Advances in Surgery for Metastatic Disease of the Spine: An Update for Oncologists

Abstract

Study Design

Narrative review

Objective

Metastatic spine disease is an increasingly common clinical challenge that requires individualised multidisciplinary care from spine surgeons and oncologists. In this article, the authors describe the recent surgical advances in patients presenting with spinal metastases.

Methods

We present an overview of the presentation, assessment, and management of spinal metastases from the perspective of the spine surgeon, highlighting advances in surgical technology and techniques, to facilitate multidisciplinary care for this complex patient group. Neither institutional review board approval nor patient consent was needed for this review.

Results

Advances in radiotherapy delivery and systemic therapy (including immunotherapy and targeted therapy) have refined operative indications for decompression of neural structures and spinal stabilisation, while advances in surgical technology and technique enable these goals to be achieved with reduced morbidity. Formulating individualised management strategies that optimise outcome, while meeting patient goals and expectations, requires a comprehensive understanding of the factors important to patient management.

Conclusion

Keywords

Spinal Neoplasms metastases oncologist minimally invasive spine surgery Spine Instability Neoplastic Score spinal cord compression radiotherapy

Introduction

Spinal metastatic disease is a common clinical challenge. Between 20 and 40% of cancer patients will develop spinal metastases in their lifetime, of which 20% will become symptomatic.¹ It is likely these numbers will rise in years to come, as screening and surveillance imaging becomes more common, longevity increases due to advances in systemic therapy, and imaging techniques improve.

Patients with spinal metastatic disease require individualised multidisciplinary care including spinal surgeons, radiation oncologists, medical oncologists, radiologists, and palliative care physicians. The success of this care model is built upon a sympathetic understanding between disciplines of the factors important to patient management. Here we present the treatment paradigm from the perspective of the spinal surgeon, highlighting advances in surgical technology and techniques, to facilitate multidisciplinary care for this complex patient group.

Neither institutional review board approval nor patient consent was needed for this review.

Patient Presentation

Modes of presentation of metastatic spine disease are manifold, however they roughly fall into one of three categories: pain, neurology, or an incidental imaging finding

Incidental Imaging Finding

The incidence of incidental spinal metastases varies greatly in the literature, dependent on the predilection for skeletal metastasis of the primary histology, imaging modality, duration of disease, and population studied. In asymptomatic patients with known spinal metastases, one-third may have asymptomatic spinal cord compression on screening MRI.²

Spinal canal invasion is graded by the Spine Oncology Study Group (SOSG) grading system: Grade 1 is canal invasion without spinal cord compression, and is divided into 1a (thecal contact), 1b (thecal deformation), and 1c (cord contact). Grade 2 represents cord compression with some preserved CSF signal around the cord, while Grade 3 has complete CSF effacement. This is often dichotomised into low grade (grade 0-1) and high grade (2-3) metastatic epidural spinal cord compression (MESCC), the latter is a relative indication for surgery.

Early diagnosis of MESCC is important to prevent neurological worsening. Delays to the diagnosis of MESCC from onset of back pain may be 2-3 months, and 2-3 weeks from the onset of weakness, with delays understandably longer for those without a known malignancy.^3,4 Overall, 70% of patients with MESCC may have a preventable loss of function due to delays in symptom recognition and diagnosis. Despite the risk of irreversible neurological injury, prophylactic screening for MESCC has not been shown to improve outcomes in patients with spinal metastases.²

Pain

Back pain is a common finding in patients with spinal metastases, but also the general population. Pain may be classified as oncological, mechanical, or neurological, and clear delineation of the pain generator is of upmost importance to the spine surgeon.

Oncological pain is classically dull, poorly localised, and worse at night. The pathogenesis is multifactorial, due to periosteal stretch, microfractures, and cytokine release and proinflammatory pathways incited by the tumour locally. It is thought to be worse at night due to the nocturnal cortisol nadir, nocturnal hypercarbia (leading to vascular swelling), recumbency (which may affect venous drainage), and the absence of distractors. Generally, it responds well to anti-inflammatories (NSAIDs and glucocorticoids).

