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Bone metastases in advanced prostate cancer: Management

Authors
A Oliver Sartor, MD
Steven J DiBiase, MD
Section Editors
Nicholas Vogelzang, MD
W Robert Lee, MD, MS, MEd
Jerome P Richie, MD, FACS
Deputy Editor
Michael E Ross, MD

INTRODUCTION

The clinical manifestations of prostate cancer at diagnosis have changed substantially since the introduction of prostate specific antigen (PSA) screening. Although a higher percentage of men have localized disease at presentation, metastatic prostate cancer remains an important clinical problem, in terms of the number of men with advanced disease, its impact on quality of life and as a cause of mortality.

Osteoblastic lesions in bone are the most common site of metastasis. These frequently are symptomatic, and can cause pain, debility, and functional impairment. The treatment of bone metastases in men with prostate cancer is palliative. The goals of treatment are to improve survival, relieve pain, improve mobility, and prevent complications (eg, pathologic fractures, epidural spinal cord compression).

The management of bone metastases in men with advanced prostate cancer is reviewed here. Treatment can include treatments directed specifically against the cancer involving bone, osteoclast inhibition to prevent complications from osseous involvement, and systemic therapy directed against the cancer.

The clinical presentation and evaluation of bone metastases and the overall approach to the management of men with advanced prostate cancer are discussed separately. (See "Overview of the epidemiology, clinical presentation, diagnosis, and management of adult patients with bone metastasis" and "Bone metastases in advanced prostate cancer: Clinical manifestations and diagnosis" and "Overview of the treatment of disseminated prostate cancer".)

TREATMENT OF PATIENTS WITH SYMPTOMATIC BONE METASTASES

External beam radiation therapy — External beam radiation therapy (RT) is the treatment of choice for men with castration resistant prostate cancer and bone pain that is limited to one or a limited number of sites. External beam RT is discussed separately. (See "Radiation therapy for the management of painful bone metastases".)

                        

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Literature review current through: Nov 2016. | This topic last updated: Thu Aug 04 00:00:00 GMT 2016.
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References
Top
  1. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013; 369:213.
  2. Sartor O, Coleman R, Nilsson S, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol 2014; 15:738.
  3. Nilsson S, Vogelzang N, Sartor AO, et al. 1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase 3 ALSYMPCA study (abstract). American Society of Clinical Oncology Genitourinary Cancer Symposium 2014.
  4. Hoskin P, Sartor O, O'Sullivan JM, et al. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol 2014; 15:1397.
  5. Saad F, Carles J, Gillessen S, et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol 2016.
  6. Etchebehere EC, Milton DR, Araujo JC, et al. Factors affecting (223)Ra therapy: clinical experience after 532 cycles from a single institution. Eur J Nucl Med Mol Imaging 2016; 43:8.
  7. Morris MJ, Higano CS, Scher HI, et al. Effects of radium-223 dichloride (Ra-223) with docetaxel (D) versus D on prostate-specific antigen (PSA) and bone alkaline phosphatase (bALP) in patients (pts) with castration-resistant prostate cancer (CRPC) and bone metastases (mets): A phase 1/2a clinical trial (abstract). J Clin Oncol 33, 2015 (suppl 7; abstr 202).
  8. Roqué M, Martinez MJ, Alonso P, et al. Radioisotopes for metastatic bone pain. Cochrane Database Syst Rev 2003; :CD003347.
  9. Liepe K, Kotzerke J. A comparative study of 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr in the treatment of painful skeletal metastases. Nucl Med Commun 2007; 28:623.
  10. Lewington VJ, McEwan AJ, Ackery DM, et al. A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone. Eur J Cancer 1991; 27:954.
  11. Buchali K, Correns HJ, Schuerer M, et al. Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma. Eur J Nucl Med 1988; 14:349.
  12. Porter AT, McEwan AJ, Powe JE, et al. Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys 1993; 25:805.
  13. Quilty PM, Kirk D, Bolger JJ, et al. A comparison of the palliative effects of strontium-89 and external beam radiotherapy in metastatic prostate cancer. Radiother Oncol 1994; 31:33.
  14. Oosterhof GO, Roberts JT, de Reijke TM, et al. Strontium(89) chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer, Genitourinary Group. Eur Urol 2003; 44:519.
  15. James ND, Pirrie SJ, Pope AM, et al. Clinical Outcomes and Survival Following Treatment of Metastatic Castrate-Refractory Prostate Cancer With Docetaxel Alone or With Strontium-89, Zoledronic Acid, or Both: The TRAPEZE Randomized Clinical Trial. JAMA Oncol 2016; 2:493.
  16. Serafini AN, Houston SJ, Resche I, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. J Clin Oncol 1998; 16:1574.
  17. Sartor O, Reid RH, Hoskin PJ, et al. Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 2004; 63:940.
  18. Hoskin P, Sundar S, Reczko K, et al. A Multicenter Randomized Trial of Ibandronate Compared With Single-Dose Radiotherapy for Localized Metastatic Bone Pain in Prostate Cancer. J Natl Cancer Inst 2015; 107.
  19. http://www.insightec.com/Prostate-Cancer-Research.html.
  20. Hurwitz MD, Ghanouni P, Kanaev SV, et al. Magnetic resonance-guided focused ultrasound for patients with painful bone metastases: phase III trial results. J Natl Cancer Inst 2014; 106.
  21. Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002; 94:1458.
  22. Saad F, Gleason DM, Murray R, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004; 96:879.
  23. Costa L, Major PP. Effect of bisphosphonates on pain and quality of life in patients with bone metastases. Nat Clin Pract Oncol 2009; 6:163.
  24. Heidenreich A, Hofmann R, Engelmann UH. The use of bisphosphonate for the palliative treatment of painful bone metastasis due to hormone refractory prostate cancer. J Urol 2001; 165:136.
  25. Rodrigues P, Hering F, Campagnari JC. Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients. Prostate Cancer Prostatic Dis 2004; 7:350.
  26. Hering F, Rodrigues PR, Lipay M. Clodronate for treatment of bone metastases in hormone refractory prostate cancer. Int Braz J Urol 2003; 29:228.
  27. Small EJ, Smith MR, Seaman JJ, et al. Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. J Clin Oncol 2003; 21:4277.
  28. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011; 377:813.
  29. http://pi.amgen.com/united_states/xgeva/xgeva_pi.pdf (Accessed on February 03, 2014).
  30. Smith MR, Halabi S, Ryan CJ, et al. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol 2014; 32:1143.
  31. Wirth M, Tammela T, Cicalese V, et al. Prevention of bone metastases in patients with high-risk nonmetastatic prostate cancer treated with zoledronic acid: efficacy and safety results of the Zometa European Study (ZEUS). Eur Urol 2015; 67:482.
  32. Mason MD, Sydes MR, Glaholm J, et al. Oral sodium clodronate for nonmetastatic prostate cancer--results of a randomized double-blind placebo-controlled trial: Medical Research Council PR04 (ISRCTN61384873). J Natl Cancer Inst 2007; 99:765.
  33. Smith MR, Saad F, Coleman R, et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 2012; 379:39.
  34. Smith MR, Saad F, Oudard S, et al. Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J Clin Oncol 2013; 31:3800.
  35. Clarke NW. Balancing toxicity and efficacy: learning from trials and treatment using antiresorptive therapy in prostate cancer. Eur Urol 2014; 65:287.
  36. Gartrell BA, Coleman RE, Fizazi K, et al. Toxicities following treatment with bisphosphonates and receptor activator of nuclear factor-κB ligand inhibitors in patients with advanced prostate cancer. Eur Urol 2014; 65:278.