Urologic Oncology: Seminars and Original Investigations
Volume 27, Issue 6, Supplement , Pages S1-S20 , November 2009

New opportunities in the management of prostate cancer–related bone complications

Received 11 June 2009 ,Revised 31 July 2009 ,Accepted 3 August 2009.

References 

  1. Saad F, Clarke N, Colombel M. Natural history and treatment of bone complications in prostate cancer. Eur Urol. 2006;49:429–440
  2. Saad F, McKiernan J, Eastham J. Rationale for zoledronic acid therapy in men with hormone-sensitive prostate cancer with or without bone metastasis. Urol Oncol. 2006;24:4–12
  3. Saad F. The role of bisphosphonates in the management of prostate cancer. Curr Oncol Rep. 2006;8:221–227
  4. Higano CS. Understanding treatments for bone loss and bone metastases in patients with prostate cancer: A practical review and guide for the clinician. Urol Clin North Am. 2004;31:331–352
  5. Smith MR, Kabbinavar F, Saad F, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23:2918–2925
  6. Bradley DA, Hussain M, Dipaola RS, et al. Bone directed therapies for prostate cancer. J Urol. 2007;178:S42–S48
  7. Vessella RL, Corey E. Targeting factors involved in bone remodeling as treatment strategies in prostate cancer bone metastasis. Clin Cancer Res. 2006;12:6285s–6290s
  8. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;71–96
  9. Greene KL, Cowan JE, Cooperberg MR, et al. Who is the average patient presenting with prostate cancer?. Urology. 2005;66:76–82
  10. Ward JF, Slezak JM, Blute ML, et al. Radical prostatectomy for clinically advanced (cT3) prostate cancer since the advent of prostate-specific antigen testing: 15-year outcome. BJU Int. 2005;95:751–756
  11. Nam RK, Jewett MA, Krahn MD. Prostate cancer: 2. Natural history. CMAJ. 1998;159:685–691
  12. Han M, Partin AW, Pound CR, et al. Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy (The 15-year Johns Hopkins experience). Urol Clin North Am. 2001;28:555–565
  13. Kuban DA, Thames HD, Levy LB, et al. Long-term multi-institutional analysis of stage T1–T2 prostate cancer treated with radiotherapy in the PSA era. Int J Radiat Oncol Biol Phys. 2003;57:915–928
  14. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–1512
  15. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513–1520
  16. Nelson JB, Love W, Chin JL, et al. phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer. 2008;113:2478–2487
  17. Ryan CJ, Elkin EP, Cowan J, et al. Initial treatment patterns and outcome of contemporary prostate cancer patients with bone metastases at initial presentation: Data from CaPSURE. Cancer. 2007;110:81–86
  18. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12:6243s–6249s
  19. Eisenberger MA, Blumenstein BA, Crawford ED, et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med. 1998;339:1036–1042
  20. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591–1597
  21. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80:1588–4
  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;96:879–882
  23. 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;94:1458–1468
  24. Cook RJ, Coleman R, Brown J, et al. Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. Clin Cancer Res. 2006;12:3361–3367
  25. Brown JE, Cook RJ, Major P, et al. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005;97:59–69
  26. Coleman RE, Major P, Lipton A, et al. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid. J Clin Oncol. 2005;23:4925–4935
  27. Rubin MA, Putzi M, Mucci N, et al. Rapid (“warm”) autopsy study for procurement of metastatic prostate cancer. Clin Cancer Res. 2000;6:1038–1045
  28. Rigaud J, Tiguert R, Le NL, et al. Prognostic value of bone scan in patients with metastatic prostate cancer treated initially with androgen deprivation therapy. J Urol. 2002;168:1423–1426
  29. Kiebzak GM, Beinart GA, Perser K, Ambrose CG, Siff SJ, Heggeness MH. Undertreatment of osteoporosis in men with hip fracture. Arch Intern Med. 2002;162:2217–2222
  30. Weinfurt KP, Li Y, Castel LD, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol. 2005;16:579–584
  31. Oefelein MG, Ricchiuti V, Conrad W, et al. Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol. 2002;168:1005–1007
  32. Krupski TL, Foley KA, Baser O, et al. Health care cost associated with prostate cancer, androgen deprivation therapy and bone complications. J Urol. 2007;178:1423–1428
  33. Groot MT, Boeken Kruger CG, Pelger RC, Uyl-de Groot CA. Costs of prostate cancer, metastatic to the bone, in the Netherlands. Eur Urol. 2003;43:226–232
