present.

Vertebral augmentation procedures aid with pathologic compression fracture management. Minimally invasive and open surgical decompression and stabilization techniques are used for mechanical pain. Tumor ablation procedures, including radiofrequency, cryoablation, thermal ablation, and laser interstitial thermal therapy (LITT), are indicated in patients with severe biologic pain. Finally, spinothalamic tractotomy or cordotomy are available procedures for pain in cancer patients, though not commonly used to treat spinal metastatic diseases. Radiation therapy is also effective in treating pain caused by bone metastasis. Additionally, radiofrequency ablation within the tumor may help reduce tumor size; this can be done within the vertebral body, pedicles, and paraspinal musculature. [4]  Alternatively, various neuromodulation techniques (deep brain and dorsal column stimulation, intrathecal modulation) exist to ameliorate the various pain syndromes associated with tumors. [5]  Finally, cordotomy and various tractotomy techniques exist but are fraught with significant complications. [6]  

Hypercalcemia

Hypercalcemia is particularly common in patients with lytic metastasis, and it is not infrequently found in those with paraneoplastic syndrome that produces parathyroid hormone–related protein. Patients with hypercalcemia commonly present with polyuria, and some, with pre-renal failure. Initial treatment should be rehydration and administration of a steroid. Bisphosphonate is useful to control the lytic process. It inhibits osteoclast function, decreasing bone resorption.

Next:

Surgical Care

The main goals of surgical care in the cancer patient with metastatic spinal disease include decompression to preserve function and stabilization to reduce mechanical pain and to prevent or correct spinal deformity. Ancillary goals include local disease control and facilitation of radiosurgical treatment. Surgical intervention with extensive reconstruction should be performed only after thorough evaluation of the extent of the systemic disease and with a clear understanding of the realistic expectations of the patients and their caretakers. Radiotherapy and surgical resection (spondylectomy or intralesional resection) are now the preferred treatments to control local disease.

The aim of decompression is to preserve neurological function related to neoplastic compression of the cord, nerve roots, or both. Decompression may be focal such as a laminectomy (when posterior compression alone without instability) or foraminotomy, but can also be extensive involving decompression of the anterior spinal cord with concomitant circumferential fixation. In the setting of extensive epidural disease, decompression facilitates radiotherapy; termed “separation surgery,” creating space between the tumor and spinal cord facilitates higher doses of radiation to tumor while reducing cord toxicity. Decompression is often paired with stabilization due to the extensive anterior and middle column destruction as well as poor bone quality related to tumor invasion.

Every patient with a spinal metastasis and pain should be evaluated for mechanical instability. The Spinal Instability Neoplastic Score (SINS) [7]  is a helpful guide to determine whether the pain complaint is mechanical in nature. Classically, mechanical back pain is described as pain with loading the spine, which is relieved when unloaded. Vertebral cement augmentation techniques may be used to help alleviate pain; these can be performed in a standalone fashion or as an adjunct to open stabilization. 

In the case of pathologic compression fractures where the compression fracture involves the anterior spine, vertebral cement augmentation is an option. Using image-guidance, the pedicle is cannulated and the vertebral body injected with cement; the process is exothermic and thus antineoplastic locally and is typically an outpatient procedure. It can be used as an adjunct to open stabilization. 

Aggressive, en-bloc tumor resection is not recommended universally due to the significant increase in morbidity and mortality as compared to intralesional resection; four-year results are comparable. Minimally invasive or open surgical reconstruction is used to decompress the neural elements, provide stabilization, and correct the spinal deformity. Level-1 evidence supports the role of surgical decompression and stabilization, followed by radiotherapy in patients with metastatic spinal cord compression. [8]  Stabilization should be considered for mechanical pain where vertebral augmentation is contraindicated or where progressive deformity causes debilitation. Minimally invasive, percutaneous options are available for providing stability and to reduce the size of the incision that will undergo irradiation but may not allow for an adequate working channel to decompress the spinal cord. 

General considerations in controlling local disease

Radiation therapy is more effective in achieving pain control (67%) than surgery (36%). Of note, surgery alone is the least effective way to treat spinal metastases. About 20-26% of patients who undergo surgery have further deterioration in terms of mobility or sphincter control, whereas 17% of those receiving radiation therapy have further deterioration.

