Guideline sources The following summarized guidelines for the evaluation and management of bone metastasis are prepared by our editorial team based on guidelines from the European Society of Medical Oncology (ESMO 2018; 2014) and the American Society for Radiation Oncology (ASTRO 2017). 1 2 3 4 4 5 6 Definition Bone metastasis is the development of secondary tumors within the bone of cancer patients characterized by pathological osteolytic, osteoblastic lesions or mixed. 4 Epidemiology Bone metastasis is caused by disseminated tumor cells from various common malignancies including breast, prostate, lung, and kidney cancers, or multiple myeloma. 4 Disease course The spread of tumor cells from the primary tumor to the bone results in pathologic osteolytic, osteoblastic (sclerotic), or mixed bone metastasis, which causes clinical presentation of severe pain, impaired mobility, pathologic fractures, spinal cord compression, bone marrow aplasia, and hypercalcemia. Disease progression is associated with increased morbidity and mortality. 5 https://web.pathway.md/diseases/rec8KskRG3U2FAb2n 1/5 6/29/23, 3:20 AM Bone metastasis Pathway Prognosis and risk of recurrence The 1-year survival of bone metastasis from breast, prostate, and lung cancers are 51%, 35%, and 10%, respectively. 6 Calculator Calculator Pathway Eastern Cooperative Oncology G Karnofsky performance status s Bone meta Managemen Guidelines 1. Screening and diagnosis Populations at risk: bone metastases are especially prevalent in advanced breast and prostate cancer. Pathophysiology: tumor cells home to the hematopoietic stem cell niches in bone, and these calls may remain dormant for long periods of time before progressing to overt metastases. Differential diagnosis: the differential diagnosis of metastatic bone disease includes osteoporosis, degenerative disease, and Paget's disease of bone. Complications of bone metastases: Metastatic bone disease is a major cause of morbidity in cancer. Complications of metastatic bone disease include pain, impaired mobility, pathological fracture, spinal cord compression, hypercalcemia and suppression of bone marrow function. 2. Diagnostic investigations Clinical assessment: assess symptoms and activity status in patients with bone metastases. Biochemical markers: avoid the routine use of biochemical markers of bone metabolism in patients with bone metastasis, although these may provide information on prognosis and response to bone-specific treatments. Bone scan: the isotope bone scan yields little information about the nature of skeletal pathology, even though it is a sensitive test to detect its presence. Computed tomography and magnetic resonance imaging: CT and MRI are the best imaging modalities to obtain structural information on skeletal damage from metastatic bone disease. Positron emission tomography: positron emission tomography scan provides functional information that may aid in diagnosis. https://web.pathway.md/diseases/rec8KskRG3U2FAb2n 2/5 6/29/23, 3:20 AM Bone metastasis Pathway DEXA scan: obtain DEXA scans in patients at risk for cancer treatment-induced accelerated bone loss. Skeletal radiography: skeletal radiography can identify response to treatment, but the information is delayed and the method insensitive. 3. Medical management General principles: provide multidisciplinary management to patients with metastatic bone disease, drawing from relevant expertise in radiation therapy, orthopedic surgery, radiology and palliative care medicine. B Indications for bone-targeted therapy: initiate bone-targeted therapy at diagnosis of metastatic bone disease, and continue such therapy indefinitely throughout the course of the disease. B Choice of antiresorptive agent: Use zoledronic acid as the most effective bisphosphonate for prevention of morbidity from metastatic bone disease. B Use denosumab as a more effective alternative to zoledronic acid for prevention of skeletal morbidity from solid tumours. B Management of bone pain: radium-223 is effective in reducing skeletal-related events, decreasing pain, and