Skip to main content

Advertisement

SpringerLink
Log in

Management of Metastatic Hormone-Sensitive Prostate Cancer

  • Prostate Cancer (A Kibel, Section Editor)
  • Published:
Current Urology Reports Aims and scope Submit manuscript

Abstract

In 2014, prostate cancer will affect roughly 15 % of American men during their lifetimes with about 230,000 new cases and 29,000 deaths per year. If required, most can be treated with curative surgery or radiotherapy. Upon relapse, androgen deprivation therapy (intermittent or continuous) is the cornerstone of treatment for hormone-sensitive disease. Response is variable and treatment is associated with a significant risk of toxicity. Recently, significant advances in survival have been demonstrated with chemohormonal therapy in men with high-volume disease. In addition, new findings have informed the approach to preventing bone complications in patients on therapy for metastatic hormone-sensitive prostate cancer. Devising clinical prediction tools and biomarkers is needed to select patients most likely to benefit from certain therapies and allow for a personalized approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. SEER cancer statistics factsheets: prostate cancer. National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/statfacts/html/prost.html. Updated 2014. Accessed October/24, 2014.

  2. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367(3):203–13. doi:10.1056/NEJMoa1113162. This study confirmed watchful waiting as an appropriate alternative strategy to radical prostatectomy in men with low risk prostate cancer diagnosed by PSA screening. Therefore, elderly men with low risk, localized prostate cancer may be spared the associated morbidity, cost, and morality risk of surgery.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65(2):467–79. doi:10.1016/j.eururo.2013.11.002.

    Article  CAS  PubMed  Google Scholar 

  4. Loblaw DA, Virgo KS, Nam R, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2007;25(12):1596–605.

    Article  CAS  PubMed  Google Scholar 

  5. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1(4):293–7.

    CAS  Google Scholar 

  6. Tangen CM, Hussain MH, Higano CS, et al. Improved overall survival trends of men with newly diagnosed M1 prostate cancer: a SWOG phase III trial experience (S8494, S8894 and S9346). J Urol. 2012;188(4):1164–9. doi:10.1016/j.juro.2012.06.046.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Millikan RE, Wen S, Pagliaro LC, et al. Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. J Clin Oncol. 2008;26(36):5936–42. doi:10.1200/JCO.2007.15.9830.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Eisenberger MA, Blumenstein BA, Crawford ED, et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med. 1998;339(15):1036–42. doi:10.1056/NEJM199810083391504.

    Article  CAS  PubMed  Google Scholar 

  9. Crook JM, O’Callaghan CJ, Duncan G, et al. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012;367(10):895–903. doi:10.1056/NEJMoa1201546. This trial was the first to demonstrate non-inferiority of intermittent androgen deprivation therapy compared to continuous androgen deprivation therapy with respect to overall survival in men with biochemical recurrence post-radiotherapy for localized prostate cancer. Thus, it justifies the use of intermittent androgen deprivation therapy as a means to minimize toxicity and cost in appropriately selected patients.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Hussain M, Tangen CM, Berry DL, et al. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013;368(14):1314–25. doi:10.1056/NEJMoa1212299. This study was inconclusive as to whether intermittent androgen deprivation therapy was non-inferior to continuous therapy in men with metastatic hormone-sensitive prostate cancer. Thus, no definitive recommendation can be made in the metastatic population. Bearing in mind the possibility of slight inferiority of intermittent therapy with respect to overall survival, quality of life was mildly better and may be a reasonable compromise in patients with bothersome side effects.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Gleave M. Prime time for intermittent androgen suppression. Eur Urol. 2014;66(2):240–2. doi:10.1016/j.eururo.2013.05.052.

    Article  PubMed  Google Scholar 

  12. Eggener S. Commentary on “intermittent versus continuous androgen deprivation in prostate cancer.” Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, Dawson NA, Donnelly BJ, Venner PM, Vaishampayan UN, Schellhammer PF, Quinn DI, Raghavan D, Ely B, Moinpour CM, Vogelzang NJ, Thompson IM Jr, University of Michigan, division of hematology/oncology, ann arbor, MI. N engl J med 2013; 368(14):1314–25. doi: 10.1056/NEJMoa1212299. Urol Oncol. 2014;32(6):936–937. doi: 10.1016/j.urolonc.2014.01.009.

  13. Silva FC, Silva FM, Goncalves F, et al. Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade: results from a randomised phase 3 study by the South European Uroncological Group. Eur Urol. 2014;66(2):232–9. doi:10.1016/j.eururo.2013.03.055.

    Article  CAS  Google Scholar 

  14. Botrel TE, Clark O, Dos Reis RB, et al. Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis. BMC Urol. 2014;14:9-2490–14-9. doi:10.1186/1471-2490-14-9.

    Article  Google Scholar 

  15. Klotz L, Boccon-Gibod L, Shore ND, et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008;102(11):1531–8. doi:10.1111/j.1464-410X.2008.08183.x.

    Article  CAS  PubMed  Google Scholar 

  16. Crawford ED, Shore ND, Moul JW, et al. Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix. Urology. 2014;83(5):1122–8. doi:10.1016/j.urology.2014.01.013.

    Article  PubMed  Google Scholar 

  17. Klotz L, Miller K, Crawford ED, et al. Disease control outcomes from analysis of pooled individual patient data from five comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone agonists. Eur Urol. 2014.

  18. Lee D, Porter J, Gladwell D, Brereton N, Nielsen SK. A cost-utility analysis of degarelix in the treatment of advanced hormone-dependent prostate cancer in the United Kingdom. J Med Econ. 2014;17(4):233–47. doi:10.3111/13696998.2014.893240.