The advancement of minimally invasive surgery and of new forms of stereotactic radiosurgery has radically changed the management paradigm of metastasis disease to the spine. Current thinking is to perform early radical resection of a single lesion in the spine and to administer adjuvant stereotactic radiation therapy to eradicate the disease. This approach allows for decompression, stabilization, and suppression of local recurrence.

Indications for surgery and radiotherapy

The traditional treatment for spinal metastasis is radiation and/or steroids. In rare cases, surgery is advocated as a last resort. Recent studies, however, support a combined approach with surgery and radiation. The goals are to achieve bony and neuronal decompression, preserve function, and stabilize to reduce mechanical pain and to prevent or correct spinal deformity. Secondary goals include local disease control and facilitation of radiation therapy/radiosurgical treatment. 

Radiotherapy

Radiotherapy remains the mainstay of treatment for spinal metastatic disease. Most of lymphoreticular tumors and prostate carcinoma are relatively insensitive; lung and breast are relatively insensitive. Tumors of the GI system and kidney are resistant to radiotherapy, as are melanomas. Nevertheless, radiotherapy elicits some response in melanomas. About 80% of patients with pretreatment pain have symptomatic relief; 48% of patients with motor or sphincteric dysfunction respond to treatment.

The common regimen is 30 Gy in 10 fractions. The amount of radiation is empirical and based on the therapeutic ratio, a function of the fractionation dose and biologically effective dose, as well as the tolerance dose of the spinal cord and its associated vasculature, roots, and marrow. The tolerance dose for specific tissue is a function of irradiation volume, the total dose per fraction used, and the level of risk acceptable. The effect of irradiation depends on the proliferative power of the tissue. Hence, skin and bone marrow are affected early, whereas brain and spinal cord are affected late. A subacute effect is due to demyelination secondary to injury to the oligodendrocytes and the vascular tree. For example, the traditional fractionated dose for cord necrosis is 1.8-2.0 cGy/d.

The efficacy of dose fractionation is derived from biologic reasoning, as follows:

  • Repair of sublethal damage: The biologically effective dose is the probability of cell survival after single doses of ionizing radiation. It is a function of the absorbed dose measured in grays and based on the simple fact that irradiation causes double-stranded DNA to break. However, the dose for a single particle to cause a double-strand break is low, whereas that for a single-strand break is high. Yet two single-strand breaks occurring closely in space and time may result in double-strand disruption with lethality similar to that of double-strand break and therefore deemed irreparable.

  • Reoxygenation of hypoxic cells: Reoxygenation is important because tumor has hypoxic cells, and the fraction of hypoxic cells increase after irradiation. Oxygen is the most powerful radiation sensitizer. Hypoxic cells are radiation resistant by as much as a factor of 3.

  • Reassortment of proliferating cells in the cell cycle and repopulation: A single fraction of irradiation eliminates a portion of cells in the G2 and M phases. However, in the next 4-6 hours the cell population resumes cycling and redistribution. The radiation sensitivity varies over the cell cycle by as much as a factor of 3. Hence, with a standard dose is 30-60 Gy. About 18% of patients have a risk of myelopathy.

Advancement in CT and/or MRI-based planning improves the precision of information regarding the location of tumor and critical normal structures. The traditional treatment plan, or radiation port, is to include 2 vertebral bodies above and 2 below the lesion. This range is based on the fact that recurrence is most common in bodies contiguous to the site of involvement. These advancements in image-guided target radiotherapy led to the development of intensity-modulated radiation therapy (IMRT) stereotactic radiosurgery.

IMRT can deliver irradiation with optimized nonuniform intensities in each radiation field. It improves conformation to the tumor and helps spare normal tissue. The advantage is that it can generate concave and complex dose distributions. IMRT optimizes the 3 dimensional (3D) planning system and includes reverse planning to best deliver a modulated beam-fluence profile. It is accurate to 12-15 mm.

The use of stereotactic radiosurgery and IMRT to treat spinal metastasis has become increasingly common.

Over last two decades, the emerging technology allows the use of a robotic linear accelerator (LINAC) that can move freely in 3D space (CyberKnife: Accuray, Sunnyvale, CA). This method increases the number of possible beam orientations. Real-time target tracking allows for movement within 1 mm of spatial accuracy. In addition, this form of irradiation therapy has the following advantages:

  • It is a frameless system.

  • It references the target to internal landmarks (eg, radiographic anatomic features, bony landmarks, implanted fiducials).