  34. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350:1655–1664
  35. Lipton A. Future treatment of bone metastases. Clin Cancer Res. 2006;12:6305s–6308s
  36. Mundy GR. Metastasis to bone: Causes, consequences, and therapeutic opportunities. Nat Rev Cancer. 2002;2:584–593
  37. Clines GA, Guise TA. Molecular mechanisms and treatment of bone metastasis. Expert Rev Mol Med. 2008;10:e7;1–3
  38. Chen G, Sircar K, Aprikian A, et al. Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation. Cancer. 2006;107:289–298
  39. Selvaggi G, Scagliotti GV. Management of bone metastases in cancer: A review. Crit Rev Oncol Hematol. 2005;56:365–378
  40. Lecouvet FE, Geukens D, Stainier A, et al. Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: Diagnostic and cost-effectiveness and comparison with current detection strategies. J Clin Oncol. 2007;25:3281–3287
  41. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Prostate cancer. 2009;V. 2.2009
  42. Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med. 1998;338:736–746
  43. Eastham JA. Bone health in men receiving androgen deprivation therapy for prostate cancer. J Urol. 2007;177:17–24
  44. Dawson-Hughes B. A revised clinician's guide to the prevention and treatment of osteoporosis. J Clin Endocrinol Metab. 2008;93:2463–2465
  45. Israeli RS, Ryan CW, Jung LL. Managing bone loss in men with locally advanced prostate cancer receiving androgen deprivation therapy. J Urol. 2008;179:414–423
  46. Lipton A, Cook R, Saad F, et al. Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid. Cancer. 2008;113:193–201
  47. Saad F, Cook RJ, Lipton A, et al. Correlations between N-telopeptide of type I collagen response and zoledronic acid on clinical outcomes in patients with bone metastases from prostate cancer. Proceedings of the 2008 American Urological Association Annual Meeting. Orlando, (FL), May, 2008. Presentation 519.
  48. Berenson JR, Rajdev L, Broder M. Managing bone complications of solid tumors. Cancer Biol Ther. 2006;5:1086–1089
  49. Bartels RH, van der Linden YM, van der Graaf WT. Spinal extradural metastasis: Review of current treatment options. CA Cancer J Clin. 2008;58:245–259
  50. Smith MR. Bisphosphonates to prevent skeletal complications in men with metastatic prostate cancer. J Urol. 2003;170:S55–S57
  51. 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;21:4277–4284
  52. Dearnaley DP, Sydes MR, Mason MD, et al. A double-blind, placebo-controlled, randomized trial of oral sodium clodronate for metastatic prostate cancer (MRC PR05 Trial). J Natl Cancer Inst. 2003;95:1300–1311
  53. Ernst DS, Tannock IF, Winquist EW, et al. Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone and placebo in patients with hormone-refractory prostate cancer and pain. J Clin Oncol. 2003;21:3335–3342
  54. Smith MR. Osteoclast targeted therapy for prostate cancer: Bisphosphonates and beyond. Urol Oncol. 2008;26:420–425
  55. Smith MR, Bhoopalam N, Sweeney C, et al. phase III randomized study of zoledronate for the prevention of skeletal-related events in patients with prostate cancer and bone metastases undergoing androgen deprivation therapy (National Cancer Institute, 2009). http://clinicaltrials.gov/ct2/show/NCT00079001
  56. Berenson JR. Recommendations for zoledronic acid treatment of patients with bone metastases. Oncologist. 2005;10:52–62
  57. Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22:1479–1491
  58. Badros A, Weikel D, Salama A, et al. Osteonecrosis of the jaw in multiple myeloma patients: Clinical features and risk factors. J Clin Oncol. 2006;24:945–952
  59. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: Bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144:753–761
  60. Badros A, Evangelos T, Goloubeva O, et al. Long-term follow-up of multiple myeloma (mm) patients (pts) with osteonecrosis of the jaw (ONJ). Blood. 2007;110:3519;[Abstract]
  61. Mason MD. Development of bone metastases from prostate cancer: First results of the MRC PR04 trial (ISCRTN 61384873), 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol. 2004;22:4511
  62. Effectiveness of zoledronic acid treatment for the prevention of bone metastases in high risk prostate cancer patients (A randomized, open-label, multicenter study of the European Association of Urology (EAU) in Cooperation with the Scandinavian Prostate Cancer Group (SPCG) and the Arbeitsgemeinschaft Urologische Onkologie (AUO). Protocol No. CZOL446G DE08. Current Controlled Trials, 2009). http://www.controlled-trials.com/ISRCTN66626762/zeus