    Article  PubMed  Google Scholar 

  19. Zuckerman JM, Eure G, Malcolm J, Currie L, Given R. Prospective evaluation of testosterone fluctuations during a transition of therapy from degarelix to leuprolide in patients on androgen deprivation therapy. Urology. 2014;83(3):670–4. doi:10.1016/j.urology.2013.10.036.

    Article  PubMed  Google Scholar 

  20. 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(15):1502–12.

    Article  CAS  PubMed  Google Scholar 

  21. 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(15):1513–20.

    Article  CAS  PubMed  Google Scholar 

  22. Sweeney C, Chen Y, Carducci MA, et al. Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): an ECOG-led phase III randomized trial. ASCO Meet Abstr. 2014;32(15_suppl):LBA2. Presented at the plenary session of the 2014 ASCO Annual Meeting, this trial showed an unprecedented survival advantage with the use of upfront chemohormonal therapy in patients with metastatic hormone-sensitive prostate cancer. Those with a high volume of disease derive the greatest benefit. These results were paradigm-shifting for the approach to patients with early metastatic prostate cancer.

    Google Scholar 

  23. Eigl BJ, Eggener SE, Baybik J, et al. Timing is everything: preclinical evidence supporting simultaneous rather than sequential chemohormonal therapy for prostate cancer. Clin Cancer Res. 2005;11(13):4905–11.

    Article  CAS  PubMed  Google Scholar 

  24. Kyprianou N. The fringe benefits of cloning cancer. Sci Transl Med. 2014;6(254):254fs36. doi:10.1126/scitranslmed.3010174.

    Article  PubMed  Google Scholar 

  25. NCCN clinical practice guidelines in oncology: prostate cancer version I.2015. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Updated 2014. Accessed October/28, 2014.

  26. Gravis G, Fizazi K, Joly F, et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(2):149–58. doi:10.1016/S1470-2045(12)70560-0. This manuscript was negative with respect to an overall survival advantage with chemohormonal therapy in metastatic hormone-sensitive prostate cancer. However, it demonstrated the prolonged survival that can be achieved with androgen deprivation alone compared to a study with a larger proportion of higher volume disease.

    Article  CAS  PubMed  Google Scholar 

  27. Glass TR, Tangen CM, Crawford ED, Thompson I. Metastatic carcinoma of the prostate: identifying prognostic groups using recursive partitioning. J Urol. 2003;169(1):164–9. doi:10.1097/01.ju.0000042482.18153.30.

    Article  CAS  PubMed  Google Scholar 

  28. McKay RR, Taplin ME, Choueiri TK. Optimizing bone health and minimizing skeletal morbidity in men with prostate cancer. Hematol Oncol Clin N Am. 2013;27(6):1261–83. doi:10.1016/j.hoc.2013.08.009. ix.

    Article  Google Scholar 

  29. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359–81. doi:10.1007/s00198-014-2794-2.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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(11):1143–50. doi:10.1200/JCO.2013.51.6500. This trial importantly addressed the question as to whether use of a bisphosphonate in metastatic hormone-sensitive prostate cancer reduces skeletal related events. While negative, it provided greater understanding of bone health in this population, and underscored a key difference between hormone-sensitive and castration-resistant disease.

    Article  CAS  PubMed  Google Scholar 

  31. Vitolins MZ, Griffin L, Tomlinson WV, et al. Randomized trial to assess the impact of venlafaxine and soy protein on hot flashes and quality of life in men with prostate cancer. J Clin Oncol. 2013;31(32):4092–8. doi:10.1200/JCO.2012.48.1432.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Gardner JR, Livingston PM, Fraser SF. Effects of exercise on treatment-related adverse effects for patients with prostate cancer receiving androgen-deprivation therapy: a systematic review. J Clin Oncol. 2014;32(4):335–46. doi:10.1200/JCO.2013.49.5523.

    Article  PubMed  Google Scholar 

  33. Nguyen PL, Alibhai SM, Basaria S, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2014.

  34. Jespersen CG, Norgaard M, Borre M. Androgen-deprivation therapy in treatment of prostate cancer and risk of myocardial infarction and stroke: a nationwide Danish population-based cohort study. Eur Urol. 2014;65(4):704–9. doi:10.1016/j.eururo.2013.02.002.

    Article  CAS  PubMed  Google Scholar 

  35. Nguyen PL, Je Y, Schutz FA, et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA. 2011;306(21):2359–66. doi:10.1001/jama.2011.1745.

    Article  CAS  PubMed  Google Scholar 

  36. Tombal B, Borre M, Rathenborg P, et al. Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. Lancet Oncol. 2014;15(6):592–600. doi:10.1016/S1470-2045(14)70129-9.

    Article  CAS  PubMed  Google Scholar 

  37. Attard G. Anti-androgen monotherapy for metastatic prostate cancer. Lancet Oncol. 2014;15(6):543–4. doi:10.1016/S1470-2045(14)70159-7.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Dr. Brandon Bernard declares no potential conflicts of interest. Dr. Christopher Sweeney is a consultant with compensation from Sanofi, Janssen Pharmaceutical Companies, BIND Therapeutics, Inc., Astellas Pharma, and Bayer.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Dana-Farber Cancer Institute, 450 Brookline Avenue, D1230, Boston, MA, 02215, USA

    Brandon Bernard & Christopher J. Sweeney

Authors
  1. Brandon Bernard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher J. Sweeney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christopher J. Sweeney.

Additional information

This article is part of the Topical Collection on Prostate Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bernard, B., Sweeney, C.J. Management of Metastatic Hormone-Sensitive Prostate Cancer. Curr Urol Rep 16, 14 (2015). https://doi.org/10.1007/s11934-015-0488-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11934-015-0488-8

Keywords

Search

Navigation