Long bone skeletal metastases are common in the United States, with more than 280,000 new cases every year. Most of these will be managed by the on-call orthopedic surgeon. A practical primer is offered for the evaluation and surgical management for the practicing orthopedist, including questions to ask during the history, pertinent physical examination findings, appropriate imaging requests, proper laboratory work, and biopsy options. Finally, 7 scenarios are presented to encompass most situations a practicing orthopedic surgeon will encounter, and guidelines for treatment and referral are offered.
Key points
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A thorough evaluation should be conducted to confirm metastatic disease before definitive fixation.
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Placement of the biopsy is crucial to prevent further morbidity.
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Prophylactic fixation (long nails) for impending fractures is preferred.
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Cemented arthroplasty options for periarticular pathologic fractures and long nails for other kinds of fractures including peritrochanteric are preferred.
Introduction
Treatment of skeletal metastases is a significant part of cancer care in the United States. The estimated prevalence of metastatic bone disease in the United States is at least 280,000 per year and is expected to increase as medical management improves overall survivorship. Postmortem analysis shows that around 70% of all patients with breast and prostate cancer have skeletal metastases, and it involves between 35% and 42% of patients with lung, thyroid, and renal cancer. The economic costs of treatment of metastatic bone disease in the United States per year are an estimated $12.6 billion, which is 17% of the total annual cost of cancer treatments.
The purpose of this article is to review the presentation, workup, and treatment options for metastatic disease to the long bones. Seven scenarios are presented to help the practicing orthopedist identify and treat metabolic bone disease safely.
Introduction
Treatment of skeletal metastases is a significant part of cancer care in the United States. The estimated prevalence of metastatic bone disease in the United States is at least 280,000 per year and is expected to increase as medical management improves overall survivorship. Postmortem analysis shows that around 70% of all patients with breast and prostate cancer have skeletal metastases, and it involves between 35% and 42% of patients with lung, thyroid, and renal cancer. The economic costs of treatment of metastatic bone disease in the United States per year are an estimated $12.6 billion, which is 17% of the total annual cost of cancer treatments.
The purpose of this article is to review the presentation, workup, and treatment options for metastatic disease to the long bones. Seven scenarios are presented to help the practicing orthopedist identify and treat metabolic bone disease safely.
Presentation
The typical patient will present with a history of a primary carcinoma and bony pain. Occasionally (about 15% of the time), the patient will present with no known primary. The bone pain is typically described as a “gnawing, tooth-achy” pain, or “night” pain. Pain with weight-bearing or sharp pain is concerning for impending pathologic fracture. The most common locations for metastatic disease include the spine, pelvic girdle, shoulder girdle, and distal femur. Metastasis distal to the knee and elbow is rare except for lung cancer.
A thorough history and physical examination are mandatory, including past medical history, smoking history, exposure to carcinogens and radiation, and a full review of symptoms including constitutional symptoms ( Table 1 ).
| Review of System | Possible Malignancy |
|---|---|
| Fevers, sweats, chills, weight loss | Lymphoma |
| Shortness of breath, pleuritic pain, hemoptysis | Lung |
| Voiding difficulty | Prostate |
| Hematuria | Renal |
| Breast discharge or mass | Breast |
| Rectal bleeding, anemia | Colon |
Physical examination should include an examination of the limb, looking for causes of pain other than cancer, as well as goiter examination, lymph node examination, auscultation of the lungs, breast examination, and digital rectal examination ( Table 2 ).
| Physical Examination | Possible Malignancy |
|---|---|
| Jaundice | Liver |
| Neck nodules | Thyroid |
| Axillary nodules, breast lump, or discharge | Breast |
| Dull auscultation of the lungs | Lung |
| Splenomegaly | Lymphoma |
| Positive digital rectal examination | Prostate |
Laboratory workup
Standard laboratory workup for patients without a known primary include CBC with Diff, CMP, U/A, ESR/CRP, PSA, SPEP/UPEP, PTH ( Table 3 ).
| Lab | Possible Malignancy |
|---|---|
| CBC with Diff | Multiple myeloma, leukemias |
| CMP: Ca/Alk Phos | Amount of bony involvement, prognosis |
| U/A | Renal from hematuria |
| ESR/CRP | Inflammation from infection, tumor burden |
| PSA | Prostate |
| SPEP/UPEP | Multiple myeloma |
| PTH | Metabolic bone disease |
Imaging workup
Good radiographs, focused on the tumor in orthogonal planes, are required for proper assessment of the lesion. Axial imaging (computed tomography [CT] or magnetic resonance imaging scan) can be helpful in determining the amount of bony destruction, extent of the tumor, risk of fracture, and choice of implant. A whole body bone scan is useful for determining other sites of metastatic disease. If multiple myeloma is known or suspected, a skeletal survey is needed because many of the lesions will not be osteoblastic.