improving survival in castrate-resistant prostate cancer patients. A 4. Therapeutic procedures Indications for radiotherapy: offer radiotherapy as the treatment of choice for palliation of localized bone pain. B Dosing of radiotherapy: for patients with previously unirradiated painful bone metastases, high- quality data shows equivalent pain relief between a single 8 Gy fraction, 20 Gy in 5 fractions, 24 Gy in 6 fractions, and 30 Gy in 10 fractions. Inform patients that single fraction radiotherapy is associated with a higher incidence of retreatment to the same painful site than is fractionated treatment. A Radiotherapy for persistent or recurrent pain: consider re-treatment in patients with persistent or recurrent pain for > 1 month following external beam radiation therapy to symptomatic, peripheral bone metastases, while adhering to normal tissue dosing constraints described in the available literature. B Stereotactic body radiation therapy: consider advanced radiation therapy techniques like stereotactic body radiation therapy as the primary treatment for painful spine bone lesions or for spinal compression in the setting of a clinical trial or data registry. B Other procedural interventions: the use of surgery, radionuclides, bisphosphonates, or kyphoplasty/vertebroplasty does not obviate the need for external beam radiation therapy for patients with painful bone metastases. B https://web.pathway.md/diseases/rec8KskRG3U2FAb2n 3/5 6/29/23, 3:20 AM Bone metastasis Pathway 5. Preventative measures Prevention of bone metastases: offer bisphosphonates to postmenopausal women with breast cancer as they reduce the frequency of bone metastases and improve survival. A Prevention of treatment-induced bone loss: offer a bisphosphonate or denosumab to prevent bone loss associated with the use of ovarian suppressants or aromatase inhibitors in early breast cancer, or with the use of androgen deprivation therapy in prostate cancer. B Clinical findings Symptoms Past medical history Bone pain Breast cancer Confusion Cancer Constipation Kidney cancer Fecal incontinence Lung cancer Muscle weakness Lymphoma Nausea Multiple myeloma Urinary incontinence Prostate cancer Vomiting Thyroid cancer Weakness in the legs Lab findings serum calcium References 1. Coleman R, Body JJ, Aapro M et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2014 Sep;25 Suppl 3:iii124 37. Open 2. Lutz S, Balboni T, Jones J et al. Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline. Pract Radiat Oncol. 2017 Jan Feb;7 1 4 12. Open 3. Fallon M, Giusti R, Aielli F et al. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2018 Jul 24. Open 4. Mark Esposito, Theresa Guise, Yibin Kang. The Biology of Bone Metastasis. 2018 Jun 1;8 6):a031252.2018 Jun 1;8 6):a031252. Open 5. Filipa Macedo, Katia Ladeira, Filipa Pinho et al. Bone Metastases: An Overview. 2017 May 9;11 1 321.2017 May 9;11 1 321. Open 6. Elisabeth Svensson, Christian F Christiansen, Sinna P Ulrichsen et al. Survival after bone metastasis by primary cancer type: a Danish population-based cohort study. 2017 Sep 11;7 9):e016022.2017 Sep 11;7 9):e016022. Open https://web.pathway.md/diseases/rec8KskRG3U2FAb2n 4/5 6/29/23, 3:20 AM Bone metastasis Pathway 7. American Academy of Hospice and Palliative Medicine. Choosing Wisely AAHPM recommendations. Choosing Wisely. 2013. Open 8. American Society for Radiation Oncology. Choosing Wisely ASRO recommendations. Choosing Wisely. 2017. Open 9. Handkiewicz-Junak D, Poeppel TD, Bodei L et al. EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides. Eur J Nucl Med Mol Imaging. 2018 May;45 5 846 859. Open 10. Handkiewicz-Junak D, Poeppel TD, Bodei L et al. EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides. Eur J Nucl Med Mol Imaging. 2018 May;45 5 846 859. Open 11. Muhammad Umar Jawad, MD and Sean P. Scully, MD et al. In Brief: Classifications in Brief: Mirels Classification: Metastatic Disease in Long Bones and Impending Pathologic Fracture. Clin Orthop Relat Res. 2010 Oct; 468 10 2825 2827. Open https://web.pathway.md/diseases/rec8KskRG3U2FAb2n 5/5