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Corticosteroids in the Management of Prostate Cancer: A Critical Review

  • Genitourinary Cancers (W Oh and M Galsky, Section Editors)
  • Published:
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Opinion statement

Corticosteroids have been used in the management of prostate cancer for over 30 years. Although daily oral corticosteroids have frequently used in conjunction with chemotherapy for metastatic castration-resistant prostate cancer, their independent impact on survival is unclear. However, corticosteroids confer palliative benefits and are associated with objective responses and circulating tumor cell (CTC) and PSA declines in a small minority of patients, although toxicities such as osteoporosis and immunosuppression complicate long-term use. Following the demonstration of a palliative benefit for mitoxantrone combined with corticosteroids compared with corticosteroids alone, subsequent trials that demonstrated a benefit for first-line docetaxel over mitoxantrone, and second-line cabazitaxel over mitoxantrone, administered concurrent daily oral corticosteroids with all of these agents to maintain uniformity. Conversely, improved outcomes were demonstrated with docetaxel without corticosteroids for metastatic castration-sensitive prostate cancer. Daily oral corticosteroids are routinely combined with abiraterone to mitigate symptoms of mineralocorticoid excess. In contrast daily corticosteroids are not essential when administering enzalutamide or radium-223, and there is a concern of deleterious immune effects concurrently with sipuleucel-T. Given emerging evidence for promotion of resistance mechanisms, routine administration of daily oral corticosteroids in settings other than abiraterone administration and palliation of symptoms is probably not required.

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References and Recommended Reading

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  1. 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;351:1502–12.

    Article  CAS  PubMed  Google Scholar 

  2. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.

    Article  CAS  PubMed  Google Scholar 

  3. de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147–54.

    Article  PubMed  Google Scholar 

  4. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97. This paper reports the results of the pivotal AFFIRM placebo-controlled phase III trial, which demonstrated extension of survival for enzalutamide vs placebo for post-docetaxel men with metastatic castration-resistant prostate cancer. Corticosteroids were not required, but were allowed in both arms.

    Article  CAS  PubMed  Google Scholar 

  5. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    Article  CAS  PubMed  Google Scholar 

  6. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. N Engl J Med. 2014;371:424–33. This paper reports the results of the pivotal PREVAIL placebo-controlled phase III trial, which demonstrated extension of survival for enzalutamide vs placebo for docetaxel-naïve men with metastatic castration-resistant prostate cancer. Corticosteroids were not required, but were allowed in both arms.

  7. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48. This paper reports the results of the pivotal COU-AA-302 placebo-controlled phase III trial comparing prednisone alone vs prednisone plus abiraterone acetate for docetaxel-naïve men with metastatic castration-resistant prostate cancer. Although prednisone alone showed modest activity, the combination of prednisone and abiraterone acetate extended overall survival.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005. This paper reports the results of the pivotal COU-AA-301 placebo-controlled phase III trial comparing prednisone alone vs prednisone plus abiraterone acetate for post-docetaxel men with metastatic castration-resistant prostate cancer. Although prednisone alone showed modest activity, the combination of prednisone and abiraterone acetate extended overall survival.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Nishimura K, Nonomura N, Satoh E, et al. Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer. J Natl Cancer Inst. 2001;93:1739–46.

    Article  CAS  PubMed  Google Scholar 

  10. Tannock I, Gospodarowicz M, Meakin W, Panzarella T, Stewart L, Rider W. Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol. 1989;7:590–7.

    CAS  PubMed  Google Scholar 

  11. Yano A, Fujii Y, Iwai A, Kageyama Y, Kihara K. Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells. Clin Cancer Res. 2006;12:3003–9.

    Article  CAS  PubMed  Google Scholar 

  12. Yano A, Fujii Y, Iwai A, Kawakami S, Kageyama Y, Kihara K. Glucocorticoids suppress tumor lymphangiogenesis of prostate cancer cells. Clin Cancer Res. 2006;12:6012–7.

    Article  CAS  PubMed  Google Scholar 

  13. Venkitaraman R, Thomas K, Huddart RA, Horwich A, Dearnaley DP, Parker CC. Efficacy of low-dose dexamethasone in castration-refractory prostate cancer. BJU Int. 2008;101:440–3.

    CAS  PubMed  Google Scholar 

  14. Storlie JA, Buckner JC, Wiseman GA, Burch PA, Hartmann LC, Richardson RL. Prostate specific antigen levels and clinical response to low dose dexamethasone for hormone-refractory metastatic prostate carcinoma. Cancer. 1995;76:96–100.

