Bone metastases are defined as oncologic lesions within bone that occur distant from the primary site of cancer. Bone metastases occur at advanced stages of cancer and are one of the most common sites of tumor spread away from the primary location.
Bone metastases are extremely common in cancer. Current estimates project a prevalence of bone metastases in over 280,000 patients in the United States.1 Approximately 350,000 individuals are estimated to expire with bone metastases annually.2 Besides lung and liver lesions, metastases to the bone are the third most common location of lesions distant from the primary tumor.3 Cancers of the breast, prostate, lung, kidney and thyroid, in addition to multiple myeloma, typically spread to bone.1,4-7
Risk factors for developing bone metastases include the presence of an osteophillic tumor that is not adequately controlled or treated. Bone metastases can occur in any location but are seen typically in the spine, pelvis, rib cage, and long bones such as the femur.7-9 In breast cancer, tumor subtype in addition to size, stage, grade and nodal spread are risk factors for the development of bone metastases, while other variables such as age and body mass index are suggestive of risk but controversial.9-10 Prostate-specific antigen levels and rates of change have also been investigated as potential risk factors for the development of bone metastases in prostate cancer.11
Etiology and Pathophysiology
Bone metastases result from cancer cell seeding and subsequent growth at a site distant from the primary tumor.5 Growth at sites distant from the primary tumor site is dependent on a number of biochemical factors.5 The fertile microenvironment within bone encourages tumors to spread to this location and grow successfully.5,12
Metastases usually occur in the axial skeleton, which has a higher percentage of red marrow.4 Osteoclasts and osteoblasts are activated in the setting of bone metastases and increase a number of biochemical factors to enhance tumor cell growth.5,12 Metastases can be classified as osteolytic, osteoblastic, or mixed.12
Bone metastases can present in a variety of ways. Bone metastases may be asymptomatic and detected only on routine surveillance studies.3 Pain is a common presentation of bone metastases.3,12 Pain associated with bone metastases can occur from direct bone involvement resulting in localized inflammation and biologic pain.4 Pathologic fracture and spine cord compromise are also potential side effects of spinal metastases.3,4,6,9,12
Skeletal related events occur as a complication of bone metastases.3-6,12 Common skeletal related events include pain, pathologic fracture, spinal cord compromise and hypercalcemia resulting in an increased need for radiation therapy or surgery.3-6,9,12 These complications can cause increased morbidity and mortality.5 The prognosis of the individual patient with bone metastases varies depending on the type of primary tumor.4
2. ESSENTIALS OF ASSESSMENT
Individuals with bone metastases may be asymptomatic or may present with pain or neurologic symptoms.3-6,9,12 Patients may also present with fracture related pain as the initial symptom of metastases. Spinal metastases often present with back pain prior to the onset of neurologic impairments.4 Biologic tumor pain is usually local to the site of involvement and occurs as a result of inflammation from tumor growth within bone.3-4 Biologic tumor pain is often worse at night and with lying supine.3-4 Mechanical pain is worsened by increased axial loading of the affected bone with activities such as walking or Valsava maneuvers.4 Metastases can also cause mechanical instability within the bony spine with flexion and extension. Pain can be intermittent or constant and can be sharp and severe in quality.3 Patients may also present with pain in nearby structures due to altered biomechanics.13-14
In cases of changes in neurologic function as the result of bone metastases, patients can experience symptoms such as bowel or bladder impairment, weakness or sensory alterations.4 Metastases can also result in neurologic symptoms and signs such as cranial nerve palsies and headache if they occur at the base of the skull.4
Physical examination can demonstrate erythema, swelling, or localized tenderness in addition to reduced range of motion. Caution is advised when performing manual testing in patients with suspected long bone metastases or pathologic fractures.15 Discomfort with axial loading suggests mechanical instability or fracture.4 An abnormal neurologic exam may suggest radiculopathy or myelopathy with changes such as weakness, altered pin prick or light touch sensation, reduced proprioception, hyper or hyporeflexia, clonus or a positive Babinski sign.4
Patients should be individually evaluated for independence with activities of daily living, transfers, mobility, and balance in the setting of bone metastases. The home and social supportive environment should be assessed as well to maximize patient mobility.
