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Updated: Sep 7 2021

Metastatic Disease of Spine

  • Introduction
    • Metastatic cancer is the most common reason for a destructive bone lesion in adults
      • carcinomas that commonly spread to bone include
        • breast (16-37% of breast cancer patients develop spine mets)
        • lung (12-15%)
        • thyroid (4%)
        • renal (3-6%)
        • prostate (9-15%)
  • Epidemiology
    • Incidence
      • bone is the 3rd most common site for metastatic disease (behind lung and liver)
    • Demographics
      • metastatic bone lesions are usually found in older patients (> 40 yrs)
    • Anatomic location
      • common sites of metastatic lesions include spine>proximal femur>humerus
        • most common site of mets is spine
          • thoracic spine is most common site of bony metastasis
        • 2nd most common site of mets is proximal femur
          • proximal femur is most common site of fracture secondary to metastatic bone lesions
            • 65% nonunion rate
          • 50% in femoral neck, 20% pertrochanteric, 30% subtrochanteric
  • Etiology
    • Pathophysiology
      • mechanism of bone destruction (osteolysis)
        • osteolytic bone lesions are caused by tumor induced activation of osteoclasts
          • occurs through the RANK, RANK ligand (RANKL), osteoprotegrin pathway
          • PTHrP positive breast cancer cells activate osteoblastic RANKL production
        • osteoblastic bone metastases are due to tumor-secreted endothelin 1
    • Associated conditions
      • metastatic hypercalcemia
        • a medical emergency
        • symptoms include
          • confusion
          • muscle weakness
          • polyuria & polydipsia
          • nausea/vomiting
          • dehydration
        • treatment
          • hydration (volume expansion)
          • loop diuretics
          • bisphosphonates
  • Principles of metastasis
    • Mechanism of metastasis
      • tumor cell intravasation
        • E cadherin cell adhesion molecule (on tumor cells) modulates release from primary tumor focus into bloodstream
      • avoidance of immune surveillance
      • target tissue localization
        • attaches to target organ endothelial layer via integrin cell adhesion molecule (expressed on tumor cells)
      • extravasation into the target tissue
      • induction of angiogenesis
        • via vascular endothelial growth factor (VEGF) expression
      • genomic instability
      • decreased apoptosis
    • Vascular spread
      • Batson's vertebral plexus
        • valveless venous plexus of the spine that provides a route of metastasis from organs to axial structure including vertebral bodies, pelvis, skull, and proximal limb girdles
    • Mechanism of bone lysis
      • oncogenic cell releases cytokines IL-6, IL-11, PTHrP, TGF-beta
      • PTHrP and TGF-beta activate osteoblasts
      • osteoblasts secrete RANKL, that binds to RANK on osteoclasts and activates osteoclasts
    • Mechanism of bone sclerosis (prostate and breast mets)
      • prostate cancer cells secrete endothelin 1 (ET-1)
      • ET-1 binds to endothelin A receptor (ETAR) on osteoblasts and stimulates osteoblasts
      • ET-1 decreasesWNT suppressor DKK-1
        • activates WNT pathway, increasing osteoblast activity
  • Classification
    • Tokuhashi score specific to metastatic disease to spine
      • prognostic score based on 6 elements: general condition, extraspinal bony metastasis, number of vertebral bodies with metastasis, visceral metastasis, primary tumor, neurologic compromise
      • score of 0-8: <6 months; 9-12 > 6 months, 12-15 >1 year
  • Symptoms
    • Symptoms
      • pain
        • axial night pain
          • may be mechanical pain due to bone destruction or tumorigenic pain which often occurs at night
        • metastatic hypercalcemia
    • Physical exam
      • neurologic deficits
        • caused by compression of the spinal cord with metastatic disease to the spine
      • hyper-reflexia
  • Evaluation
    • Workup for older patient with single bone lesion and unknown primary includes
      • imaging
        • AP and lateral of spine in region of pain
        • CT of chest / abdomen / pelvis
        • technetium bone scan to detect extent of disease
          • myeloma and thyroid carcinoma are often cold on bone scan - evaluate with a skeletal survery
      • labs
        • CBC with differential
        • ESR
        • basic metabolic panel
        • LFTs, Ca, Phos, alkaline phosphatase
        • serum and urine immunoelectrophoresis (SPEP, UPEP)
      • biopsy
        • in patients where a primary carcinoma is not identified, obtaining a biopsy is necessary to rule out a primary bone lesion
          • should not treat a bone lesion without tissue diagnosis of the lesion
        • metastatic adenocarcinoma not identified by CT of the chest, abdomen, and pelvis is most likely from a small lung primary tumor
    • See table of evaluation algorithms based on patient factors
  • Imaging
    • Radiographic
      • recommended views
        • AP and lateral of involved area off spine
      • findings
        • purely lytic or mixed lytic/blastic lesions
          • lung, thyroid, and renal are primarily lytic
          • 60% of breast CA is blastic
          • 90% of prostate CA is blastic
    • CT scan
      • helpful to identify metastatic lesions to the spine
    • MRI
      • useful to show neurologic compromise of the spine
  • Studies
    • Histology
      • characteristic findings
        • epithelial cells in clumps or glands in a fibrous stroma
      • immunohistochemical stains positive
        • Keratin
        • CK7 (breast and lung cancer)
        • TTF1 (lung cancer)
  • Treatment 
    • General considerations
      • NOMS framework: neurologic, oncologic, mechanical instability, systemic illness
        • neurologic: measure of epidural spinal cord compression (ESCC)
          • 0-1 low grade, 2-3 high grade
        • oncologic: responsiveness to radiation
        • mechanical instability: spinal instability neoplastic score (SINS)
          • SINS: 0-6 no surgical consultation required, 7-18 surgical consultation advisable
        • systemic illness: formulation of prognosis from disease burden, medical comorbidities, functional status
    • Nonoperative
      • palliative care
        • indications
          • life expectancy of < 6 months
            • Tokuhashi scoring system can be used to determine life expectancy
      • radiation alone
        • indications
          • may be indicated in patients who are not surgical candidate
          • no signs of neural compression, neurologic deficit, or instability
    • Operative
      • neurologic decompression, spinal stabilization, and postoperative radiation
        • indications
          • metastatic lesions to spine with neurologic deficits in patients with life expectancy of > 6 months
        • technique
          • preoperative embolization indicated in metastatic renal and thyroid CA to spine
  • Complications
    • Recurrence
    • Hardware failure and spinal instability
    • Nonunion of fracture
    • Wound complications
      • Immediate soft tissue reconstruction has a lower complication rate than delayed reconstruction in patients undergoing revision metastatic spine tumor surgery
  • Prognosis
    • Median survival in patients with metastatic bone disease
      • thyroid: 48 months
      • prostate: 40 months
      • breast: 24 months
      • kidney: variable depending on medical condition but may be as short as 6 months
      • lung: 6 months
    • Tokuhashi score (see classification section)
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