INTRODUCTION — Bone metastases are a common manifestation of distant relapse from many types of solid cancers, especially those arising in the lung, breast, and prostate [1]. Bone metastases represent a prominent source of morbidity [2,3]. Skeletal-related events (SREs) that are due to bone metastases can include pain, pathologic fracture, hypercalcemia, and spinal cord compression. Across a wide variety of tumors involving bone, the frequency of SREs can be reduced through the use of osteoclast inhibitors, such as bisphosphonates or denosumab.
This topic will provide an overview of therapeutic options for management of adult patients with bone metastases from tumors other than multiple myeloma. An overview of the incidence, distribution, clinical presentation, and diagnosis of bone metastases is presented elsewhere, as are more detailed discussions of analgesic approaches for patients with pain related to bone metastases; the use of radiation therapy, bone-targeted radiopharmaceutical therapy, image-guided thermal ablation for bone metastases; management of pathologic and impending pathologic fractures; and the use of osteoclast inhibitors to prevent SREs in a wide variety of tumors associated with bone involvement. Specific issues related to bone metastases in patients with prostate cancer, multiple myeloma, and primary lymphoma of bone (PLB) are also discussed separately:
●(See "Epidemiology, clinical presentation, and diagnosis of bone metastasis in adults".)
●(See "Cancer pain management with opioids: Optimizing analgesia".)
●(See "Radiation therapy for the management of painful bone metastases".)
●(See "Bone metastases in advanced prostate cancer: Management", section on 'Bone-targeted radioisotopes'.)
●(See "Image-guided ablation of skeletal metastases".)
GENERAL APPROACH TO THE PATIENT — The goals of management for patients with bone metastases include maximizing pain or symptom control, preserving and restoring function, minimizing the risk for skeletal-related events (SREs), stabilizing the skeleton (if needed), and enhancing local tumor control. Therapeutic options include pain management/analgesia, which may be administered in parallel with osteoclast inhibitors (bone modifying agents), systemic anticancer therapy, radiation therapy (external beam radiation therapy [EBRT], stereotactic body radiation therapy [SBRT] in one to five fractions), bone-targeting radiopharmaceuticals, surgery (which is generally reserved for patients with a complete or impending pathologic fracture), and image-guided thermal ablation. (See "Clinical presentation and evaluation of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma".)
Factors influencing the choice of treatment — Factors influencing the choice of treatment for a patient with bone metastases include symptoms, impact of bone metastases on quality of life, performance status, estimated life expectancy, goals of treatment, and preferences for care. Other factors include the clinical disease status (eg, whether an individual has an uncontrolled primary cancer with diffuse, visceral metastases versus a controlled primary with just a few sites of metastasis, termed oligometastatic disease, as well as the length of the disease-free interval if the site represents progression of disease at a follow-up time point) and whether or not there is an impending or existing fracture in the affected bone.
For patients with vertebral bone metastases, the specific approach also depends on whether or not the spinal cord or cauda equina are at risk due to epidural tumor extension. Decision-making about surgical versus nonsurgical treatment in these patients can be difficult. A decision framework that is based on neurologic (extent of cord compression, presence or absence of myelopathy), oncologic (radiosensitivity of the malignancy, prior irradiation), mechanical (is there spinal instability), and systemic factors (able to tolerate surgery) has been developed to assist in the decision-making process [4]. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Baseline assessment'.)
Optimal treatment of bone metastasis may be complex and require multimodality treatment strategies to achieve optimal outcomes. Treatment recommendations must be individualized to each patient's specific symptoms, clinical presentation, histologic tumor type, performance status, and his or her goals and preferences. As examples:
●Observation may be recommended for asymptomatic bone metastasis with no significant risk of pathologic fracture or spinal instability, especially if life expectancy is limited.
●Evaluating the extent of disease, both local bony and systemic, as well as the natural history of the underlying primary malignancy, is important to establish the goals of treatment. For example, patients with a few focal, isolated bone metastases and a primary radioresistant histology, such as renal cell carcinoma, may be candidates for aggressive local surgical or radioablative management. (See "Role of surgery in patients with metastatic renal cell carcinoma", section on 'Isolated bone metastases' and "Image-guided ablation of skeletal metastases".)
●The efficacy of systemic anticancer therapy based on primary tumor type is also a factor. As an example, systemic therapy plays a major role in treatment for patients with castration-resistant prostate cancer with symptomatic bone metastases. (See 'Systemic anticancer therapy' below.)
