Bone metastases in advanced prostate cancer. Management

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6/20/22, 12:19 AM 17128COMPLICATIONS FROM BONE METASTASESThe term "skeletal related events" (SREs) refers to a constellation of complications (pain,fracture, epidural spinal cord compression, need for radiation therapy or surgery for a bonemetastasis) that arise in patients who have bone metastases. Symptomatic SREs are clinicallydetectable events that do not depend on routine acquisition of imaging. Pain is the mostcommon symptom in metastatic bone disease. (See "Epidemiology, clinical presentation, anddiagnosis of bone metastasis in adults", section on 'Clinical presentation'.)MANAGING PATIENTS WITH SYMPTOMATIC BONE METASTASESThere are several approaches to managing pain and other skeletal-related events (SREs) in menwith metastatic prostate cancer. In general, systemic therapy is an important component ofpatient management for controlling symptoms and slowing progression of bone metastases.External beam radiation therapy (EBRT) is the treatment of choice for men with metastaticprostate cancer and bone pain that is not responsive to systemic therapy and limited to one ora limited number of sites.The utility of other therapies, including bone-targeted radioisotopes, bisphosphonates, focusedultrasound, and surgery, is limited to selected populations and is reviewed in the sectionsbelow.Analgesics — A range of pharmacologic agents are available to treat cancer-related bone painthat is not adequately controlled by measures specifically directed against the metastaticdisease. In addition to opioids, which are a mainstay of treatment for painful bone metastases,these include adjuvants, such as nonsteroidal anti-inflammatory drugs, and osteoclastinhibitors, such as bisphosphonates. (See 'Bisphosphonates' below.)A wide variety of issues relating to optimal pain management in cancer patients are discussedseparately. (See "Cancer pain management: General principles and risk management forpatients receiving opioids" and "Cancer pain management with opioids: Optimizing analgesia"and "Cancer pain management: Use of acetaminophen and nonsteroidal anti-inflammatorydrugs" and "Cancer pain management: Role of adjuvant analgesics (coanalgesics)" and"Psychological, rehabilitative, and integrative therapies for cancer pain" and "Cancer painmanagement: Interventional therapies".)Systemic anticancer therapy — Systemic anticancer treatment is an important component ofcare for men with metastatic prostate cancer causing bone metastases. Systemic therapies forhttps://www.uptodate.com/contents/17128/print 2/27
6/20/22, 12:19 AM 17128metastatic castration-resistant prostate cancer (CRPC) such as abiraterone/prednisone,enzalutamide, Radium-233 (Ra-223), docetaxel, cabazitaxel, and mitoxantrone have all beenshown to reduce SREs and improve bone pain and health-related quality of life in men withmetastatic CRPC. Specific examples of some of these treatments are outlined in the table (table 1). However, the optimal sequencing or combination of these therapies with bonetargetedagents (including Ra-223) is unclear [1,2].The use of androgen deprivation therapy as initial therapy for castration-sensitive metastaticdisease, and various other modalities for castration-resistant metastatic prostate cancer arediscussed separately. (See "Overview of systemic treatment for advanced, recurrent andmetastatic castration-sensitive prostate cancer and local treatment for patients with metastaticdisease" and "Overview of the treatment of castration-resistant prostate cancer (CRPC)".)External beam radiation therapy — EBRT is the treatment of choice for men with CRPC andbone pain that is not responsive to systemic therapy and limited to one or a limited number ofsites [1,2]. For most men, we suggest using a single fraction of 8 Gy to the involved area. Thebenefits of radiation therapy (RT) in this setting, a discussion of optimal treatment schedules(eg, single- versus multiple-fractionation RT), and the use of stereotactic body radiotherapy asan alternative to EBRT are discussed separately. (See "Radiation therapy for the management ofpainful bone metastases".)Bone-targeted radioisotopes — Ra-223, an alpha particle-emitting agent, is the onlyradiopharmaceutical that prolongs overall survival and decreases symptomatic SREs inappropriately selected men with CRPC. Beta particle-emitting radioisotopes, such as strontium-89 and samarium-153 ethylenediamine tetramethylene phosphonate, may provide palliation ofpain, but they do not significantly prolong overall survival. (See 'Radium-223' below and 'Betaemittingradioisotopes' below.)These radioisotopes, which vary in their physical properties ( table 2), are mainly used in menwith advanced prostate cancer who are symptomatic from multiple osteoblastic bonemetastases. A prerequisite for bone-targeted radioisotope treatment is the presence of uptakeon bone scan due to metastatic disease at the sites that correlate with pain.Radium-223 — For men with symptomatic metastatic CRPC and bone pain who havepredominantly bony metastases and no evidence of visceral or large nodal metastases, Ra-223is an option to reduce symptomatic SREs (including bone pain) and improve health-relatedquality of life. A beneficial role for combinations of Ra-223 with systemic therapy has not beenestablished, and at least some data suggest detrimental outcomes when Ra-223 is combinedwith abiraterone. We suggest against initiating Ra-223 and abiraterone at the same time. Ra-https://www.uptodate.com/contents/17128/print 3/27
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Bone metastases in advanced prostate cancer. Management

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