In general, studies investigating different levels of bone markers to detect and monitor bone metastases are not recommended.16
Plain radiographs are poor screening tests for metastatic bone lesions as a result of very low sensitivity.13-14 Bone scans are sensitive for bone metastases but are nonspecific because they detect active bone remodeling and turnover which can occur in a number of conditions.3,13-14 However, bone scans may not be positive in the presence of aggressive metastases while diffuse uptake may be seen in diffuse skeletal disease and present as a false negative study.13-14 Computer tomography (CT) and magnetic resonance imaging (MRI) both detect bone marrow changes which can signify bone metastases.3,13-14 Bone metastases are areas within bone of low intensity on T1-weighted MRIs while on T2-weighted images bone metastases demonstrate high intensity.13-14
Supplemental assessment tools
There are a plethora of pain and function assessment scales that can be used for someone with bone metastases. Assessment of quality of life with regards to pain and psychosocial well-being is essential, and there are a number of instruments available for this task.17 Commonly used scales in this population include the Brief Pain Inventory, the functional assessment of cancer therapy-general (FACT-G), the Karnofsky Performance Scale (KPS) and the Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status.18-19
Early predictions of outcomes
The presence of bone metastases themselves can increase mortality and lesions that occupy more than 50% of the cortical bone are particularly worrisome.5 Fractures and spinal cord compromise from bone metastases can reduce quality of life and mobility.12 Osteolytic tumors are more likely to fracture than osteoblastic lesions.6 The Mirels scoring system can be used to predict the risk of fracture of long bones based on pain, size, location and nature of the lesion.20 The Spinal Instability Neoplastic Score reliably evaluates tumor-related spinal instability.21
In the evaluation of a cancer patient with bone metastases, reducing the potential for falls is of the utmost importance to avoid a pathologic fracture or spinal cord compromise. Patients should be evaluated for individualized needs of durable medical equipment, bracing, assistive devices and home modifications to improve independence and reduce the potential for falls.
Social role and social support system
The individual family and social support structures influence the functional goals of patients with bone metastases. Understanding the individual patient’s overall prognosis assists with appropriate and realistic goal formation in the setting of impairments and disability.
Physiatrists hold a unique role within the medical team of the oncology patient with bone metastases. Forming realistic functional goals in regards to specific impairments from bone metastases allows patients and families to plan and make modifications where necessary.
3. REHABILITATION MANAGEMENT AND TREATMENTS
Impairment and Treatment Overview
Bone metastases can be treated in a number of ways. Some metastases may be treated conservatively and watched over time, addressing pain management needs with acetaminophen and nonsteroidal antiinflammatory drugs and escalating pain medications as needed.3,5,22 Other metastases may be treated with radiation, chemotherapy, antihormonal therapy, bisphosphonates, denosumab, and prophylactic or reconstructive repair.3,5,7,23 Restoring function with return to full weight bearing is extremely important in this population.3
Generally, the rehabilitation program of an individual with bone metastases must be unique based on the location and level of involvement of other lesions. The location and total amount of bone metastases does not alter functional ability; rather, pain and neurologic impairment from bone metastases reduce mobility.8 Historically, patients were advised to maintain bedrest, but reducing activity does not necessarily prevent fracture.15,24 Only pain-limited active range of motion should be performed, and caution should be advised with manual muscle testing.15 Passive or active-assisted range of motion is not advised.15 Patients with stable spinal metastases did not experience any adverse effects but did experience reduced pain after undergoing an isometric resistance training program of the paravertebral muscles during ongoing radiation therapy.25 In one study, patients who performed eccentric and concentric resistive exercises in areas without bone metastases did not experience any adverse events.26 The same study demonstrated that resistive exercises in non-metastatically involved areas improved strength, aerobic capacity and ambulation.26
Lesions of the hip and pelvis can be managed with prophylactic surgical fixation or reconstructive repair after a fracture.15,23 Post-operative patients are often placed on standard hip precautions with early mobilization and weight-bearing as tolerated.15 Upper extremity metastases can be treated conservatively with a sling or surgery with early active range of motion on a case by case basis.15 For spinal metastases, systematic treatment is often implemented unless there is spinal instability or spinal cord compromise with a focus on improving functional independence; bracing may also be considered.15 Use of compression garments may be helpful for co-occurring lymphedema in the presence of pathologic fracture.
Coordination of care
A comprehensive team consisting of medical, surgical and radiation oncologists in addition to physiatrists, physical and occupational therapists should manage patients with bony metastases. Individualized rehabilitation programs can be designed based upon medical and surgical treatment.
Patient & family education
Patients and families should be educated about the individualized medical and surgical treatment plan in addition to the rehabilitation plan. Precautions and exercises should be explained in detail by the treating physiatrist and therapists to maximize safety. Open communication regarding goals and expectations of the treating team, patient and family should be emphasized during clinical visits and therapy sessions.
Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills
Any individual with a history of cancer or significant risk factors for cancer who presents with new pain, pathologic fracture or neurologic symptoms should be evaluated for an acute bony process, including metastatic bone disease. Unique rehabilitation prescriptions should provide sufficient detail to the treating therapists in order to simultaneously maximize function and safety.
4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE
Cutting edge concepts and practice
The use of different exercise regimens is currently being performed as discussed previously in regards to resistance exercises with respect to safety in patients with bone metastases.