If the primary is unknown, radiographs, CT scan of the chest, abdomen, and pelvis, and a whole body bone scan are recommended. Approximately 85% of primary tumors can be identified in this manner. Mammography for women and thyroid ultrasound can be helpful if the physical examination findings are supportive ( Table 4 ).
| Imaging | Use |
|---|---|
| X-rays | Screening, surgical planning |
| CT or magnetic resonance imaging of bone | Risk of fracture, extent of disease, choice of implant |
| Whole body bone scan | Screen for other sites of bony metastatic disease |
| Skeletal survey | Screen for multiple myeloma |
| CT chest/abdomen/pelvis | Look for solid organ primary carcinoma |
| Mammography | Screen for breast cancer primary (if examination is suspicious) |
| Thyroid ultrasound | Screen for thyroid cancer primary (if examination is suspicious) |
Pathologic workup
A biopsy is recommended if the primary is unknown, or if it is a solitary lesion. This biopsy is to ensure that the tumor is not a primary bone sarcoma or that there is not a secondary primary. The biopsy can be performed using a core needle technique (with or without interventional radiology) or an open procedure ( Table 5 ). If surgical fixation is already planned, then a separate, well-planned open biopsy with frozen section immediately before the fixation should be considered. The case should not proceed until the pathology report is returned, confirming metastatic disease. If the frozen pathology specimen is inconclusive, then the case should be aborted until the final pathology report is returned.
Q: Is sending the reamings from the nailing ok for the biopsy?
A: Sending reamings is not recommended for 2 reasons. First, the quality of the tissue has been compromised by the destructive shearing forces of the reamer, leading to a less accurate result. Second, the entire femur is now contaminated by tumor, which may complicate reconstructive options if the tumor was not a carcinoma. A separate open biopsy and waiting for the results before taking the steps for fixation (incision extension, reaming) are recommended.
| Biopsy Type | Advantages | Disadvantages |
|---|---|---|
| Open (1–3 cm incision) | Most tissue, most accurate | Most contamination from size of incision |
| Core needle (10–14 g) | Maintains architecture of tissue Little contamination | Less accurate due to less tissue (80%) |
| Fine needle aspirate (24 g) | Little contamination | Least accurate due to loss of architecture of tissue |
It is recommended that the biopsy be performed at institutions that have the capability to treat the definitive disease because a poorly placed biopsy can significantly affect the morbidity of subsequent procedures, affecting the amount of soft tissue and bony resection, function after surgery, and recurrence. Poorly placed CT-guided needle biopsies can also contaminate tissue planes, necessitating a change in the subsequent surgery and morbidity.
Q: What are the keys to a well-placed biopsy?
A:
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Place the biopsy tract in-line with the planned incision line from the definitive surgery
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Use longitudinal incisions (incisions parallel to the underlying compartment)
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Go through soft tissue compartments, not around them, to contaminate less tissue
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Undermine as little tissue as possible
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Get meticulous hemostasis, or place a drain to prevent hematoma and spread of tumor
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Get a frozen section to confirm pathologic tissue on the specimen
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Treatments can vary substantially based on the histology. Some primary tumor-specific information is provided in Table 6 .
| Radiosensitive? | Chemosensitive? | Hormone Sensitive | Bloody? | Fracture Heal Rate | Metastatectomy? | |
|---|---|---|---|---|---|---|
| Breast | Yes | Yes | Yes | No | 37% | No |
| Kidney | Only at higher doses | Yes | No | Yes, embolize before open procedures | 44% | Yes |
| Lung | Yes | Yes | No | No | 0 | No |
| Prostate | Yes | Yes | Yes | No | ? | No |
| Thyroid | Yes, use radioiodine therapy | Yes | No | Yes, embolize before open procedures | ? | Yes |
| Multiple myeloma | Yes | Yes | No | Possibly, consider embolize before open procedures | 67% | No |
Treatments
Treatments for bony metastasis depend on the clinical presentation and tumor type. If the patient is asymptomatic, then observation with repeat radiographs in 3 to 4 months may be all that is needed. Use of a bisphosphonate or a RANK L inhibitor should be considered to reduce skeletally related events or fractures. If the patient is symptomatic, but there is no risk for pathologic fracture, then radiation therapy may be helpful for palliation of the symptoms. Patients with multiple lesions may be candidates for radiopharmaceutical treatments.
ASTRO Guidelines for Palliative Skeletal Metastasis
30 Gy in 10 fractions OR 8 Gy in 1 fraction
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