●Moribund or severely medically ill patients who are not expected to survive the procedure (let alone the hospitalization) should not be offered operative intervention, even if they have a complete or impending pathologic fracture. In such cases, nonsurgical stabilization (eg, bracing a limb or wearing a neck collar for stabilization) with adequate analgesia and/or other nonsurgical palliative therapy may be a more appropriate option. (See "Management of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Palliation to exceed expected survival'.)
Predicting prognosis — Models to predict prognosis in patients with bone metastases that are based on the number of skeletal metastases, presence and extent of organ metastases, primary site, hemoglobin level, and performance status (table 1) have been developed, several of which are specific to spine metastases [5-9]. However, all are limited in their ability to accurately predict overall survival, and it is not clear that any one is more reliable than the others.
These issues and additional tools for estimating survival in patients with advanced cancer are discussed separately. (See "Management of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Palliation to exceed expected survival' and "Survival estimates in advanced terminal cancer".)
Supportive care — For patients with bone metastases, supportive care should include adequate analgesia, if pain is present, and the use of osteoclast inhibitors to reduce the risk of SREs (including bone pain, pathologic fracture, hypercalcemia, and spinal cord compression) and to enhance analgesia.
Analgesia — The majority of patients who develop bone metastases will suffer from significant bone pain at some point. Initially, nonopioid analgesic drugs, such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), may be used alone for mild to moderate pain. When pain is not adequately relieved, these nonopioid analgesic drugs may be used in combination with an opioid. Although there are several products available that combine an opioid and acetaminophen, hepatic toxicity from acetaminophen is a major concern, and the therapeutic dose of the combination is limited by the amount of acetaminophen. (See "Cancer pain management: Use of acetaminophen and nonsteroidal anti-inflammatory drugs", section on 'Hepatic toxicity'.)
For moderate or severe cancer pain, opioids are the most common medical therapy because they are effective for all types of cancer pain. The majority of patients with pain from metastatic bone disease obtain adequate pain relief with opioid therapy [10,11]. Optimal pain control usually requires titration, the addition of long-acting opioids, and effective management of breakthrough pain. (See "Cancer pain management with opioids: Optimizing analgesia" and "Cancer pain management with opioids: Optimizing analgesia", section on 'Pure mu agonists rarely used for cancer pain' and "Cancer pain management with opioids: Optimizing analgesia", section on 'Dose titration' and "Cancer pain management with opioids: Optimizing analgesia", section on 'Management of breakthrough pain'.)
Patients with multifocal bone pain usually are managed with an NSAID, with or without opioids, unless they have a specific contraindication to use of these agents in conjunction with an opioid. (See "Cancer pain management with opioids: Optimizing analgesia" and "Cancer pain management: Role of adjuvant analgesics (coanalgesics)", section on 'Patients with bone pain'.)
Glucocorticoids may be helpful for patients with somatic pain from bone metastases whose pain is incompletely resolved with opioids with or without NSAIDs or for whom side effects are limiting. Consultation with a palliative care specialist should be considered for patients whose pain is refractory to initial attempts at analgesic therapy or who develop significant side effects from the agents initially chosen. Other adjuncts include antidepressants and antiepileptics such as gabapentin, which may be effective for tingling and burning pain. (See "Cancer pain management: Role of adjuvant analgesics (coanalgesics)" and "Benefits, services, and models of subspecialty palliative care".)
Consultation with an anesthesia pain specialist can be considered for integration of interventional procedures (eg, nerve block, spinal cord stimulator, epidural port-a-cath, or implanted pain pump that delivers local analgesia or a combination of low-dose opioid and local analgesia to prevent the side effects and quality of life decrement with high-dose, systemically administered opioids). Chest wall and rib metastasis, for example, may respond significantly to a local pain block. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care' and "Cancer pain management: Interventional therapies".)
Osteoclast inhibitors — Osteoclast inhibitors (including bisphosphonates and denosumab) are indicated for the management of metastatic bone disease for most patients with solid tumors. However:
●The vast majority of the data regarding the benefits of osteoclast inhibitors for prostate cancer were generated in the castration-resistant state; hence, for men with bone metastases from prostate cancer, the use of osteoclast inhibitors is generally restricted to those with castration-resistant disease. (See "Bone metastases in advanced prostate cancer: Management", section on 'Castration-resistant disease'.)
●For patients in whom SREs are unlikely (eg, those with minimal bone tumor burden) and those with a limited expected survival (eg, in the setting of widespread and progressive, visceral metastases), treatment with osteoclast inhibitors should be considered on a case-by-case basis. (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors", section on 'Indications for osteoclast inhibitor therapy'.)