Discerning the presence of mechanical pain is one of most important parts of the clinical history, as it is the clinical manifestation of biomechanical instability. Mechanical pain is incited by loading of the spine in a vector that stresses skeletal, ligamentous, and muscular structures that have been eroded by tumour. Although commonly elicited by axial loading and walking, the specific movement generating mechanical pain may depend on the location of the metastasis, such as flexion, extension, and rotation of the neck for cervical lesions, and recumbency for thoracic lesions. Lumbar lesions may cause mechanical radicular pain due to listhesis on axial loading.

Neurological pain is due to compression of the neural elements by tumour. Radicular pain is the result of nerve root compression, and is characterized as unilateral, lancinating, dermatomal pain and paraesthesia that may be exacerbated by Valsalva manoeuvre. With time, anaesthesia and hyperesthesia may develop in the effected dermatome, followed by atrophy or fasciculations in the corresponding myotome. Commonly, patients with thoracic radicular compression complain of band-like “tightness” around the torso. Funicular pain is caused by compression of the ascending spinothalamic and dorsal columns within the spinal cord, and may manifest as deep and ill-defined dysesthesias usually quite remote from the compressed level.⁵

Neurology

Compression of the spinal cord manifests as myelopathy, weakness, and long tract signs (spasticity, hyperreflexia, proprioceptive loss and ascending numbness and paraesthesias with or without a sensory level). Myelopathy may coexist with radiculopathy (myelo-radiculopathy), which localises the level of compression. The conus lies at the upper lumbar spine, and compression here leads flaccid paraplegia with sphincter dysfunction. More caudal compromise of the spinal canal can manifest as cauda equina syndrome.

Patient Assessment and Consulting a Spine Surgeon

The NOMS (neurologic, oncologic, mechanicals stability, and systemic disease) framework facilitates decision making in spinal metastatic disease⁶ (Figure 1 and Table 1).

Table 1.

Workup at time of diagnosis of MESCC.

Workup at time of diagnosis of MESCC
All patients
MRI whole spine (with gadolinium)
CT myelogram if contraindicated
CT whole spine (without contrast)
Preoperative bloods (FBE UEC Coags G+H)
Withhold all anti-thrombotics and fast until operative plan confirmed
Known primary malignancy
Restage
CT CAP vs PET vs bone scan
Tumor markers (if appropriate
Oncological history
Prior and current systemic therapy and radiation regimens
No known primary malignancy
Stage
CT CAP vs PET vs bone scan
Core biopsy of lesion
Restaging and percutaneous biopsy should not delay surgery if patient is clinically myelopathic or unstable

MESCC = Metastatic epidural spinal cord compression; FBE = Full blood examination; UEC = Urea, creatinine and electrolytes; G + H = group and hold; CAP = Chest, abdomen and pelvis; PET = Positron emission tomography

Neurological

Clinical examination assesses for the presence of radiculopathy, myelopathy, and sphincter dysfunction, while the history provides the duration and tempo of the neurological decline, which is important in predicting functional outcome. Generally, the more severe and chronic the deficit, the less likely it is to recover. Similar to the trauma literature, patients with complete motor involvement are unlikely to ambulate again, but some patients with non-ambulatory paraparesis may regain the ability to walk.⁷

The presence of neurology should prompt an urgent MRI of the whole spine and spine surgery consult. A CT scan is often complementary as it depicts the bony anatomy better and is particularly useful in cases of spinal metastases which commonly have resultant bony destruction, vertebral body collapse or kyphotic deformity. A good understanding of anatomy is particularly important for accurate instrumentation, especially in centers without intraoperative navigation.

Oncological

Foremost, tumour histology should be established. In patients presenting with acute neurology or instability, biopsy can be performed intraoperatively. In patients without an immediate indication for surgery, percutaneous CT guided biopsy is safe and effective.⁸

The advent of stereotactic body radiotherapy (SBRT) has changed the landscape of treatment for MESCC. While the efficacy of external beam radiotherapy (EBRT) is dependent on the relative “radiosensitivity” of the tumour histology, the ability of SBRT to deliver high doses at submillimeter accuracy facilitates its efficacy independent of histology,^9,10 by targeting tumoral vasculature.¹¹ Radiosensitive tumors (haematological and germ cell malignancies) are still treated with EBRT, while most solid organ metastases are managed with SBRT. SBRT has demonstrated superior pain outcomes compared to EBRT,¹² and is effective on a broad range of histologies.

