Skip to main content
Log in

Timing of androgen deprivation monotherapy and combined treatments in castration-sensitive and castration-resistant prostate cancer: a narrative review

  • Topic Paper
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

Standard androgen deprivation therapy (ADT) can be initiated early at the time of diagnosis in asymptomatic castration-sensitive advanced prostate cancer. This definition has recently been expanded to also include an early combined treatment with standard ADT and new antihormonal drugs. We aimed to present the best available evidence for the timing of initiation of ADT monotherapy and combined treatments in castration-sensitive/-resistant prostate cancer.

Methods

For this narrative review, we searched Cochrane reviews in the Cochrane Library, systematic reviews and randomized controlled trials in MEDLINE, phase III and ongoing trials in ClinicalTrials.gov and screened the reference lists to extract articles of interest. One author screened the references which were finally included after assessing their relevance through discussion with other experts in the field.

Results

The identified references were grouped by medication (standard ADT, androgen biosynthesis inhibitor, androgen receptor antagonists or combined therapies) and tumor stage (castration sensitive or resistant). The evidence was narratively summarized and discussed in the context of the current therapeutic landscape.

Conclusions

Early standard ADT can reduce symptoms of disease progression and may extend progression-free and overall survival. The patient should be well informed about the higher rates of treatment-related side effects. Deferring standard ADT might be indicated only for well-informed or unfit patients. Early standard ADT is increasingly combined with new antihormonal drugs in castration-sensitive metastatic prostate cancer to gain additional survival and quality of life benefits. Combined treatment at the time of development of castration-resistant disease is well established.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Antonarakis ES, Eisenberger MA (2009) Is abiraterone acetate well tolerated and effective in the treatment of castration-resistant prostate cancer? Nat Clin Pract Oncol 6(1):12–13

    Article  CAS  PubMed  Google Scholar 

  2. Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V et al (2009) Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324(5928):787–790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shore ND (2017) Darolutamide (ODM-201) for the treatment of prostate cancer. Expert Opin Pharmacother 18(9):945–952

    Article  CAS  PubMed  Google Scholar 

  4. Al-Salama ZT (2018) Apalutamide: first global approval. Drugs 78(6):699–705

    Article  CAS  PubMed  Google Scholar 

  5. Hammerer PG, Wirth MP, Group EED-NL-s (2018) Health-related quality of life in 536 long-term prostate cancer survivors after treatment with leuprorelin acetate: a combined retrospective and prospective analysis. Urol Int 100(1):72–78

    Article  CAS  PubMed  Google Scholar 

  6. Kunath F, Keck B, Rucker G, Motschall E, Wullich B, Antes G et al (2013) Early versus deferred androgen suppression therapy for patients with lymph node-positive prostate cancer after local therapy with curative intent: a systematic review. BMC Cancer 13:131

    Article  PubMed  PubMed Central  Google Scholar 

  7. Nair B, Wilt T, MacDonald R, Rutks I (2002) Early versus deferred androgen suppression in the treatment of advanced prostatic cancer. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD003506

    Article  PubMed  Google Scholar 

  8. John Wiley & Sons Inc. (2018) Cochrane Library. https://www.cochranelibrary.com/. Acessed date 30 Sep 2018

  9. Rydzewska LHM, Burdett S, Vale CL, Clarke NW, Fizazi K, Kheoh T et al (2017) Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis. Eur J Cancer 84:88–101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Vale CL, Fisher DJ, White IR, Carpenter JR, Burdett S, Clarke NW et al (2018) What is the optimal systemic treatment of men with metastatic, hormone-naive prostate cancer? A STOPCAP systematic review and network meta-analysis. Ann Oncol 29(5):1249–1257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tan PS, Aguiar P Jr, Haaland B, Lopes G (2018) Addition of abiraterone, docetaxel, bisphosphonate, celecoxib or combinations to androgen-deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC): a network meta-analysis. Prostate Cancer Prost Dis 21:516–523

    Article  CAS  Google Scholar 

  12. Feyerabend S, Saad F, Li T, Ito T, Diels J, Van Sanden S et al (2018) Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: a network meta-analysis. Eur J Cancer 103:78–87

    Article  CAS  PubMed  Google Scholar 

  13. Kassem L, Shohdy KS, Abdel-Rahman O (2018) Abiraterone acetate/androgen deprivation therapy combination versus docetaxel/androgen deprivation therapy combination in advanced hormone-sensitive prostate cancer: a network meta-analysis on safety and efficacy. Curr Med Res Opin 34(5):903–910

