Metastatic Disease of Spine

Topic updated on 08/25/16 11:41am
  • Metastatic cancer is the most common reason for a destructive bone lesion in adults 
    • carcinomas that commonly spread to bone include
      • breast
      • lung
      • thyroid
      • renal
      • prostate
  • Epidemiology
    • incidence
      • bone is the third 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
    • 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)
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 CA to spine   
  • Recurrance
  • Hardware failure and spinal instability
  • Nonunion of fracture


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Qbank (16 Questions)

(OBQ12.124) A 68-year-old male presents to the emergency room with neck pain and progressive weakness to the point that he is unable to walk. Prior to this event he was in good health and active. On physical exam he is an ASIA C. Radiographs, computed tomography, and an MRI are show in Figure A,B, and C respectively. A CT of the chest, abdomen, and pelvis shows a single resectable lesion in the rectum consistent with a primary malignancy. Sagittal images of the spine show a single metastatic lesion in the thoracic spine, but no signs of thoracic canal compromise. He has no other metastatic bone lesions. What is the best treatment for this patient? Topic Review Topic
FIGURES: A   B   C      

1. Surgical decompression and stabilization followed by radiation
2. Radiation followed by surgical decompression and fusion
3. Radiation alone
4. Chemotherapy alone
5. Palliative measures

(OBQ12.162) A 62-year-old male patient presents with severe lower back pain radiating to his right lower abdomen and right leg. He previously underwent a right nephrectomy for renal cell carcinoma. On physical exam, he has weakness with right knee extension which is affecting his ability to ambulate. An MRI is performed and is shown in Figures A and B. Staging studies determine this to be an isolated metastatic lesion. What is the next best step in this patient's treatment? Topic Review Topic
FIGURES: A   B        

1. Chemotherapy alone
2. Radiation alone
3. Vertebroplasty
4. Embolization, surgical decompression and stabilization followed by radiation
5. Surgical decompression and stabilization followed by radiation

(OBQ09.51) A 59-year-old female with a history of biopsy proven metastatic renal cell carcinoma presents with a thoracic spine lesion consistent with renal cell carcinoma. She has lower extremity weakness and sustained clonus bilaterally. What is the most appropriate management prior to surgery? Topic Review Topic

1. Blood cultures
2. High dose IV methylprednisone
3. Arterial embolization
4. CT guided cryotherapy
5. Radiation therapy

(OBQ09.83) You are caring for a 63-year-old female with metastatic breast cancer to the lumbar spine. Her neurological examination shows significant weakness in leg function and she is having difficulty ambulating. Imaging shows significant neural element compression by the tumor and complete erosion of the L1 vertebrae. She has no other sites of metastatic disease and is otherwise healthy. What treatment option do you recommend to best maintain her function? Topic Review Topic

1. Palliative therapy
2. Complete neural element decompression
3. Complete neural element decompression with instrumentation to stabilize the spine
4. Complete neural element decompression, instrumentation, and postoperative chemotherapy
5. Complete neural element decompression, instrumentation, and postoperative radiotherapy

(OBQ08.66) A 47-year-old female, otherwise in good general condition, has intractable back pain from metastatic breast cancer isolated to her spine. She has failed progressive multi-agent chemotherapy and hormone therapy. Her exam is normal except for slight sensory dysesthesia, hyperreflexic patellar tendons, and mild gait instability which she reports has been worsening. Cervical, thoracic, and lumbar MRI show an isolated metastatic lesion involving the T9 vertebral body with moderate cord compression of the ventral spinal cord. At this stage what is the best treatment? Topic Review Topic

1. Change chemotherapy protocol to Cyclophosphamide, Hydroxydanurubicin, Oncovin, Prednisone
2. Posterior spinal decompression after vertebral body kyphoplasty
3. Thoracic corpectomy, instrumented spinal fusion, and postoperative radiotherapy
4. Radiation therapy
5. Palliative care unit

(OBQ08.204) A 67-year-old retired male custodian complains of progressively worsening low back pain over the past 6 months. He has not seen a doctor in the past 15 years. He admits to a 40 pack year smoking history, fatigue, and an unintentional 15 pound weight loss over the past year. A radiograph of the pelvis is provided in Figure A. Which of the following would most likely confirm the diagnosis? Topic Review Topic
FIGURES: A          

1. Urine immunoelectrophoresis (UPEP)
2. Thyroid biopsy
3. CBC and blood smear
4. Prostate biopsy
5. Renal ultrasound

(OBQ05.207) A 59-year-old female presents with a metastatic spinal tumor and has a lytic lesion in the T12 vertebral body. The process of bone resorption in her lytic lesion is mediated by Topic Review Topic

1. Direct resorption of bone by tumor cells
2. Neoangiogenesis of the vertebral body
3. Macrophage-mediated bony destruction
4. Tumor induced activation of osteoclasts
5. Necrosis of the vertebral body

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