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Hormone Therapy and Castration Resistance of Prostate Cancer pp 317–325Cite as

Bone-Targeted Treatment in CRPC Management

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Abstract

Prostate cancer frequently metastasizes to bone, and progression of advanced prostate cancer is parallel to progression of bone metastases. Metastatic bone disease often causes skeletal-related events (SREs). SREs lead to deterioration of patients’ quality of life and even their prognosis. SREs also have significant impacts on health resource utilization and financial burden. Ironically, androgen deprivation therapy (ADT) itself induces osteoporosis and may affect the incidence of SREs. Thus, preventing SREs is considered as one of major issues in the management of patients with prostate cancer and bone metastases, and bone-targeted treatment combined with systemic therapy against prostate cancer is a rational approach.

The usefulness of zoledronic acid and denosumab has been established for the prevention of SREs in men with CRPC and bone metastases. These agents are also proved to be effective for the prevention of ADT-induced bone loss. Alpha-emitter radium-223 demonstrates a survival benefit as well as a preventive effect for SSEs in men with bony metastatic CRPC patients without visceral metastases. The survival benefit or SRE-preventive effect of bisphosphonates or denosumab for men with CSPC is controversial and routine use of these agents for these purposes is not currently recommended. Bone-metastasis-directed SBRT is a new and aggressive treatment approach for patients with oligometastatic prostate cancer recurrence, but is still under investigation.

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References

  1. Inoue T, Segawa T, Kamba T, Yoshimura K, Nakamura E, Nishiyama H, et al. Prevalence of skeletal complications and their impact on survival of hormone refractory prostate cancer patients in Japan. Urology. 2009;73:1104–9. https://doi.org/10.1016/j.urology.2008.07.062.

    Article  PubMed  Google Scholar 

  2. Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26:1148–59. https://doi.org/10.1200/JCO.2007.12.4487.

    Article  PubMed  Google Scholar 

  3. Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31:578–83.

    Article  CAS  PubMed  Google Scholar 

  4. Nørgaard M, Jensen AØ, Jacobsen JB, Cetin K, Fryzek JP, Sørensen HT. Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007). J Urol. 2010;184:162–7. https://doi.org/10.1016/j.juro.2010.03.034.

    Article  PubMed  Google Scholar 

  5. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, 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;96:879–82.

    Article  CAS  PubMed  Google Scholar 

  6. Weinfurt KP, Li Y, Castel LD, Saad F, Timbie JW, Glendenning GA, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol. 2005;16:579–84.

    Article  CAS  PubMed  Google Scholar 

  7. DePuy V, Anstrom KJ, Castel LD, Schulman KA, Weinfurt KP, Saad F. Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer. Support Care Cancer. 2007;15:869–76.

    Article  PubMed  Google Scholar 

  8. Sathiakumar N, Delzell E, Morrisey MA, Falkson C, Yong M, Chia V, et al. Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999-2006. Prostate Cancer Prostatic Dis. 2011;14:177–83. https://doi.org/10.1038/pcan.2011.7.

    Article  CAS  PubMed  Google Scholar 

  9. Bahl A, Hoefeler H, Duran I, Hechmati G, Garzon-Rodriguez C, Ashcroft J, et al. Health resource utilization associated with skeletal-related events in patients with advanced prostate cancer: a European subgroup analysis from an observational, multinational study. J Clin Med. 2014;3:883–96. https://doi.org/10.3390/jcm3030883.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hagiwara M, Delea TE, Saville MW, Chung K. Healthcare utilization and costs associated with skeletal-related events in prostate cancer patients with bone metastases. Prostate Cancer Prostatic Dis. 2013;16:23–7. https://doi.org/10.1038/pcan.2012.42.

    Article  CAS  PubMed  Google Scholar 

  11. Krupski TL, Foley KA, Baser O, Long S, Macarios D, Litwin MS. Health care cost associated with prostate cancer, androgen deprivation therapy and bone complications. J Urol. 2007;178:1423–8.

    Article  PubMed  Google Scholar 

  12. Morote J, Morin JP, Orsola A, Abascal JM, Salvador C, Trilla E, et al. Prevalence of osteoporosis during long-term androgen deprivation therapy in patients with prostate cancer. Urology. 2007;69:500–4.

    Article  PubMed  Google Scholar 

  13. Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005;352:154–64.

    Article  CAS  PubMed  Google Scholar 

  14. Oefelein MG, Ricchiuti V, Conrad W, Resnick MI. Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol. 2002;168:1005–7.

    Article  PubMed  Google Scholar 

  15. Bienz M, Saad F. Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review. Bonekey Rep. 2015;4:716. https://doi.org/10.1038/bonekey.2015.85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol. 2003;169:2008–12.

    Article  CAS  PubMed  Google Scholar 

  17. Michaelson MD, Kaufman DS, Lee H, McGovern FJ, Kantoff PW, Fallon MA, 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;25:1038–42.

    Article  CAS  PubMed  Google Scholar 

  18. Satoh T, Kimura M, Matsumoto K, Tabata K, Okusa H, Bessho H, et al. Single infusion of zoledronic acid to prevent androgen deprivation therapy-induced bone loss in men with hormone-naive prostate carcinoma. Cancer. 2009;115:3468–74. https://doi.org/10.1002/cncr.24404.