Osteoclast inhibitors slow or reverse the progression of skeletal metastases and reduce the likelihood of SREs. In addition, they also have some analgesic benefit, although it is modest. In several trials, denosumab has proven modestly superior to bisphosphonates for prevention of SREs and in analgesic efficacy. However, the analgesic efficacy of all of these agents is limited, and they are not recommended as first-line agents to treat painful bone metastases. (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors", section on 'Efficacy and dosing considerations for individual agents'.)
The modest benefits of denosumab over zoledronic acid for patients with skeletal metastases come at a higher direct cost. Moreover, there are sufficient data in breast cancer and castration-resistant prostate cancer to support a 12-week, rather than four-week, dosing interval for zoledronic acid, which improves indirect costs. As a result, for many patients, zoledronic acid is the preferred agent. This subject is discussed in detail elsewhere. (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors", section on 'Overview of the approach to osteoclast inhibition'.)
Although generally well tolerated, the bisphosphonates and denosumab are associated with side effects, some of which (jaw osteonecrosis, hypocalcemia [especially in vitamin D-deficient patients]) are shared. (See "Risks of therapy with bone antiresorptive agents in patients with advanced malignancy", section on 'Risks shared by both classes of drugs' and "Medication-related osteonecrosis of the jaw in patients with cancer".)
Risks specific to bisphosphonates in patients with malignancy include impaired renal function, a temporary flu-like syndrome with fever and body aches, and a significantly increased risk of atrial fibrillation/flutter and stroke. (See "Risks of therapy with bone antiresorptive agents in patients with advanced malignancy", section on 'Risks specific to bisphosphonates'.)
Risks specific to denosumab include an increased risk of infection. (See "Risks of therapy with bone antiresorptive agents in patients with advanced malignancy", section on 'Risks specific to denosumab'.)
Exercise — If consistent with the goals of care, individuals with bone metastases should be supported and encouraged to engage in regular physical activity. Perceived risks of skeletal complications must be weighed against the potential health benefits, in consultation with the patient, the health care team, and the exercise professional.
There is increasing evidence that engaging in regular physical activity or exercise improves physical function, and reduces treatment-related side effects and cancer-related fatigue and the psychosocial burden of living with cancer. However, until recently there was little information to guide such recommendations for those living with bone metastases. (See "Cancer-related fatigue: Treatment", section on 'Exercise' and "Side effects of androgen deprivation therapy", section on 'Role of structured exercise'.)
An international expert consensus group reviewed the current evidence and outlined best practice recommendations for exercise in patients with bone metastases for health care providers and exercise professionals [12]. The key recommendations were:
●Integration of regular exercise in those with bone metastases has the potential to maintain or improve physical function and health-related quality of life, decrease side effects relating to cancer treatment in people with bone metastases, and improve resilience. The perceived risk of skeletal complications should be weighed against these potential health benefits.
●Before exercise testing or training, perform a risk assessment to inform the likelihood of a skeletal complication from exercise. For those considered to be at higher risk for a skeletal complication, a volume-based imaging study such as CT or MRI was recommended to provide more information on the burden of the lesion(s).
●Consultation with the medical team is strongly encouraged before an exercise professional provides a structured exercise program to a person with bone metastases, to obtain key medical information, and establish bidirectional communication for initial assessment and exercise training during care.
●Exercise professionals best suited to prescribe exercise to patients with bone metastases are physical therapists and clinical exercise physiologists (or equivalent), who have additional cancer exercise training and appropriate experience in working with people with a cancer diagnosis.
●Professional judgement should be used to consider if exercise testing at baseline and at follow-up is necessary by weighing the risks and benefits of including the test, or if the testing protocols may need to be modified.
●Exercise prescription should follow the standard exercise recommendations as outlined by the International Exercise Guidelines for Cancer Survivors from the American College of Sports Medicine [13], with greater emphasis on postural alignment, controlled movement, and proper technique, as well as consideration given to the location and presentation of the bone lesions. Formal monitoring and adjustment of exercise prescription should be ongoing.
Further trials are needed to study the effects of exercise on this specific population and to evaluate the efficacy of those taking bone modifying agents.