Patients’ presentation must be contextualised within their oncological journey. A thorough understanding of tumour biology, including previous treatment, the available of suitable targeted therapies, the remaining armamentarium of systemic therapy available, and systemic burden of disease are vital to setting appropriate goals of care. Patients should also be restaged at the time of MESCC diagnosis.

Mechanical

Spinal instability occurs due to a “loss of spinal integrity as a result of a neoplastic process that is associated with movement-related pain, symptomatic progressive deformity, and/or neural compromise under physiological loads”.¹³ Mechanical pain is the clinical manifestation of instability, and any patient with mechanical pain should be presumed to unstable until proven otherwise. Radiological evidence of instability, such as new subluxation, translation, or deformity are similarly indications for stabilisation. The Spine Instability Neoplastic Score (SINS) is a useful tool incorporating pain characteristics, and radiological alignment as well as location, bone character, and anterior column and posterior element involvement to help identify which patients should be referred for a spine consult.¹³ Here, CT imaging of the spinal region of interest, accompanied with complementary MRI, can be invaluable in radiological assessment of spinal bony construct. Spinal stabilisation is the only definitive treatment for mechanical pain.¹⁴

Systemic

Wholistic assessment requires an understanding of life expectancy, performance status, frailty, and most importantly, the patient’s and family’s desires and expectations of care. Life expectancy can be estimated using Spine Oncology Research Group (SORG) nomogram,¹⁵ which is useful at predicting 3 and 12 month mortality. However, early mortality, within 30-days of surgery, appears more dependent on patient frailty rather than oncological factors.¹⁶

Frailty is a state of physiological vulnerability that renders patients susceptible to adverse outcomes.¹⁷ Common markers of frailty such as older age, accumulated medical comorbidities, malnutrition (hypoalbuminemia), and poor functional status are predictors of poor outcome in spinal metastases.^18,19,20 Frailty can be assessed clinically, such as anthropomorphic assessment of sarcopaenia, functional status, malnutrition, or the timeless “end of the bed” assessment; biochemically, such as serum haemoglobin or albumin levels; and radiologically, with psoas cross-sectional area.²¹ Frailty has been associated with increased length of stay, inpatient complications, and mortality in spinal metastatic surgery.²² A specific frailty index for metastatic spine disease has also been developed and validated.²³

Indications for Surgery

Definitive indications for surgery are clinical myelopathy and spinal instability (Table 2). High grade radiological MESCC, impending instability, tissue diagnosis, and recurrent tumours should also prompt surgical consultation (Table 3).

Table 2.

Indications for surgery in spinal metastases.

Indications for surgery in spinal metastases
Absolute
Clinical Myelopathy
Spinal instability
Relative
Asymptomatic high grade cord compression (SOSG grades 2* and 3)
Tissue diagnosis after failed IR biopsy
Oligometastatic disease in radioresistant tumour

SOSG = Spine Oncology Study group; IR = Interventional radiology

= SOSG grade 2 disease can be treated with SRS in under specific circumstances

Table 3.

Indications for spine surgery consultation.

Indications for spine surgery consultation
Neurology
Myelopathy
Radiculopathy
Radiological high grade cord compression (SOSG Grade 1C and above)
Instability
Mechanical pain
Deformity or translation/subluxation
SINS score ≥7
Inability to obtain tissue diagnosis
Concern for a primary bone tumour