  • It tracks with a real-time imaging device and dynamically aligns the target with the beams.

  • It aims each beam individually.

The present author favors use of this robotic technology in the treatment of spinal metastasis. Thus, delivering a relatively high dose of radiation to a small target with rapid dose fall-off is feasible. Highly conformal beams guided with 3D imaging are used, which gives accuracy down to submillimeter (0.4-0.7 mm).

A study from the Radiation Therapy Oncology Group (RTOG97-14) showed that 50-80% of patients have adequate pain control in 3 months with single-fraction irradiation. About 78% patients treated with irradiation remained ambulatory, and 16% of nonambulatory patients and 4% of patients with paralysis regained function. Among those treated with laminectomy followed by irradiation, 83% who were ambulatory remained so, while 29% of nonambulatory patients and 13% of patients with paralysis regained function. In a reasonably sized study reported by Dwright et al, [9] single-session stereotactic radiosurgery seemed to have a better pain control rate and multiple sessions of radiosurgery seems to have a better control rate at 96% vs 70%.

Radial surgery and spinal stabilization

Surgical intervention for spinal metastases serves two major roles: decompression of neural elements and creation of space for maximal SRS dosing. The first has been previously discussed in detail. Separation surgery, the process of decompressing the cord of tumor, allows for reduced cord toxicity as a result of tumor irradiation by creating as little as 2 mm of space between the tumor and the thecal sac. Typically this is done via a transpedicular approach, which is inherently destabilizing; thus fixation is performed, which may help with any underlying instability. [10]  

The Spine Oncology Study Group (SOSG) defines spine instability as the “loss of spinal integrity as a result of a neoplastic process that is associated with movement-related pain, symptomatic or progressive deformity and/or neural compromise under physiological loads." Surgery is indicated as a stabilization procedure and/or for tissue diagnosis. It is also used in some cases where cord compression is eminent or has occurred. In the past, surgery was only considered in patients with disease that progressed despite radiotherapy and in those with tumors known to be resistant to radiotherapy. Now, some surgeons have advocated vertebral-body resection and stabilization as a preventive measure for eminent spinal instability and/or supplementation for radiation therapy. [7]

Axial pain secondary to mechanical instability can causes significant morbidity. In this circumstance, spinal stabilization is the treatment of choice. With the advancement in spinal stabilization, satisfactory neurologic improvement occurs in 48%–88% of patients, with 80%–100% rates of pain relief. On the contrary, radiation therapy cannot reverse compression secondary to bone, and the therapeutic response is delayed several days, even in patients with highly radiosensitive tumors (eg, lymphoma, neuroblastoma, seminoma, myeloma).

Extensive resection with fixation surgery not only provides stabilization, it also confers tissue diagnosis and reduces tumor burden. It is particularly beneficial in patients whose disease progresses despite radiotherapy and in those with known radiotherapy-resistant tumors. Surgical decompression and stabilization, with radiotherapy, is the most promising treatment. It stabilizes the diseased bone and allows ambulation with pain relief, preservation of continence, decreased loss in Frankel score, and increased survival time. Vertebral-body resection and anterior stabilization with cement agumentation and/or hardware (eg, titanium cages) reconstruction are commonly used as previously discussed. This may be supplemented with posterior short segment instrumentation using screws and rods constructs.

In general, patients who are nonambulatory at diagnosis do poorly, as do patients in whom more than 1 vertebra is involved. Radical resection is indicated in patients with radiation-resistant tumors, spinal instability, spinal compression with bone or disk fragments, progressive neurologic deterioration, previous radiation exposure, and uncertain diagnosis that requires tissue diagnosis. The goal is always palliative rather than curative. The primary aim is pain relief and improved mobility.

In brief, the authors advocate separation surgery in cases of canal involvement and neurological compression to facilitate radiotherapy. Cement augmentation should be considered for anterior column–limited disease with pathologic compression. Decompression with stabilization affords multiple benefits in cases of epidural cord compression. Tumor ablation procedures may also be considered as palliative measures where medication or radiation are contraindicated or no longer tolerated.  Oncological and systemic considerations of tumor histology, radiosensitivity, disease status, and life expectancy should also be factored. Hence patients with breast, thyroid, prostate, or renal carcinoma are better candidates than those with melanoma and lung cancer. In published series, experienced surgeons used a radical, simultaneous anterior–posterior approach with resection of the tumor (en-bloc spondylectomy), reconstruction, and stabilization.