Systemic anticancer therapy — Chemotherapy, targeted therapies, and hormone therapy may contribute to pain relief by reducing tumor bulk and/or by modulating pain signaling pathways [14,15]. However, primary tumor type, disease extent, and treatment-related toxicity are important considerations:
●Systemic therapy plays a major role in treatment in the setting of castration-resistant prostate cancer with symptomatic bone metastases. (See "Overview of the treatment of castration-resistant prostate cancer (CRPC)" and "Overview of systemic treatment for advanced, recurrent and metastatic castration-sensitive prostate cancer and local treatment for patients with metastatic disease" and "Bone metastases in advanced prostate cancer: Management".)
●For patients with breast cancer, limited disease bulk, and more favorable features (such as a hormone receptor-positive metastasis 10 years after modified radical mastectomy for invasive ductal breast cancer), initiation of aromatase inhibitors or antiestrogens may be sufficient for pain relief and disease control. However, many patients present with unfavorable features (eg, an extensive disease burden with visceral as well as bone metastases). In this setting, pain relief is usually not swiftly achieved, and patients may not have a sufficient performance status to tolerate chemotherapy. (See "Treatment approach to metastatic hormone receptor-positive, HER2-negative breast cancer: Endocrine therapy and targeted agents".)
●Chemotherapy may also cause painful side effects or be complicated by side effects that limit the effective dose that can be administered, such as neuropathy (eg, platinum, taxanes, vinca alkaloids). Newer biologic or molecularly targeted agents have fewer side effects and may be more tolerable. However, like chemotherapy, they are not associated with immediate pain relief.
For all of these reasons, palliative local therapy (eg, radiation therapy) is often considered prior to or concurrent with systemic anticancer therapies. Multidisciplinary consultation with the appropriate medical oncologist can help personalize systemic options for treatment to the individual patient's disease status. (See "Overview of systemic treatment for advanced, recurrent and metastatic castration-sensitive prostate cancer and local treatment for patients with metastatic disease", section on 'Androgen deprivation therapy' and "Overview of the treatment of castration-resistant prostate cancer (CRPC)" and "Treatment approach to metastatic hormone receptor-positive, HER2-negative breast cancer: Endocrine therapy and targeted agents", section on 'General principles'.)
If systemic therapy is chosen as primary therapy, it is essential to have consistent, reproducible, and validated methods of assessing response of bone metastases to therapy [16,17]. Criteria for assessment of disease response in bone from the World Health Organization (WHO) and the Union for International Cancer Control (UICC) are presented in the table (table 2).
Local treatment options — There are several options for local therapy, and the choice of approach must be individualized. Suggested general approaches to local treatment of vertebral and nonvertebral bone metastases are outlined in the algorithms (algorithm 1 and algorithm 2), and the data to support specific approaches are discussed in the sections below.
RADIATION THERAPY — External beam radiation therapy (EBRT) is a standard approach for symptomatic skeletal metastases, achieving pain reduction in 50 to 80 percent, which is complete in up to one-third of patients. For uncomplicated bone metastases, a single fraction of 8 Gy to the involved area provides equivalent pain palliation and is more cost-effective and convenient than fractionated regimens, although retreatment is needed more often.
External beam radiation therapy — A number of clinical trials have demonstrated that short fractionation schedules are as effective as more protracted schedules, although more frequently associated with a need for retreatment [18]. A single fraction of 8 Gy to the involved area has been shown to provide equivalent pain palliation and may be more cost-effective and convenient, compared with fractionated regimens, for uncomplicated bone metastases, and guidelines from the American Society for Radiation Oncology (ASTRO) and the European Society of Medical Oncology (ESMO) support this regimen [19,20]. Approximately 20 percent of patients may require retreatment after a single fraction of 8 Gy, compared with 8 percent for those who received a fractionated regimen. However, recurrence rates are not substantially different for the first two to three months post-treatment [18]. With a short life expectancy, as with many palliative care patients, this may be long enough so that recurrence is not a major concern. (See "Radiation therapy for the management of painful bone metastases", section on 'External beam radiation therapy'.)
Stereotactic body radiation therapy — Stereotactic body radiation therapy (SBRT) utilizes precisely targeted radiation to a tumor while minimizing radiation to adjacent normal tissue, allowing treatment of small or moderate-sized tumors in either a single or a limited number of dose fractions. SBRT may have a role in treating selected patients with small-volume, painful bone oligometastases. At least in the spine, the use of SBRT might be associated with a higher risk of vertebral compression fractures. In our view and that of others [21], SBRT should be reserved mostly for patients who have a reasonable (>6 months) life expectancy, persistent or recurrent bone pain after a standard course of EBRT, and require reirradiation. This view is in keeping with evidence-based guidelines on palliative radiation therapy (RT) for bone metastases from ASTRO [21]. (See "Radiation therapy for the management of painful bone metastases", section on 'Stereotactic radiation therapy'.)