SOSG = Spine Oncology Study group; SINS = Spinal instability neoplastic score

The presence of myelopathy should prompt an urgent surgical consultation and MRI of the whole spine. Patients with myelopathy of <48 h duration from solid organ malignancy MESCC have better neurological and functional outcomes as well as longer overall survival with surgery followed by radiotherapy compared to radiotherapy alone.²⁴ Highly radiosensitive (haematological and germ-cell) tumours with stable, mild symptoms can be trialled with EBRT alone. In all other cases, decompression surgery followed by EBRT is standard. The introduction of SBRT has meant extensive (morbid) resections of radioresistant tumours can be replaced by separation surgery, which debulks epidural tumour to create a tumour-free plane of 2-3 mm around the theca, followed by SBRT.²⁵ For patients without symptoms, but high-grade MESCC (SOSG Grade 2-3), separation surgery is also recommended to ensure good tumour control while minimising cord irradiation.²⁶ In specific cases, SOSG Grade 2 MESCC can be treated with SBRT alone with excellent results.²⁷

Instability is an independent indication for surgery and may be diagnosed by the presence of mechanical pain, deformity or subluxation/translation. Patients with indeterminant or high SINS scores (≥7) should be referred to a spinal surgeon for assessment. Patients with “impending” instability can be offered prophylactic stabilisation in specific circumstances, particularly as SBRT can induce insufficiency fractures.²⁸ Fixation can be performed percutaneously if no decompression/separation is required with comparative outcome and less morbidity than open techniques.^29,30 Metastases involving craniovertebral junction can be complex biomechanically, and expert spinal surgery opinion should be sought early due to risks of instability.

Nerve root compression with resultant intractable radicular pain or radiculopathy is another potential surgical indication, however the literature is scant. Surgical treatment in this context primarily aims to decompress the involved nerve root/s, which may require a concurrent instrumented fixation especially if facetectomy is required for adequate decompression. Other surgical options include dorsal rhizotomy and dorsal column myelotomy, which are palliative procedures performed for pain relief; these lesioning procedures are rarely performed. Radiotherapy can present as an effective alternative, especially for patients presenting with radicular pain without weakness. Selection between surgical intervention and radiotherapy requires consideration of several factors, including the severity of myotomal weakness (if any), presence of leptomeningeal disease (versus that of epidural compression of nerve root), radiosensitivity of the neoplastic process, extent of systemic metastases, overall prognosis of the patient, and current functional status.

Updates in Surgical Care

Paralleling advances in systemic and radiation therapies, technological advances in minimally invasive surgery, wound management, and instrumentation have improved outcomes for patients requiring surgery for MESCC.

Minimally Invasive Surgery

Minimally invasive surgical (MIS) approaches utilise smaller incisions to reduce morbidity and may broaden operative suitability to those too frail for traditional open approaches. MIS approaches are associated with less intraoperative blood loss, shorter hospital stay, and less complications while providing functional outcomes equivalent to open surgery.^31,32,33 Percutaneous instrumentation,³⁰,³⁴ mini-open approaches,³⁵ thorascopic and endoscopic decompression, and the use of minimally invasive tubular retractors are all examples of MIS techniques. For open approaches, the rate of wound complications increase by 21% per operative level,³⁶ and thus minimising wound length with MIS is important in this vulnerable population.

For those with painful pathological fractures that are biomechanically stable or are not suitable for fixation, percutaneous vertebroplasty with or without kyphoplasty is associated with reduced pain and improved functional outcomes compared to conservative management.³⁷

Neuronavigation

Neuronavigation involves real-time mapping of the operative exposure to 3-dimensional imaging acquired intraoperatively. This facilitates percutaneous pedicle screw fixation with much higher accuracy than traditional techniques.³⁸ Neuronavigation can be particularly useful in MESCC cases as deformity, instability, and tumour may obscure traditional landmarks. Improvements in the speed, accuracy, radiation dosing, and imaging quality of intraoperative neuronavigation has encouraged wider adoption of MIS techniques for spine tumour surgery. Robotic-assisted surgery, is a new advance that can assist in accurate pedicle screw placement and reduce surgical time. Future directions of neuronavigation include augmented reality, where clinicians visualize the screw trajectory and the operative field simultaneously, improving accuracy and operative ergonomics.³⁹

Instrumentation

Failure of instrumentation is the second most common cause for reoperation in patients undergoing surgery for spinal metastases.⁴⁰ Longer survival is commonly associated with hardware failure, suggesting this complication may become more prevalent as systemic therapies continue to improve.^41,42 Bony fusion rates in metastatic spine disease are much lower than in degenerative pathology, likely due to compromised bone healing from radiation, tumour infiltration, and higher rates of premorbid osteoporosis.⁴³ New mechanical back pain may herald hardware failure in an instrumented patient.