Surgical Approaches

Laminectomy

Laminectomy is indicated less often than the other procedures described because most lesions are anteriorly based, and posterior decompression may further destabilize the spine. Laminectomy does not address the anterior and middle columns (in the Denis 3-column model of the spine) and may further compromise spinal stability. With laminectomy, postoperative mortality is 10–15%, and morbidity (wound) can be as high as 35%. Posterior decompression alone is not a good solution in most cases of spinal metastasis; the metastasis tumors are most commonly deposited anteriorly because of the anatomic involvement of the disease. Even when the tumor involves the posterior lateral aspect of the spine, posterior decompression provides no additional relief or substantial functional advantage. This approach was evaluated in 84 patients with predominantly dorsal epidural disease. Before surgery, 80% were nonambulatory, and 56% had sphincter dysfunction. After surgery, the overall morbidity rate was 45%, and none of the patients regained neurologic function. The complication rate was 4.7%. However, laminectomy supplemented with stabilization with neutralizing fixation devices, such as pedicle screws, does offer pain relief and a degree of functional recovery in a substantial number of patients.

Transpedicular approach

The transpedicular approach is popular when tumor involves the dorsal aspect of the vertebral body, especially when the disease extends into the pedicle and associated dorsal elements. Facetectomy coupled with pediculectomy allows access into the vertebral body. This is the favored approach for performing separation surgery and is inherently destabilizing to the spine. Followed with instrumentation above and below depending on location and bone quality, this procedure provides an excellent surgical result. Some surgeons suggest that bilateral pediculectomy allows for complete vertebrectomy (spondylectomy), and anterior augmentation with polymethylmethacrylate (PMMA) and plating optimizes surgical goals. However, in some studies, the overall complication rate was high as 50%.

Posterior approach

The advantages of the posterior approach is (1) it permits early identification of the cord, (2) it can address diseased dorsal elements, (3) it allows the use of rigid constructs or long constructs in posterior areas, and (4) it addresses imbalance of the sagittal plane and pain due to micro instability.

Costotransversectomy and lateral extracavitary approach

These are posterior lateral approaches that can gain access to the dorsal part of the vertebral body while minimizing spinal cord manipulation.

Minimally invasive endoscopic procedures

Some have recently advocated the uses of minimally invasive approaches, including endoscopy-assisted spinal-cord decompression, percutaneous vertebroplasty and/or kyphoplasty (variation on cement augmentation), minimally invasive image-guided tumoral resection and spinal reconstruction, and percutaneous approach to place pedicle screws. These techniques have revolutionized the surgical management of spinal metastatic disease. Considering that most operative patients will progress to radiation treatment, smaller incision and muscle splitting techniques allow for faster recovery after percutaneous stabilization.

Kyphoplasty

Kyphoplasty is a minimally invasive procedure that may play a pivotal role in the treatment of spinal metastases. In a single procedure, the operator can gain access to the vertebral body by means of the pedicles to sample or remove a reasonable amount of tumor. An infusion of PMMA into the affected bone stabilizes and/or restores the diseased bone. This modality can be used in patients with an unfavorable health status and may not be suitable for other forms of open surgery. Kyphoplasty has been used as a conjoined therapy for posterolateral stabilization surgery. Kyphoplasty can also been used as a standalone structural stabilization therapy for pathological compression fractures in cancer patients. It has been proven to be very effective (84–90%) in relieving acute pain due to pathological fracture especially in patients with competent posterior tension band. 

Radical en-bloc spondylectomy and reconstruction

This is the most aggressive approach in the surgical armamentarium. It intends to perform an en-bloc excision of the affected vertebral body and stabilize the spine anteriorly and posteriorly with instrumentation. In the cervical spine this includes skeletonizing of the vertebral arteries. Typically, tumor involvement must not include the pedicles to allow for detachment of the vertebral body from the posterior elements.

The overall outcome of surgical intervention is rather controversial. In one national statistical study, the in-hospital mortality rate was reported as 5.6%, and the complication rate was 21.9%. [11] Unfortunately, in this study, the authors failed to address the complications and socioeconomic impact on patients and their families and caregivers when patients are treated conservatively. In another multinational study, a cost-effective analysis favored early surgical intervention. [12]

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