There are some settings in which SBRT may be preferred over EBRT:
●One setting in which SBRT may be preferred over EBRT is in the definitive treatment of patients with symptomatic bone metastases from relatively radioresistant neoplasms (eg, renal cell cancer, melanoma, sarcoma), especially in the setting of vertebral metastases with epidural extension but no high-grade epidural spinal cord compression. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Stereotactic body radiotherapy'.)
●Another situation in which SBRT may be preferred is in patients with oligometastatic disease who have a relatively long life expectancy [22]:
In this setting, options range from single doses as well as fractionated regimens, with early data suggesting the potential for improved outcomes with single-fraction treatment. This was shown in a randomized study that directly compared single-fraction SBRT (24 Gy) versus a three-fraction SBRT regimen (27 Gy at 9 Gy per fraction given every other day) in patients with <5 metastatic lesions, nonmobile, <6 cm in size in bone, lymph nodes, or both provided that the lesions were not abutting critical organs/structures and could be treated to the prescribed dose [23]. Biologically, the 24 Gy single-dose regimen has a calculated biologically effective dose (BED) of 81.60 Gy assuming α/β = 10, which is higher than that of the 27 Gy/three-fraction regimen, where BED is calculated to be 51.3 Gy.
The single-fraction regimen was associated with a significantly lower risk of three-year local recurrence (5.8 versus 22 percent, p = 0.0048), as well as a lower risk of distant metastases (5.3 versus 10.7 percent, p = 0.010). The rate of grade 3 toxicity was 7.8 percent in the single-fraction versus 3.9 percent in the three-fraction regimen, and this difference was not significant, p = 0.49.
These data suggest that more effective ablation of oligometastatic disease may be associated with a reduction in distant metastatic progression. The rate of development of distant metastases in this study was lower than that seen in other studies of SBRT for oligometastatic disease [22], suggesting that the patient population was highly selected. Because single-fraction SBRT has been associated with a higher rate of compression fractures [24] and the reported results by Zelefsky et al are from clinicians with extensive experience with single-fraction treatment, it remains to be seen whether clinicians move to more broadly adopt the single-fraction regimen or alternatively use multiple-fraction regimens with a higher BED than the 27 Gy/three-fraction regimen used in this study.
Future efforts to determine which patients with oligometastatic disease benefit and when in the course of their cancer treatment these ablative treatments offer the most benefit are important areas for further study.
●SBRT may provide a greater degree of pain control and a more prolonged duration of local control compared with multiple-fraction EBRT in symptomatic patients who have nonspine metastases and an estimated prolonged life expectancy (up to two years) [25].
However, there are conflicting data on whether SBRT is better than EBRT for symptom control in patients with symptomatic spine metastases. These data are presented in detail elsewhere. (See "Radiation therapy for the management of painful bone metastases", section on 'Stereotactic radiation therapy'.)
Diffuse bone pain — Some patients with multiple bone metastases have diffuse pain that is not easily managed by focal radiation. There are two options in such circumstances: bone-targeted radiopharmaceutical therapy and hemibody irradiation. Although hemibody irradiation can provide rapid pain relief when multiple sites of symptomatic bone metastases are present, its use has largely been replaced, at least for advanced prostate cancer, by the administration of bone-targeted radiopharmaceuticals, which offer a similar degree of pain relief and may be associated with less toxicity. Hemibody irradiation is discussed in more detail elsewhere. (See "Radiation therapy for the management of painful bone metastases", section on 'Hemibody irradiation'.)
For men with castration-resistant prostate cancer, multifocal painful osteoblastic bone metastases, and no visceral metastases, radium-223 is a reasonable initial approach to management. For other histologic cancer types, bone-targeted radiopharmaceuticals are generally reserved for individuals with persistent or recurrent multifocal bone pain after EBRT and/or other forms of therapy. In this setting, samarium-153 is a reasonable option for patients with diffuse osteoblastic bone pain from other histologies, such as breast cancer, but we would not use radium-223.
Bone-targeted radiopharmaceutical therapy — Bone-targeted radiopharmaceuticals are radioactive bone-seeking molecules that are approved for the palliation of painful osteoblastic bone metastasis. Three are commercially available in the United States (see "Bone metastases in advanced prostate cancer: Management", section on 'Bone-targeted radioisotopes'):
●Samarium-153 lexidronam (153Sm) and strontium-89 (89Sr) emit beta particles and are effective for palliation of pain, with response rates between 40 and 95 percent [26]. However, the onset of pain relief is slower than with EBRT, taking up to two to four weeks, patients can have prolonged hematologic toxicity (more prominent with 89Sr than 153Sm), and they do not improve survival.