    Article  CAS  PubMed  Google Scholar 

  14. McNamara M, Sweeney C, Antonarakis ES, Armstrong AJ (2018) The evolving landscape of metastatic hormone-sensitive prostate cancer: a critical review of the evidence for adding docetaxel or abiraterone to androgen deprivation. Prostate Cancer and prostatic Dis 21(3):306–318

    Article  CAS  Google Scholar 

  15. Xu L, Pachynski RK (2018) Contemporary management of the newly diagnosed prostate cancer patient with metastatic disease at presentation. Curr Urol Rep 19(10):79

    Article  PubMed  Google Scholar 

  16. U.S. National Library of Medicine. ClinicalTrials.gov. (2018) https://www.clinicaltrials.gov/(last. Assessed date 30 Sep 2018

  17. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY et al (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 377(4):352–360

    Article  CAS  PubMed  Google Scholar 

  18. James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP et al (2017) Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 377(4):338–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Schmitt B, Bennett C, Seidenfeld J, Samson D, Wilt T (2000) Maximal androgen blockade for advanced prostate cancer. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD001526

    Article  PubMed  Google Scholar 

  20. Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ et al (2012) Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 13(10):983–992

    Article  CAS  PubMed  Google Scholar 

  21. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21):1995–2005

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368(2):138–148

    Article  CAS  PubMed  Google Scholar 

  23. Poorthuis MHF, Vernooij RWM, van Moorselaar RJA, de Reijke TM (2017) First-line non-cytotoxic therapy in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of 10 randomised clinical trials. BJU Int 119(6):831–845

    Article  CAS  PubMed  Google Scholar 

  24. Saeterdal I, Desser A, Pike E, Hamidi V, Harboe I, Odgaard-Jensen J et al (2016) Health technology assessment of four drugs for patients with metastatic castration resistant prostate cancer. NIPH Systematic Reviews. Oslo, Norway

    Google Scholar 

  25. Moreira RB, Debiasi M, Francini E, Nuzzo PV, Velasco G, Maluf FC et al (2017) Differential side effects profile in patients with mCRPC treated with abiraterone or enzalutamide: a meta-analysis of randomized controlled trials. Oncotarget 8(48):84572–84578

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wang Y, Zhang H, Shen W, He P, Zhou Z (2018) Effectiveness and tolerability of targeted drugs for the treatment of metastatic castration-resistant prostate cancer: a network meta-analysis of randomized controlled trials. J Cancer Res Clin Oncol 144(9):1751–1768

    Article  CAS  PubMed  Google Scholar 

  27. Zhao Y, Huang H, Chen C, Liu H, Su F, Bi J et al (2018) Efficacy and safety of different interventions in castration resistant prostate cancer progressing after docetaxel-based chemotherapy: Bayesian network analysis of randomized controlled trials. J Cancer 9(4):690–701

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Marchioni M, Sountoulides P, Bada M, Rapisarda S, De Nunzio C, Tamburro FR et al (2018) Abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of ‘real-life’ studies. Ther Adv Urol 10(10):305–315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tassinari D, Cherubini C, Roudnas B, Tamburini E, Drudi F, Bianchi E et al (2018) Treatment of metastatic, castration-resistant, docetaxel-resistant prostate cancer: a systematic review of literature with a network meta-analysis of randomized clinical trials. Rev Recent Clin Trials 13(3):226–237

    Article  CAS  PubMed  Google Scholar 

  30. Shore ND, Chowdhury S, Villers A, Klotz L, Siemens DR, Phung D et al (2016) Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol 17(2):153–163

    Article  CAS  PubMed  Google Scholar 

  31. Klotz L, Drachenberg D, Singal R, Aprikian A, Fradet Y, Kebabdjian M et al (2014) An open-label, phase 2 trial of bicalutamide dose escalation from 50 mg to 150 mg in men with CAB and castration resistance. A Canadian Urology Research Consortium Study. Prostate Cancer Prost Dis 17(4):320–324

    Article  CAS  Google Scholar 

  32. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367(13):1187–1197

    Article  CAS  PubMed  Google Scholar 

  33. Fizazi K, Scher HI, Miller K, Basch E, Sternberg CN, Cella D et al (2014) Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Lancet Oncol 15(10):1147–1156

    Article  CAS  PubMed  Google Scholar 

  34. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371(5):424–433

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Loriot Y, Miller K, Sternberg CN, Fizazi K, De Bono JS, Chowdhury S et al (2015) Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncol 16(5):509–521

    Article  CAS  PubMed  Google Scholar 

  36. Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U et al (2018) Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med 378(26):2465–2474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zheng H, Chen J, Qiu W, Lin S, Chen Y, Liang G, et al. (2017) Safety and efficacy of first-line treatments for chemotherapy-naive metastatic castration-resistant prostate cancer: a systematic review and indirect comparison. BioMed Res Int ID3941217:10