  63. Petrut B, Simmons C, Broom R, et al. Pharmacotherapy of bone metastases in breast cancer patients. Expert Opin Pharmacother. 2008;9:937–945
  64. Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19:1059–1066
  65. Peterson MC, Stouch BJ, Chen D, et al. AMG 162 maintains serum concentrations for up to 9 months following a single subcutaneous dose in healthy postmenopausal women. J Bone Miner Res. 2003;18:SA393
  66. Fizazi K, Lipton A, Mariette X, et al. Denosumab in patients with bone metastases from prostate, breast, and other cancers and elevated urinary N-telopeptide (uNTx) during intravenous bisphosphonate (IV BP) therapy: Final results of a randomized, phase II study. J Clin Oncol. 2008;26:3596;[Abstract]
  67. Fizazi K, Lipton A, Mariette X, et al. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009;27:1564–1571
  68. Amgen. Double-blind study of denosumab compared with zoledronic acid in the treatment of bone metastases in men with hormone-refractory prostate cancer. clinicaltrials gov, 2009 http://clinicaltrials.gov/ct2/show/NCT00321620?term=denosumab+prostate+cancer&rank=2
  69. Amgen. Study on prolonging bone metastasis-free survival in men with hormone refractory prostate cancer. clinicaltrials gov, 2009 http://clinicaltrials.gov/ct2/show/NCT00286091?term=denosumab+prostate+cancer&rank=5
  70. McClung M, Bone H, Cosman F, et al. A randomized, double-blind, placebo-controlled study of odanacatib (MK-822) in the treatment of postmenopausal women with low bone mineral density: 24-month results. Proceedings of the American Society for Bone and Mineral Research 30th Annual Meeting. Montreal, Quebec, Canada, September 2008. Presentation 1291.
  71. Jensen AB, Olmeo N, Wynne C, et al. Effect of cathepsin k inhibition on suppression of bone resorption in women with breast cancer and established bone metastases in a 4-week, double-blind, randomized controlled trial. J Clin Oncol. 2008;26:1023;[Abstract]
  72. Engleman VW, Nickols GA, Ross FP, et al. A peptidomimetic antagonist of the α(v)β3 integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo. J Clin Invest. 1997;99:2284–2292
  73. Marzia M, Sims NA, Voit S, et al. Decreased c-Src expression enhances osteoblast differentiation and bone formation. J Cell Biol. 2000;151:311–320
  74. Rucci N, Susa M, Teti A. Inhibition of protein kinase c-Src as a therapeutic approach for cancer and bone metastases. Anticancer Agents Med Chem. 2008;8:342–349
  75. Nelson JB, Nabulsi AA, Vogelzang NJ, et al. Suppression of prostate cancer induced bone remodeling by the endothelin receptor A antagonist atrasentan. J Urol. 2003;169:1143–1149
  76. Carducci MA, Saad F, Abrahamsson PA, et al. A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer. 2007;110:1959–1966
  77. Michaelson MD, Kaufman DS, Kantoff P, et al. Randomized phase II study of atrasentan alone or in combination with zoledronic acid in men with metastatic prostate cancer. Cancer. 2006;107:530–535
  78. Dawson N, Phung D, Morris T, et al. Impact of the specific endothelin A receptor antagonist ZD4054 on overall survival and bone metastasis in patients with normone-resistant prostate cancer: Results of a phase II trial. Proceedings of the 2008 Genitourinary Cancers Symposium. Orlando, (FL), January, 2008. Presentation 7.
  79. AstraZeneca. A phase III trial of ZD4054 (endothelin A antagonist) in non-metastatic hormone resistant prostate cancer (ENTHUSE M0). clinicaltrials gov, 2009 http://clinicaltrials.gov/ct2/show/NCT00626548
  80. AstraZeneca. A phase III trial of ZD4054 (endothelin A antagonist) in hormone resistant prostate cancer with bone metastases (ENTHUSE M1). clinicaltrials gov, 2009 http://clinicaltrials.gov/ct2/show/NCT00554229?intr=%22ZD4054%22&rank=3
  81. AstraZeneca. A phase III trial of ZD4054 (endothelin A antagonist) and docetaxel in metastatic hormone resistant prostate cancer (ENTHUSEM1C). clinicaltrials gov, 2009 http://clinicaltrials.gov/ct2/show/NCT00617669?intr=%22ZD4054%22&rank=11
  82. Tian E, Zhan F, Walker R, et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med. 2003;349:2483–2494
  83. Oshima T, Abe M, Asano J, et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood. 2005;106:3160–3165
  84. Yaccoby S, Ling W, Zhan F, et al. Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood. 2007;109:2106–2111
