Basics
Description
- The skeleton is one of the most common sites for metastatic cancer.
- Bone metastasis can cause significant morbidity including pain, pathologic fractures, spinal cord compression, and hypercalcemia.
- 80% of bony metastasis are due to breast, prostate, and lung cancers (1).
Epidemiology
Incidence
- Breast cancer-73% bony metastasis
- Prostate-68%
- Thyroid-42%
- Lung-36%
- Renal-35%
- Melanoma-35% (2)
Prevalence
- Not well understood
- Approximately 1.2 million new cancer diagnoses in the United States each year
- Approximately 300,000 total cases of metastatic bone disease in the U.S. population in 2008 (3,4)
Etiology and Pathophysiology
- Types of bone metastasis
- Osteolytic-thyroid, non-small cell lung, kidney, multiple myeloma
- Osteoblastic-prostate, small cell lung
- Mixed-breast, cervical, ovarian, testicular
- Bone-specifically the axial skeleton-is a common site for metastasis due to high blood flow in the red marrow.
- Tumor cells exhibit adhesive molecules that allow them to bind stromal cells in the bone marrow.
- Tumor cells produce factors that stimulate osteoblastic and/or osteoclastic activity leading to disruption in bone remodeling (2)[A].
Genetics
- Studies are ongoing in identifying specific genes involved in bony metastasis.
- 5-10% of all cancers are hereditary.
- Most common type is hereditary breast and ovarian cancer syndrome caused by mutations in BRCA1 or BRCA2 (4).
Risk Factors
- Advanced disease
- Late presentation to care
- Large tumor size
- Poorly differentiated tumor
- Breast cancer is the most likely culprit for bony metastasis in the United States.
General Prevention
- Prevention of primary tumor/early detection
- Timely mammogram evaluations
- Cervical Pap smears
- Prostate-specific antigen (PSA) per guidelines-strong family history
- Colonoscopy
Commonly Associated Conditions
- Bone pain
- Pathologic fractures
- Hypercalcemia
- Nerve compression
- Spinal cord compression
- Cauda equina syndrome
Diagnosis
History
- Previous cancer diagnosis or treatment
- Occupational and exposure history
- Signs and symptoms specific to organs to help identify primary site
Physical Exam
- Differentiating between bone and joint pain-metastasis is more likely to cause bone pain in the absence of nearby joint pain.
- Examine the primary site.
Differential Diagnosis
- Primary bone malignancy
- Paget disease
- Traumatic fracture
- Degenerative joint disease (DJD)-spine
- Osteoarthritis
- Osteoporosis
Diagnostic Tests & Interpretation
Initial Tests (lab, imaging)
- Lab-complete blood count (CBC), creatinine, calcium, alkaline phosphatase, PSA, immunoelectrophoresis
- Imaging-plain x-ray initial test-most specific
- Bone scan
- Computed tomography (CT) scan of chest, abdomen, pelvis to evaluate primary
- Magetic resonance imaging (MRI)-extent of bony spread, vertebral integrity, neurologic deficit (5)[C]
Follow-up tests & special considerations
- Collaborate with oncologist for regular laboratory and imaging follow-up.
- CBC and electrolyte monitoring (weekly to monthly dependent on treatment course) (5)
- Consult hospice-life expectancy <6 months (6)[C]
Diagnostic Procedures/Other
- Biopsy needed to establish primary tumor site
- Tissue diagnosis also key in evaluation of hormonal and immunohistochemical components (7)[C]
Treatment
General Measures
- Treatment depends on many factors including histology, site of disease, extent of epidural disease, extent of metastasis, and neurologic compromise from metastasis (1,6)[C].
- A multidisciplinary approach is essential.
Medication
First Line
Primary cancer treatment
- Analgesics
- NSAIDs (1)[A]
- Opioids
- Triple therapy-extended release, immediate acting, rapid onset (1)[A]
Second Line
- Steroids-indicated for analgesic effect as well as acute spinal cord compression (1)[A].
- Dexamethasone(preferred)-12-20 mg/day for pain; 16-96 mg/day for spinal cord compression
- Methylprednisolone-32 mg/day
- Prednisone-10-50 mg/day for pain; 40-80 mg/day for spinal cord compression
- Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor-inhibition of osteoclast activity in bone
- Denosumab-120 mg SQ every 4 weeks
- Bisphosphonates-inhibition of osteoclasts shown to reduce skeletal complications and pain from metastasis. Only medication shown to improve hypercalcemia (1,2)[A].
- Zoledronic acid intravenous (IV) (preferred)-4 mg IV every 3-4 weeks
- Pamidronate-90 mg IV monthly
- Ibandronate-6 mg IV every 3-4 weeks
- Antiepileptics-relief of neuropathic pain (1)[B].