  38. Poorthuis MHF, Vernooij RWM, van Moorselaar RJA, de Reijke TM (2017) Second-line therapy in patients with metastatic castration-resistant prostate cancer with progression after or under docetaxel: a systematic review of nine randomized controlled trials. Semin Oncol 44(5):358–371

    Article  CAS  PubMed  Google Scholar 

  39. Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN et al (2018) Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 378(15):1408–1418

    Article  CAS  PubMed  Google Scholar 

  40. Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S et al (2018) Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol 19:1404–1414

    Article  CAS  PubMed  Google Scholar 

  41. Massard C, Penttinen HM, Vjaters E, Bono P, Lietuvietis V, Tammela TL et al (2016) Pharmacokinetics, antitumor activity, and safety of ODM-201 in patients with chemotherapy-naive metastatic castration-resistant prostate cancer: an open-label phase 1 study. Eur Urol 69(5):834–840

    Article  CAS  PubMed  Google Scholar 

  42. Fizazi K, Albiges L, Loriot Y, Massard C (2015) ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer. Expert Rev Anticancer Ther 15(9):1007–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fizazi K, Smith MR, Tombal B (2018) Clinical development of darolutamide: a novel androgen receptor antagonist for the treatment of prostate cancer. Clin Genitourin Cancer 16(5):332–340. https://doi.org/10.1016/j.clgc.2018.07.017

    Article  PubMed  Google Scholar 

  44. Mottet N, van den Bergh RCN, Briers E, Bourke L, Cornford P, De Santis M, et al. (2018) EAU—ESTRO—ESUR—SIOG Guidelines on prostate cancer. European Association of Urology. http://uroweb.org/guideline/prostate-cancer/ Assessed 30 Sep 2018

  45. Kunath F, Grobe HR, Rücker G, Motschall E, Antes G, Dahm P, Wullich B, Meerpohl JJ (2014) Non-steroidal antiandrogen monotherapy compared with luteinising hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD009266.pub2

    Article  PubMed  Google Scholar 

  46. Cramp F, Byron-Daniel J (2012) Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev 11:CD006145. https://doi.org/10.1002/14651858.CD006145.pub3

    Article  PubMed  Google Scholar 

  47. Tucci M, Leone G, Buttigliero C, Zichi C, Di Stefano RF, Pignataro D et al (2018) Hormonal treatment and quality of life of prostate cancer patients: new evidence. Minerva Urol Nefrol 70(2):144–151

    PubMed  Google Scholar 

  48. Ost P, Bossi A, Decaestecker K, De Meerleer G, Giannarini G, Karnes RJ et al (2015) Metastasis-directed therapy of regional and distant recurrences after curative treatment of prostate cancer: a systematic review of the literature. Eur Urol 67(5):852–863

    Article  PubMed  Google Scholar 

  49. Kunath F, Borgmann H, Blumle A, Keck B, Wullich B, Schmucker C et al (2015) Gonadotropin-releasing hormone antagonists versus standard androgen suppression therapy for advanced prostate cancer. a systematic review with meta-analysis. BMJ Open 5(11):e008217

    Article  PubMed  PubMed Central  Google Scholar 

  50. Gravis G, Boher JM, Joly F, Soulie M, Albiges L, Priou F et al (2016) Androgen deprivation therapy (ADT) plus docetaxel versus adt alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol 70(2):256–262

    Article  CAS  PubMed  Google Scholar 

  51. Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B et al (2013) 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 14(2):149–158

    Article  CAS  PubMed  Google Scholar 

  52. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M et al (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373(8):737–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR et al (2016) 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 387(10024):1163–1177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM et al (2018) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol 36(11):1080–1087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

FK project development, data collection or management, data analysis, and manuscript writing/editing. PJG data analysis and manuscript writing/editing. BW data analysis and manuscript writing/editing. DS data analysis and manuscript writing/editing. AK data analysis and manuscript writing/editing.

Corresponding author

Correspondence to F. Kunath.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest concerning the topic of this publication. The authors confirm that the project development and writing of manuscript was not funded.

Research involving human participants and/or animals

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

Informed consent

For this type of study, formal consent is not required. All the authors have read and approved the manuscript, and it has not been submitted elsewhere. All the authors had full access to all study data and take full responsibility for the integrity of the data and the accuracy of the data analysis.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kunath, F., Goebell, P.J., Wullich, B. et al. Timing of androgen deprivation monotherapy and combined treatments in castration-sensitive and castration-resistant prostate cancer: a narrative review. World J Urol 38, 601–611 (2020). https://doi.org/10.1007/s00345-019-02704-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-019-02704-y

Keywords

Navigation