General principles of spinal instrumentation remain valid in the context of spinal metastases. However, due to altered vertebral biology and need for radiotherapy, longer construct and larger sized pedicle screws should be considered, especially in the presence of diseased adjacent levels.

Efforts had also been made to utilize different material for instrumentations. This include carbon fibre-reinforced material, which is available as cages, screws, rods and plates. In comparison to titanium implants, these carbon fibre based systems produce less imaging artefact which facilitates improved surveillance imaging, radiotherapy planning, and potentially greater safety and efficacy of EBRT and SBRT.⁴⁴ Additionally, the elastic modulus more closely approximates native bone, which may improve biomechanics and promote fusion.⁴⁵

Wound Healing

Wound complications in patients with metastatic spinal disease occur at almost twice the rate of degenerative pathology,⁴⁶ and are the most common reason for reoperation.⁴⁰ Risk factors include high dose perioperative glucocorticoid administration, premorbid or glucocorticoid induced diabetes mellitus, longer incisions, malnutrition cachexia, sarcopenia, higher prevalence of tobacco use, older population, cancer related immunosuppression, longer hospital stays, as well as radiation and systemic therapy.^36,47,48

Radiotherapy effects wound microvasculature and alters levels of transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), and proinflammatory cytokines during the inflammatory and proliferative stages of wound healing. This results in tissue matrix accumulation, fibrosis, impaired collagen deposition, and greater susceptibility to infection.^49,50 Earlier commencement of radiotherapy improves outcome,⁹ but may increase the risk of wound complication.⁵¹ Generally, an interval of two weeks is preferred, but evidence is lacking.⁵² Neoadjuvant stereotactic radiotherapy had also been proposed, which allowed for accurate tumor volume contouring and more predictable dose delivery, without increasing risks of significant wound complications. This however remains to be based on small case series,⁵³ and will need to be investigated in larger studies. Systemic therapy should generally be discontinued during the perioperative period, but immunotherapy and most targeted therapies (except those that target VEGF/Angiogenesis pathways) can be continued (Table 4).

Table 4.

Perioperative management of systemic therapy.

Perioperative management of systemic therapy
Can continue
Immunotherapy (PD-1, PDL1, CTLA4 inhibitors)
Small molecule TKIs
Anti-hormonal therapy
Targeted therapies
HER-2 (trastuzumab, pertuzumab)
BRAF, MEK and KIT
Discontinue for 4 weeks pre- and post-surgery
Anti-VEGF therapy (Bevacizumab)
Conventional chemotherapy
Rituximab

PD-1 = Programmed cell death protein 1; PDL-1 = Programmed cell death protein ligand; CTLA-4 = Cytotoxic T lymphocyte associated protein 4, TKI = Tyrosine kinase inhibitor; HER-2 = human epidermal growth factor receptor 2; VEGF = Vascular endothelial growth factor

Other advances in wound care include topical vancomycin powder, negative pressure wound therapy (NPWT) and minimally invasive surgery. NPWT provides a sub-atmospheric pressure around the wound, evacuating interstitial fluid, and improving lymphatic drainage and microvascular blood flow to accelerate wound healing. Experience in degenerative⁵⁴ and metastatic⁵⁵ spine disease has been promising. Intraoperative topical vancomycin is a relatively safe and easily implementable intervention to prevent surgical site infection. In small uncontrolled cohorts of patients with spinal metastatic disease, it has shown a favourable infection prevention profile.⁵⁶

Conclusion

Spinal metastases require prompt diagnosis and expert management by a multidisciplinary team. Improvements in systemic, radiation, and surgical therapies have broadened operative indications and increased operative candidacy, and future advances are likely to continue this trend. We have summarised the important considerations for operative intervention in MESCC and surgical innovations that may improve outcome for this vulnerable group.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Tony Goldschlager

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