    Article  CAS  PubMed  Google Scholar 

  15. Nishimura K, Nonomura N, Yasunaga Y, et al. Low doses of oral dexamethasone for hormone-refractory prostate carcinoma. Cancer. 2000;89:2570–6.

    Article  CAS  PubMed  Google Scholar 

  16. Saika T, Kusaka N, Tsushima T, et al. Treatment of androgen-independent prostate cancer with dexamethasone: a prospective study in stage D2 patients. Int J Urol. 2001;8:290–4.

    Article  CAS  PubMed  Google Scholar 

  17. Sartor O, Weinberger M, Moore A, Li A, Figg WD. Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer. Urology. 1998;52:252–6.

    Article  CAS  PubMed  Google Scholar 

  18. Kantoff PW, Halabi S, Conaway M, et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol. 1999;17:2506–13.

    CAS  PubMed  Google Scholar 

  19. Tannock IF, Osoba D, Stockler MR, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996;14:1756–64.

    CAS  PubMed  Google Scholar 

  20. Beer TM, Pierce WC, Lowe BA, Henner WD. Phase II study of weekly docetaxel in symptomatic androgen-independent prostate cancer. Ann Oncol. 2001;12:1273–9.

    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;351:1513–20.

    Article  CAS  PubMed  Google Scholar 

  22. Health NIH. NIH-funded study shows increased survival in men with metastatic prostate cancer who receive chemotherapy when starting hormone therapy. Available at: http://www.nih.gov/news/health/dec2013/nci-05.htm. Accessed 24 Feb 2014.

  23. Sweeney CJ CY-H, 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. J Clin Oncol. 2014;32(Suppl):5s [Abstr act LBA2].

    Google Scholar 

  24. 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;14:149–58.

    Article  CAS  PubMed  Google Scholar 

  25. Scher HI HG, Molina GA, et al. Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): planned final analysis (FA) of COU-AA-301, a randomized double-blind, placebo-controlled phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel. J Clin Oncol. 2011;29 (Suppl). [Abstract LBA4517^].

  26. De Wit R, Fizazi K, Jinga V, et al. Phase 3, randomized, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients (pts) with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) (ELM-PC 4 trial). J Clin Oncol. 2014;32(Suppl):5s. [Abstract 5008].

  27. Fizazi K, Jones R, Oudard S, et al. Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5. J Clin Oncol. 2015. doi:10.1200/JCO.2014.56.5119.

  28. Dreicer R Jones R, Oudard S, et al. Results from a phase 3, randomized, double-blind, multicenter, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy (ELM-PC 5 trial). J Clin Oncol. 2014;32(Suppl 4). [Abstract 7^].

  29. Attard G, Reid AH, de Bono JS. Abiraterone acetate is well tolerated without concomitant use of corticosteroids. J Clin Oncol. 2010;28:e560–1; author reply e2.

  30. Small EJ, Lance RS, Redfern CH, et al. A randomized phase II trial of sipuleucel-T with concurrent or sequential abiraterone acetate (AA) plus prednisone (P) in metastatic castrate-resistant prostate cancer. J Clin Oncol. 2013;31(Suppl). [Abstr 5047^].

  31. Kwon ED, Drake CG, Scher HI, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15:700–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Morgan CJ, Oh WK, Naik G, Galsky MD, Sonpavde G. Impact of prednisone on toxicities and survival in metastatic castration-resistant prostate cancer: a systematic review and meta-analysis of randomized clinical trials. Crit Rev Oncol Hematol. 2014;90:253–61.

    Article  PubMed  Google Scholar 

  33. Scher HI, Jia X, Chi K, et al. Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. J Clin Oncol. 2011;29:2191–8.

  34. Fossa SD, Slee PH, Brausi M, et al. Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group. J Clin Oncol. 2001;19:62–71.

    CAS  PubMed  Google Scholar 

  35. Higano CS SF, Curti BD, et al. A phase III trial of GVAX immunotherapy for prostate cancer versus docetaxel plus prednisone in asymptomatic, castration-resistant prostate cancer (CRPC). Genitourinary Cancers Symposium; February 26–28, 2009. Orlando, FL, USA; 2009. [Abstract LBA150].

  36. Small E, Demkow, T, Gerritsen, WR, et al. A phase III trial of GVAX immunotherapy for prostate cancer in combination with docetaxel versus docetaxel plus prednisone in symptomatic, castration-resistant prostate cancer (CRPC). Proceedings Genitourinary Cancer Symposium February 2009, Orlando, FL. 2009. [Abstract 7].