In the United States, 153Sm is approved for the relief of pain in patients with confirmed osteoblastic bone lesions that enhance on radionuclide bone scan, while 89Sr is approved for the relief of bone pain in patients with painful skeletal metastases. Both agents are generally reserved for individuals with persistent or recurrent multifocal bone pain after EBRT and/or other forms of therapy.
●Radium-223 is a new class of intravenously injected bone-targeted radioisotopes; the advantage of these alpha emitters is that they deposit high-energy radiation over a much shorter distance than the beta particles emitted by 153Sm or 89Sr. Radium-223 has been approved by the US Food and Drug Administration (FDA) for treatment of men with castration-resistant prostate cancer, multifocal symptomatic bone metastases, and no known visceral metastatic disease. Approval was based on a phase-III study, which demonstrated improved overall survival and time to first symptomatic skeletal-related event (SRE) in such patients. (See "Bone metastases in advanced prostate cancer: Management", section on 'Radium-223' and "Radiation therapy for the management of painful bone metastases", section on 'Bone-targeted radioisotopes'.)
Indications for bone-targeted radiopharmaceutical therapy include positive bone scan, refractory bone pain despite analgesic, life expectancy >3 months, and no chemotherapy or bisphosphonate six weeks prior to treatment. Contraindications of bone-targeted radiopharmaceutical therapy include acute or chronic renal failure, acute spinal cord compression, pregnancy, breastfeeding, and myelosuppression.
The vast majority of efficacy data for all bone-targeted radiopharmaceuticals are in patients with metastatic prostate (especially for radium-223) and breast cancer. Data on other tumor types are extremely limited, although clinical trials are underway examining the efficacy of radium-223 in a variety of solid tumor types. Until further data become available, we restrict use of radium-223 to prostate cancer. For other histologic types for which bone-targeted radiopharmaceuticals are being considered, we would use 153Sm.
INDICATIONS FOR SURGICAL CONSULTATION — Surgical management of bone metastases is typically reserved for lesions with a complete or impending pathologic fracture, if surgical intervention is consistent with the goals of care. Surgery may also be needed for spine metastases that are causing mechanical instability or epidural spinal cord compression (ESCC).
The majority of patients without an impending or complete fracture or evidence of ESCC do not require surgery for bone metastasis. However, for highly selected patients with advanced cancer who present with or develop a bone lesion as the only focus of cancer beyond the primary site, en bloc resection of the metastasis may optimize local tumor control, provide durable pain relief, and possibly prolong patient survival. However, curative resection is rare for bone metastasis, except for selected patients with isolated spine or sternal involvement. (See "Role of surgery in patients with metastatic renal cell carcinoma", section on 'Isolated bone metastases'.)
For patients with long bone or spinal metastases, postoperative radiation therapy is generally given after surgical stabilization to promote remineralization and bone healing, alleviate pain, improve functional status, and reduce the risk for subsequent fracture or loss of fixation by treating residual metastatic disease. (See "Management of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Postoperative radiation therapy'.)
Nonvertebral bones
Impending or complete fractures — For patients with an impending or complete pathologic fracture of a long bone, the goals of treatment are to palliate pain, minimize morbidity, and maximize function and skeletal integrity for the duration of the patient's remaining lifespan. If a pathologic fracture of a long bone is present, it is often best treated with internal fixation and instrumentation. Prophylactic fixation of an impending pathologic fracture may be considered for patients with a high risk for pathologic fracture as assessed by Mirels criteria, which are based on the lesion site, lesion type, lesion size, and the level of pain (table 3). Prophylactic fixation is recommended for score of 9 or greater, with consideration for prophylactic fixation for score of 8. Lesions with score of 7 or less may be managed with radiation therapy and pain management [27,28]. (See "Clinical presentation and evaluation of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Mirels scoring system'.)
Operations are rarely required for complete or impending pathologic fractures of the pelvis other than for those involving the acetabulum. (See "Management of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Pelvis lesions'.)
In a systematic review of 45 studies addressing the role of surgical management of bone metastases involving the humerus, femur, and pelvis/acetabulum (47 percent of cases with a pathologic fracture), surgery was associated with significant pain relief in 91 to 93 percent of cases, and function was maintained or improved in 89 to 94 percent [26]. The rates of perioperative complications and mortality were 17 and 4 percent, respectively.