5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE
Gaps in the evidence-based knowledge
Randomized controlled trials determining the optimal rehabilitation course for individuals with bone metastases have not yet been performed. The importance of bone markers regarding the predictive power of metastatic bone disease has yet to be fully investigated.16
- Li S, Peng Y, Weinhandl ED et al. Estimated number of prevalent cases of metastatic bone disease in the US adult population. Clin Epidemiol. 2012. 4:87-93.
- Mundy GR. Metastases to bone: Causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002. 2(8): 584-593.
- Hsiang-Hsuan MY, Ya-Yu T, Hoffe SE. Overview of the diagnosis and management of metastatic disease to bone. Cancer Control. 2012. 19(2):84-91.
- Coleman RE. Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity. Clin Cancer Res. 2006. 12(20 Suppl):6243s-6249s.
- Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. 2014. Annals of Oncology. 25(Supplement 3): iii124-iii137.
- Ashford RU and Randall RL. Bone Metastases: Epidemiology and Societal Effect. Metastatic Bone Disease. 2016. Springer Science+Business Media New York. DOI 10.1007/978-1-4614-5662-9_1
- Errani C, Mavrogenis AF, Cevolani L, et al. Treatment for long bone metastases based on a systematic literature review. Eur J Orthop Surg Traumatol. 2017. 27:205-211.
- Cheville AL, Murthy NS, Basford JR, et al. Imaging and Clinical Characteristics Predict Near-Term Disablement From Bone Metastases: Implications for Rehabilitation. Archives of Physical Medicine and Rehabilitation. 2016. 97: 53-60.
- Yamashiro H, Taka 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. 2014. 19:852-862.
- Pulido C, Vendrell I, Ferreira AR, et al. Bone metastasis risk factors in breast cancer. Ecancermedicalscience. 2017. 11:715.
- Petrylak DP. Risk Factors for the Development of Bone Metastases in Prostate Cancer. European urology supplements. 2007. 6(11). 677-682.
- Gralow JR, Biermann S, Farooki Z, et al. NCCN Task Force Report: Bone Health in Cancer Care. JNCCN. 2009. 7(Suppl 3): 1-32.
- Rosenthal DI. Radiologic diagnosis of bone metastases. Cancer. 1997. 80(8 suppl): 1595-1607.
- Rybak LD and DI Rosenthal. Radiological imaging for the diagnosis of bone metastases. QJ Nucl Med. 2001. 45: 53-64.
- Bunting RW and B Shea. Bone Metastases and Rehabilitation. 2001. Cancer. 92 (4 Suppl): 1020-1028.
- Coleman R, Costa L, Saad F, et al. Consensus on the utility of bone markers in the malignant bone disease setting. Critical Reviews in Oncology/Hematology. 2011. 80: 411-432.
- Tharmalingam S, Chow E, Harris K et al. Quality of life measurement in bone metastases: A literature review. J Pain Res. 2008. 1:49-58.
- Von Moos R, Body JJ, Egerdie B, et al. Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases. 2016. Supportive Care in Cancer. 24(3): 1327-1337.
- Peterson JR, Decilveo AP, O’Connor IT et al. What Are the Functional Results and Complications With Long Stem Hemiarthroplasty in Patients With Metastases to the Proximal Femur? Clinical Orthopaedics and Related Research. 2017. 475(3): 745-756.
- Jawad MU and SP Scully. Classifications in Brief: Mirels’ Classification: Metastatic Disease in Long Bones and Impending Pathologic Fracture. Clin Orthop Relat Res. 2010. 468: 2825-2827.
- Fourney DR, Frangou EM, Ryken TC et al. Spinal Instability Neoplastic Score: Analysis of Reliability and Validity From the Spine Oncology Study Group. Journal of Clinical Oncology. 2011. 29(22): 3072-3077.
- Mantyh P. Bone cancer pain: Causes, consequences, and therapeutic opportunities. Pain. 2013. 154: S54-S62.
- Wood TJ, Racano A, Yeung H, et al. Surgical Management of Bone Metastases: Quality of Evidence and Systematic Review. Ann Surg Oncol. 2014. 21: 4081-4089.
- Bunting R, Lamont-Havers W, Schweon D and A Kliman. Pathologic fracture risk in rehabilitation of patients with bony metastases. Clin Orthop Relat Res. 1985. 192: 222-227.
- Rief H, Welzel T, Omlor G, et al. Pain response of resistance training of the paravertebral musculature under radiotherapy in patients with spinal bone metastases – a randomized trial. BMC Cancer. 2014. 14: 485.
- Cormie P, Galvao DA, Spry N, et al. Functional benefits are sustained after a program of supervised resistance exercise in cancer patients with bone metastases: longitudinal results of a pilot study. Support Care Cancer. 2014. 22: 1537-1548.
Original Version of the Topic
Christian M. Custudio, MD, Jessica Au, MD, Jesuel Padro-Guzman M.D. Rehabilitation interventions for metastatic bone tumors. 09/20/2013.
Jesuel Padro-Guzman, MD
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