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
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

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

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 of Metastatic Lesions to Spine

Nonoperative
- palliative care
  - indications
    - life expectancy of < 6 months
      - Takuhashi 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

Complications

Recurrance
Hardware failure and spinal instability
Nonunion of fracture

Current Approaches to Metastatic Bone Disease Anna Kulidjian, M.D. (COA 2017, 3.1)

En Bloc Resection of Tumors of the Spine