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Bony and Spinal Metastasis

Basics

Description

- 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)

- Types of bone metastasis - Osteolytic-thyroid, non-small cell lung, kidney, multiple myeloma - Osteoblastic-prostate, small cell lung - Mixed-breast, cervical, ovarian, testicular

- Prevention of primary tumor/early detection - Timely mammogram evaluations - Cervical Pap smears - Prostate-specific antigen (PSA) per guidelines-strong family history - Colonoscopy

- 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]

- Analgesics - NSAIDs (1)[A] - Opioids - Triple therapy-extended release, immediate acting, rapid onset (1)[A]

- 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

- 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

- Hormonal therapy-only indicated in certain types of cancer-breast and prostate specifically (1)[A]. - Chemotherapy - Radiotherapy - Radiopharmaceuticals - Intrathecal analgesics-per anesthesia

  • 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 understoodApproximately 1.2 million new cancer diagnoses in the United States each yearApproximately 300,000 total cases of metastatic bone disease in the U.S. population in 2008 (3,4)

Etiology and Pathophysiology

  • Types of bone metastasisOsteolytic-thyroid, non-small cell lung, kidney, multiple myelomaOsteoblastic-prostate, small cell lungMixed-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 smearsProstate-specific antigen (PSA) per guidelines-strong family historyColonoscopy

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 historySigns 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 specificBone scanComputed tomography (CT) scan of chest, abdomen, pelvis to evaluate primaryMagetic 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 siteTissue 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

  • AnalgesicsNSAIDs (1)[A]OpioidsTriple 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 compressionMethylprednisolone-32 mg/dayPrednisone-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 boneDenosumab-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 weeksPamidronate-90 mg IV monthlyIbandronate-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 compressionGabapentin-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/hospiceAssess 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
  • RadiotherapyRadiopharmaceuticalsIntrathecal 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].
  • VertebroplastyKyphoplastyDecompression and stabilizationTumor resectionEmbolizationThermoablation

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 deteriorationMechanical instability of the spineFractureTo 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.