No impending or complete fracture — The majority of patients without an impending or complete fracture do not require surgery for bone metastasis. However, for highly selected patients with advanced cancer who present with or develop a bone lesion as the only focus of cancer beyond the primary site, en bloc resection of the metastasis may optimize local tumor control, provide durable pain relief, and possibly prolong patient survival [29-40]. In general, curative resection is rare for bone metastasis, except for selected patients with isolated spine or sternal involvement. (See "Role of surgery in patients with metastatic renal cell carcinoma", section on 'Isolated bone metastases'.)
Vertebral bones
Cord compression and mechanical instability — Surgical consultation should be sought for patients with spine metastases with associated ESCC or vertebral column instability.
Operative treatment may be indicated for patients with symptomatic vertebral body fractures that are causing instability. The spine instability neoplastic score (SINS) has been developed to determine mechanical stability of the spine due to vertebral metastasis. Consultation with a surgeon skilled in spine surgery (orthopedic spine surgeon or a neurosurgeon) is recommended for patients with SINS scores greater than 7 (table 4) [41,42]. (See "Clinical presentation and evaluation of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Assessing spinal stability'.)
Patients with progressive neurologic deterioration due to ESCC require immediate consideration of surgical decompression followed by postoperative radiation therapy as the chance of regaining and maintaining ambulation is improved with this combination therapy [43]. In selected patients who have limited vertebral metastasis, limited surgical decompression may be performed, followed by stereotactic body radiation therapy (SBRT); this approach is best suited with multidisciplinary evaluation. If a patient presents with an unknown primary and neurologic compromise, an additional benefit of surgery will be the acquisition of sufficient tissue to clarify the histologic diagnosis. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Surgical decompression and spine stabilization'.)
Given the complexity of the treatment decisions, multidisciplinary evaluation is usually necessary to determine the optimal approach to patients with spinal metastases. A decision framework that is based on neurologic, oncologic, mechanical, and systemic factors has been developed to assist in the decision-making process [4]. (See 'Factors influencing the choice of treatment' above.)
VERTEBROPLASTY AND KYPHOPLASTY — Another option for patients with painful vertebral bone metastases with a compression fracture is percutaneous vertebral augmentation, with (vertebroplasty) or without (kyphoplasty) polymethyl methacrylate. Percutaneous vertebral augmentation has been used to improve the mechanical stability of the vertebrae as well as pain from a vertebral compression fracture [44]. However, only one randomized study has demonstrated improved quality of life and functional outcomes [45]; further research is thus needed. When it is performed, vertebroplasty/kyphoplasty is generally reserved for patients with symptomatic osteolytic spinal metastases, with intact bone cortex and without epidural disease, spinal cord compression, or retropulsion of bone fragments into the spinal cord. For asymptomatic patients with radiographic evidence of significant compromise of mechanical stability due to osteolytic bone metastasis or fracture, vertebral augmentation may be considered by the multidisciplinary team to prevent future symptoms due to further compression of vertebrae.
Occasionally, cementoplasty with polymethyl methacrylate may be considered for lytic metastasis involving the sacral iliac bone as well as the acetabulum to improve mechanical stability.
This subject is discussed in detail separately. (See "Management of complete and impending pathologic fractures in patients with metastatic bone disease, multiple myeloma, and lymphoma", section on 'Kyphoplasty versus vertebroplasty'.)
LOCAL ABLATION — For patients who have persistent or recurrent pain attributed to one or a few skeletal sites with small volume disease after palliative radiation therapy and who are not candidates for surgery or reirradiation with stereotactic techniques, local thermal ablation is an important therapeutic option. Radiofrequency ablation, cryoablation, and focused ultrasound are all effective ablative treatments for palliation of symptomatic skeletal metastases. When thermal ablation is applied to vertebral metastasis, the treatment volume should be at least 10 mm away from a neural structure to prevent neurologic complications. There are no randomized trials comparing these procedures, and the choice of ablation technique should take into account availability, patient preference, and local expertise, as well as involvement of the multidisciplinary team.