- Pregabalin-75 PO b.i.d.-decrease in neuropathic pain-indicated in spinal compression
- Gabapentin-300-600 t.i.d.
- Topiramate-25 mg/day b.i.d.-indicated in neuropathic pain
Issues for Referral
- Pain management
- Medical oncology
- Radiation oncology
- Palliative care/hospice
- Assess risk of fracture and obtain orthopedics and spine referrals.
- Assess patient's psychiatric wellness-obtain referral as indicated.
- Mobility assessment-physical therapy (PT), home health, occupational therapy (OT), assistive devices
Additional Therapies
- Hormonal therapy-only indicated in certain types of cancer-breast and prostate specifically (1)[A].
- Chemotherapy
- Radiotherapy
- Radiopharmaceuticals
- Intrathecal analgesics-per anesthesia
Surgery/Other Procedures
- Indications for surgery include intractable pain, onset of neurologic deficits, mechanical instability of the spine, failure of a previous therapy, or tumor removal (7)[C].
- Vertebroplasty
- Kyphoplasty
- Decompression and stabilization
- Tumor resection
- Embolization
- Thermoablation
Complementary & Alternative Therapies
- Acupuncture
- Tai chi, yoga, heat, cold
- Behavioral medicine approaches, cognitive behavioral therapies
- Meditation, hypnosis (1)[C]
Inpatient Considerations
Admission Criteria/Initial Stabilization
- Electrocardiogram (ECG) changes-hypercalcemia
- Intractable pain
- Neurologic deterioration
- Mechanical instability of the spine
- Fracture
- To obtain diagnostic biopsy
IV Fluids
Only as needed for comorbid conditions, dehydration, renal failure, hypercalcemia
Nursing
- Bed rest until orthopedic physician gives clearance
- Depression and anxiety are common in cancer patients.
- Notify physicians with any change in neurologic status.
Discharge Criteria
- Pain controlled
- Safe mobilization
- Return of calcium to a safe level
- Long-term cancer care team established
Ongoing Care
Follow-up Recommendations
- Regular follow-up with oncology and other members of patient cancer care team
- Physical therapy
- Assistive devices to help reduce fracture risk
Patient Monitoring
Regular labs and scans as specified by oncologist based on treatment and underlying malignancy
Diet
Regular as tolerated
Patient Education
- http://www.cancer.org
- http://www.nih.gov
Prognosis
Once bony metastasis has been diagnosed, the median survival rates are as follows:
- 12 months-breast cancer
- 6 months-prostate cancer
- 3 months-lung cancer
Complications
- Neurologic compromise
- Debilitating pain
- Immobility
- Depression/anxiety
References
1.Smith HS, Mohsin I. Painful boney metastases. Korean J Pain. 2013;26(3):223-241.
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2.Suva LJ, Washam C, Nicholas R, et al. Bone metastasis: mechanisms and therapeutic opportunities. Nat Rev Endocrinol. 2011;7(4):208-218.
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3.Li S, Peng Y, Weinhandl E, et al. Estimated number of prevalent cases of metastatic bone disease in the US adult population. Clin Epidemiol. 2012;4:87-93.
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4.Yamashiro H, Takada M, Nakatani E, et al. Prevalence and risk factors of bone metastasis and skeletal related events in patients with primary breast cancer in Japan. Int J Clin Oncol. 2013:1-11.
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5.Riccio AI, Wodajo FM, Malawer M. Metastatic carcinoma of the long bones. Am Fam Physician. 2007;76(10):1489-1494.
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6.Lutz ST, Chang EL, Galanopoulos N, et al. ACR Appropriateness Criteria ® spinal bone metastases. J Palliat Med. 2013;16(1):9-19.
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7.Gasbarrini A, Boriani S, Capanna R, et al. Management of patients with metastasis to the vertebrae: recommendations from the Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group. Exp Rev Anticancer Ther. 2014;14:143-150.
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Codes
ICD09
- 198.5 Secondary malignant neoplasm of bone and bone marrow
ICD10
- C79.51 Secondary malignant neoplasm of bone
SNOMED
- 94222008 Secondary malignant neoplasm of bone (disorder)
- 94602001 Secondary malignant neoplasm of vertebral column (disorder)
- 285618001 Metastasis to bone of unknown primary
Clinical Pearls
- Metastatic cancer should be included in the differential diagnosis of unexplained musculoskeletal pain in adults.
- Bone and spinal metastasis requires a multidisciplinary treatment approach.
- Mainstay of pain treatment is opioid analgesics.
- Bisphosphonate therapy should be started when bone metastasis is diagnosed.
- Treatment of bony and spinal metastasis is essential in decreasing long-term disability and increasing quality of life-no evidence has shown an increase in life expectancy.