    Article  CAS  PubMed  Google Scholar 

  19. Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361:745–55. https://doi.org/10.1056/NEJMoa0809003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vignani F, Bertaglia V, Buttigliero C, Tucci M, Scagliotti GV, Di Mario M. Skeletal metastases and impact of anticancer and bone-targeted agents in patients with castration-resistant prostate cancer. Cancer Treat Rev. 2016;44:61–73. https://doi.org/10.1016/j.ctrv.2016.02.002.

    Article  CAS  PubMed  Google Scholar 

  21. James ND, Pirrie SJ, Pope AM, Barton D, Andronis L, Goranitis I, et al. Clinical outcome 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;2:493–9. https://doi.org/10.1001/jamaoncol.2015.5570.

    Article  PubMed  Google Scholar 

  22. Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, et al. Effect of longer-interval vs standard dosing of zoledronic acid on skeletal events in patients with bone metastases: a randomized clinical trial. JAMA. 2017;317:48–58. https://doi.org/10.1001/jama.2016.19425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dearnaley DP, Sydes MR, Mason MD, Stott M, Powell CS, Robinson AC, 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;95:1300–11.

    Article  CAS  PubMed  Google Scholar 

  24. Smith MR, Halabi S, Ryan CJ, Hussain A, Vogelzang N, Stadler W, 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;32:1143–50. https://doi.org/10.1200/JCO.2013.51.6500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–77. https://doi.org/10.1016/S0140-6736(15)01037-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kamba T, Kamoto T, Maruo S, Kikuchi T, Shimizu Y, Namiki S, et al. A phase III multicenter, randomized, controlled study of combined androgen blockade with versus without zoledronic acid in prostate cancer patients with metastatic bone disease: results of the ZAPCA trial. Int J Clin Oncol. 2017;22:166–73. https://doi.org/10.1007/s10147-016-1037-2.

    Article  CAS  PubMed  Google Scholar 

  27. Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, et al. Denosumabu versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377:813–22. https://doi.org/10.1016/S0140-6736(10)62344-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Smith MR, Coleman RE, Klotz L, Pittman K, Milecki P, Ng S, et al. Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events. Ann Oncol. 2015;26:368–74. https://doi.org/10.1093/annonc/mdu519.

    Article  CAS  PubMed  Google Scholar 

  29. Jong JM, Oprea-Lager DE, Hooft L, de Klerk JM, Bloemendal HJ, Verheul HM, et al. Radiopharmaceuticals for palliation of bone pain in patients with castration-resistant prostate cancer metastatic to bone: a systematic review. Eur Urol. 2016;70:416–26. https://doi.org/10.1016/j.eururo.2015.09.005.

    Article  PubMed  Google Scholar 

  30. Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, 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;15:738–46. https://doi.org/10.1016/S1470-2045(14)70183-4.

    Article  CAS  PubMed  Google Scholar 

  31. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002;94:1458–68.

    Article  CAS  PubMed  Google Scholar 

  32. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23. https://doi.org/10.1056/NEJMoa1213755.

    Article  CAS  PubMed  Google Scholar 

  33. Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, 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;379:39–46. https://doi.org/10.1016/S0140-6736(11)61226-9.

    Article  CAS  PubMed  Google Scholar 

  34. Dearnaley DP, Mason MD, Parmar MK, Sanders K, Sydes MR. Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials. Lancet Oncol. 2009;10:872–6. https://doi.org/10.1016/S1470-2450(09)70201-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wirth M, Tammela T, Cicalese V, Gomez Veiga F, Delaere K, Miller K, et al. Prevention of bone metastases in patients with high-risk non metastatic prostate cancer treated with zoledronic acid: efficacy and safety results of the Zometa European Study (ZEUS). Eur Urol. 2015;67:482–91. https://doi.org/10.1016/j.eururo.2014.02.014.

    Article  CAS  PubMed  Google Scholar 

  36. Tosoian JJ, Gorin MA, Ross AE, Pienta KJ, Tran PT, Schaeffer EM. Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations. Nat Rev Urol. 2017;14:15–25. https://doi.org/10.1038/nrurol.2016.175.

    Article  CAS  PubMed  Google Scholar 

  37. Ost P, Jereczek-Fossa BA, As NV, Zilli T, Muacevic A, Olivier K, et al. Progression-free survival following stereotactic body radiotherapy for oligometastatic prostate cancer treatment-naive recurrence: a multi-institutional analysis. Eur Urol. 2016;69:9–12. https://doi.org/10.1016/j.eururo.2015.07.004.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan

    Tomomi Kamba M.D., Ph.D.

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  1. Tomomi Kamba M.D., Ph.D.
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Correspondence to Tomomi Kamba M.D., Ph.D. .

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Editors and Affiliations

  1. Department of Urology, Tohoku University School of Medicine, Sendai, Japan

    Yoichi Arai

  2. Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Osamu Ogawa

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Kamba, T. (2018). Bone-Targeted Treatment in CRPC Management. In: Arai, Y., Ogawa, O. (eds) Hormone Therapy and Castration Resistance of Prostate Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-10-7013-6_32

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  • DOI: https://doi.org/10.1007/978-981-10-7013-6_32

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