  85. Bandyopadhyay A, Agyin JK, Wang L, et al. Inhibition of pulmonary and skeletal metastasis by a transforming growth factor-beta type I receptor kinase inhibitor. Cancer Res. 2006;66:6714–6721
  86. Brown SA, Guise TA. Cancer-associated bone disease. Curr Osteoporos Rep. 2007;5:120–127
  87. Khosla S, Melton LJ, Atkinson EJ, et al. Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinol Metab. 2001;86:3555–3561
  88. Kaufman JM, Johnell O, Abadie E, et al. Background for studies on the treatment of male osteoporosis: State of the art. Ann Rheum Dis. 2000;59:765–772
  89. Melton LJ, Chrischilles EA, Cooper C, et al. Perspective (How many women have osteoporosis?). J Bone Miner Res. 1992;7:1005–1010
  90. Smith MR, McGovern FJ, Fallon MA, et al. Low bone mineral density in hormone-naive men with prostate carcinoma. Cancer. 2001;91:2238–2245
  91. Barry MJ, Delorenzo MA, Walker-Corkery ES, et al. The rising prevalence of androgen deprivation among older American men since the advent of prostate-specific antigen testing: A population-based cohort study. BJU Int. 2006;98:973–978
  92. Mittan D, Lee S, Miller E, et al. Bone loss following hypogonadism in men with prostate cancer treated with GnRH analogs. J Clin Endocrinol Metab. 2002;87:3656–3661
  93. Daniell HW. Osteoporosis after orchiectomy for prostate cancer. J Urol. 1997;157:439–444
  94. Shahinian VB, Kuo YF, Freeman JL, et al. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005;352:154–164
  95. Smith MR, Lee WC, Brandman J, et al. Gonadotropin-releasing hormone agonists and fracture risk: A claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol. 2005;23:7897–7903
  96. Guise TA. Bone loss and fracture risk associated with cancer therapy. Oncologist. 2006;11:1121–1131
  97. Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int. 2005;16:581–589
  98. Diamond TH, Higano CS, Smith MR, et al. Osteoporosis in men with prostate carcinoma receiving androgen-deprivation therapy: Recommendations for diagnosis and therapies. Cancer. 2004;100:892–899
  99. Bone and Cancer Foundation. Vitamin D deficiency: Information for cancer patients (Bone and Cancer Foundation, 2008). http://www.boneandcancerfoundation.org/pdfs/Vitamin_D_Booklet.pdf
  100. Greenspan SL, Nelson JB, Trump DL, et al. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: A randomized trial. Ann Intern Med. 2007;146:416–424
  101. Smith MR, McGovern FJ, Zietman AL, et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med. 2001;345:948–955
  102. Smith MR, Eastham J, Gleason DM, et al. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol. 2003;169:2008–2012
  103. Ryan CW, Huo D, Demers LM, et al. Zoledronic acid initiated during the first year of androgen deprivation therapy increases bone mineral density in patients with prostate cancer. J Urol. 2006;176:972–978
  104. Michaelson MD, Kaufman DS, Lee H, et al. Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer. J Clin Oncol. 2007;25:1038–1042
  105. Smith MR, Fallon MA, Lee H, et al. Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: A randomized controlled trial. J Clin Endocrinol Metab. 2004;89:3841–3846
  106. Smith MR, Malkowicz SB, Chu F, et al. Toremifene increases bone mineral density in men receiving androgen deprivation therapy for prostate cancer: Interim analysis of a multicenter phase 3 clinical study. J Urol. 2008;179:152–155
  107. Amgen. AMG 162 in the treatment of bone loss in subjects undergoing androgen-deprivation therapy for non-metastatic prostate cancer. clinicaltrials gov, 2009 http://clinicaltrials.gov/ct2/show/NCT00089674?term=denosumab+prostate+cancer&rank=3
  108. Smith MR, Egerdie B, Hernández-Toriz N, et al. A randomized, double-blind, placebo-controlled trial of denosumab in men receiving androgen deprivation therapy for non-metastatic prostate cancer. Proceedings of the 24th Annual Congress of the European Association of Urology, 2009, http://www.uroweb.org/index.php?id=312&no_cache=1&AID=20975.

 Conflict of Interest: This CME activity is supported by an educational donation provided by Amgen.

 This CME-certified activity is based on information presented at a satellite symposium held on Friday, December 5, 2008, in Bethesda, Maryland, in conjunction with the 9th Annual Society of Urologic Oncology Winter Meeting.

 Sponsored by Curatio CME Institute.

PII: S1078-1439(09)00238-5

doi: 10.1016/j.urolonc.2009.08.004

Urologic Oncology: Seminars and Original Investigations
Volume 27, Issue 6, Supplement , Pages S1-S20 , November 2009

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