  37. Scher HI, Fizazi K, Saad F, et al. Association of baseline corticosteroid with outcomes in a multivariate analysis of the phase 3 Affirm study of enzalutamide (ENZA), an androgen receptor signaling inhibitor (ARSI). European Society for Medical Oncology meeting, Vienna, Austria; September 28-October 2, 2012. This retrospective analysis of patients receiving enzalutamide in the AFFIRM trial identified that men receiving corticosteroids at baseline had a significantly worse survival than those who did not.

  38. Arora VK, Schenkein E, Murali R, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 2013;155:1309–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Montgomery B, Kheoh T, Molina A, et al. Impact of baseline corticosteroids on survival and steroid androgens in metastatic castration-resistant prostate cancer: exploratory analysis from COU-AA-301. Eur Urol. 2014. doi:10.1016/j.eururo.2014.06.042. This retrospective analysis of patients receiving abiraterone acetate in the COU-AA-301 trial identified that corticosteroids at baseline did not confer an independent prognostic impact on survival.

  40. Ryan CJ, Molina A, Li J, et al. Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. J Clin Oncol. 2013;31:2791–8.

    Article  CAS  PubMed  Google Scholar 

  41. Taplin ME, Bubley GJ, Shuster TD, et al. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med. 1995;332:1393–8.

    Article  CAS  PubMed  Google Scholar 

  42. Taplin ME, Rajeshkumar B, Halabi S, et al. Androgen receptor mutations in androgen-independent prostate cancer: Cancer and Leukemia Group B Study 9663. J Clin Oncol. 2003;21:2673–8.

    Article  CAS  PubMed  Google Scholar 

  43. Chang CY, Walther PJ, McDonnell DP. Glucocorticoids manifest androgenic activity in a cell line derived from a metastatic prostate cancer. Cancer Res. 2001;61:8712–7.

    CAS  PubMed  Google Scholar 

  44. Richards J, Lim AC, Hay CW, et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res. 2012;72:2176–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Sahu B, Laakso M, Pihlajamaa P, et al. FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells. Cancer Res. 2013;73:1570–80.

    Article  CAS  PubMed  Google Scholar 

  46. Sharifi N. Steroid receptors aplenty in prostate cancer. N Engl J Med. 2014;370:970–1.

    Article  CAS  PubMed  Google Scholar 

  47. Dorff TB, Crawford ED. Management and challenges of corticosteroid therapy in men with metastatic castrate-resistant prostate cancer. Ann Oncol. 2013;24:31–8.

    Article  CAS  PubMed  Google Scholar 

  48. Oehling AG, Akdis CA, Schapowal A, Blaser K, Schmitz M, Simon HU. Suppression of the immune system by oral glucocorticoid therapy in bronchial asthma. Allergy. 1997;52:144–54.

    Article  CAS  PubMed  Google Scholar 

  49. 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;306:2359–66.

    Article  CAS  PubMed  Google Scholar 

  50. Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006;24:4448–56.

    Article  CAS  PubMed  Google Scholar 

  51. Saigal CS, Gore JL, Krupski TL, et al. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer. 2007;110:1493–500.

    Article  CAS  PubMed  Google Scholar 

  52. 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;377:813–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Alves C, Robazzi TC, Mendonca M. Withdrawal from glucocorticosteroid therapy: clinical practice recommendations. J Pediatr. 2008;84:192–202.

    Article  Google Scholar 

  54. Basch E, Autio K, Ryan CJ, et al. Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial. Lancet Oncol. 2013;14:1193–9.

    Article  CAS  PubMed  Google Scholar 

  55. Logothetis CJ, Basch E, Molina A, et al. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012;13:1210–7.

    Article  CAS  PubMed  Google Scholar 

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Conflict of Interest

Chuma Ndibe and Christopher G. Wang declare that they have no conflict of interest. Guru Sonpavde: advisory board and research support from Sanofi Aventis, Advisory board for Bayer.

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

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Authors and Affiliations

  1. Department of Medicine, Section of Hematology-Oncology, University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL, USA

    Chukwuma Ndibe MD, Christopher G. Wang MD & Guru Sonpavde MD

  2. Urologic Medical Oncology, University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL, USA

    Guru Sonpavde MD

  3. UAB School of Medicine, 1720 2nd Avenue South, NP2540B, Birmingham, AL, 35294-3300, USA

    Guru Sonpavde MD

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  1. Chukwuma Ndibe MD
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Correspondence to Guru Sonpavde MD.

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This article is part of the Topical Collection on Genitourinary Cancers

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Ndibe, C., Wang, C.G. & Sonpavde, G. Corticosteroids in the Management of Prostate Cancer: A Critical Review. Curr. Treat. Options in Oncol. 16, 6 (2015). https://doi.org/10.1007/s11864-014-0320-6

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