Patients should have at least moderate pain levels, pain referable to a limited number of metastases that are visible on imaging, and target lesions that are remote (or separable) from normal critical structures. Absolute contraindications to thermal ablation include uncorrectable bleeding diatheses, inability of the patient to tolerate the level of anesthesia required to perform the procedure, and inaccessibility of the target lesion from a percutaneous approach. Relative contraindications include widespread skeletal metastases, the presence of active infection, or tumor location adjacent to a critical normal structure that cannot be displaced or monitored adequately to allow safe ablation. This subject is discussed in detail elsewhere. (See "Image-guided ablation of skeletal metastases".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Neoplastic epidural spinal cord compression" and "Society guideline links: Cancer pain" and "Society guideline links: Management of bone metastases in solid tumors".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Bone metastases (The Basics)")
SUMMARY AND RECOMMENDATIONS
●General approach, goals of management, and supportive care
•The goals of management for patients with symptomatic bone metastases include pain control, preserving and restoring function, minimizing the risk of skeletal-related events (SREs), stabilizing the bone (if needed), and enhancing local tumor control. (See 'General approach to the patient' above.)
•Supportive care for symptomatic patients should include adequate analgesia (typically opioids, with or without an analgesic adjuvant), and osteoclast inhibitors to enhance analgesia and reduce the risk of SREs (ie, bone pain, pathologic fracture, hypercalcemia, and spinal cord compression). Interventional procedures such as nerve blocks may help when opioid analgesics are maximized. (See 'Supportive care' above.)
•If consistent with the goals of care, individuals with bone metastases should be supported and encouraged to engage in regular physical activity. Perceived risks of skeletal complications must be weighed against the potential health benefits, in consultation with the patient, the health care team, and the exercise professional. (See 'Exercise' above.)
●Choice of local treatment
•Factors influencing the choice of local treatment include symptoms, impact of bone metastases on quality of life, performance status, estimated life expectancy, goals preferences for care, clinical disease extent, whether or not there is an impending or existing fracture in the affected bone, and, for patients with vertebral bone metastases, whether epidural tumor extension is present. (See 'Factors influencing the choice of treatment' above.)
•The choice of a specific approach must be individualized. Management algorithms for local treatment of vertebral and nonvertebral bone metastases are provided (algorithm 1 and algorithm 2).
In general:
-Asymptomatic patients with widespread metastasis, no risk of impending fracture, and a limited life expectancy may not require any intervention.
-External beam radiation therapy (EBRT) is a standard approach for symptomatic skeletal metastases. For uncomplicated bone metastases, a single fraction of 8 Gy to the involved area is effective and more convenient than fractionated regimens, although retreatment is needed more often. (See 'External beam radiation therapy' above.)
-Stereotactic body radiation therapy (SBRT) is generally reserved for recurrent vertebral metastases that require reirradiation for symptomatic control, or SBRT may be preferred over EBRT for definitive treatment of symptomatic bone metastases from relatively radioresistant neoplasms (eg, renal cell cancer, melanoma, sarcoma), especially in patients with vertebral metastases and epidural extension but no high-grade epidural spinal cord compression (ESCC). Another setting in which SBRT may be preferred is for patients with oligometastatic disease. (See 'Stereotactic body radiation therapy' above and "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Stereotactic body radiotherapy'.)
-Radium-223 is a reasonable option for men with castration-resistant prostate cancer, multifocal symptomatic osteoblastic bone metastases, and no visceral metastases. For other histologies, bone-targeted radiopharmaceuticals are reserved for persistent or recurrent multifocal bone pain from osteoblastic metastases after EBRT and/or other forms of therapy. In this setting, samarium-153 is a reasonable option, but we would not use radium-223. (See 'Bone-targeted radiopharmaceutical therapy' above.)
-Surgical management of bone metastases is typically reserved for lesions with a complete or impending pathologic fracture if surgical intervention is consistent with the goals of care. Surgery may also be needed for spine metastases that are causing mechanical instability or ESCC. (See 'Indications for surgical consultation' above.)
For highly selected patients with advanced cancer who present with or develop a bone lesion as the only focus of cancer beyond the primary site, en bloc resection of the metastasis may optimize local tumor control, provide durable pain relief, and possibly, prolong patient survival. (See "Role of surgery in patients with metastatic renal cell carcinoma", section on 'Isolated bone metastases'.)
-Vertebroplasty and kyphoplasty are generally reserved for patients with symptomatic osteolytic spinal metastases causing vertebral compression fracture, without epidural disease or retropulsion of bone fragments into the spinal cord. (See 'Vertebroplasty and kyphoplasty' above.)
-For patients with persistent or recurrent pain from one or a few skeletal sites after palliative RT and who are not surgical candidates, local thermal ablation (radiofrequency ablation, cryoablation, and focused ultrasound) is an important therapeutic option. (See 'Local ablation' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thomas F DeLaney, MD, who contributed to earlier versions of this topic review.
