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)
  • locations
    • 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
• 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 
• 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) 
• Associated conditions
  • metastatic hypercalcemia
    • a medical emergency
    • symptoms include
      • confusion
      • muscle weakness
      • polyuria & polydipsia
      • nausea/vomiting
      • dehydration
    • treatment
      • hydration (volume expansion)
      • loop diuretics
      • bisphosphonates

• 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

• 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
  • 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

• 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  

• 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

• 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)

• 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
• 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   

• Recurrence
• Hardware failure and spinal instability
• Nonunion of fracture