Skip to main content
SpringerLink
Log in
Book cover

Management of Prostate Cancer pp 217–230Cite as

Combination of Androgen Deprivation Therapy and Radiation Therapy for Locally Advanced and Localized Prostate Cancer

  • Chapter
  • First Online:

  • 1298 Accesses

Abstract

High-risk prostate cancer requests external beam irradiation combined with androgen deprivation therapy (ADT) to potentiate irradiation, whatever its technique, and to destroy the infra-clinical disease located outside the planning treatment volume. Randomized phase III trials have paved the way for establishing the indications and the duration of androgen deprivation therapy. Image-guided intensity modulated radiotherapy is the gold standard. Long term androgen deprivation therapy (≥2 years) with luteinizing hormone-releasing hormone agonists combined with external irradiation should be recommended for high-risk prostate cancer. For intermediate-risk localized prostate cancer, patients may benefit from a combined approach with a short term ADT (4–6 month); for patients unsuitable for ADT, due to co-morbidities or unwilling to accept androgen deprivation therapy to preserve their sexual health, the recommended treatment is intensity modulated radiotherapy at a dose of 76–80 Gy or a combination of intensity modulated radiotherapy and brachytherapy. The patients need to be informed of the potential morbidity of ADT and a close cooperation is needed with general practitioners and specialists to prevent and mitigate side effects and maintain quality of life.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   119.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Asbell SO, Krall JM, Pilepich MV, et al. Elective pelvic irradiation in stage A2, B carcinoma of the prostate: analysis of RTOG 77–06. Int J Radiat Oncol Biol Phys. 1988;15:1307–16.

    Article  CAS  PubMed  Google Scholar 

  2. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bolla M, Gonzalez D, Warde P, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserilin. N Engl J Med. 1997;337:295–300.

    Article  CAS  PubMed  Google Scholar 

  4. Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002;360:103–6.

    Article  CAS  PubMed  Google Scholar 

  5. Bolla M, de Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009;360:2516–27.

    Article  CAS  PubMed  Google Scholar 

  6. Bolla M, Hannoun-Levi JM, Ferrero JM, et al. Concurrent and adjuvant docetaxel with three-dimensional conformal radiation therapy plus androgen deprivation for high-risk prostate cancer: preliminary results of a multicentre phase II trial. Radiother Oncol. 2010;97:312–7.

    Article  CAS  PubMed  Google Scholar 

  7. Bolla M, van Tienhoven G, Warde P, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomized study. Lancet Oncol. 2010;11:1066–73.

    Article  CAS  PubMed  Google Scholar 

  8. Bolla M, Maingon P, Carrie C, et al. Short term androgen suppression and radiation dose escalation for intermediate and high-rsk localized prostate cancer: results of EORTC trial 22991. J Clin Oncol. 2016;34(15):1748–56. http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2015.64.8055.

    Article  PubMed  Google Scholar 

  9. Briganti A, Karnes RJ, Da Pozzo LP, et al. Combination of adjuvant hormonal and radiation therapy significantly prolongs survival of patients with pT2-4 pN+ prostate cancer: results of a matched analysis. Eur Urol. 2011;59:832–40.

    Article  CAS  PubMed  Google Scholar 

  10. D’Amico AV, Denham JW, Crook J, et al. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol. 2007;25:2420–5.

    Article  PubMed  Google Scholar 

  11. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA. 2008;299:289–95.

    PubMed  Google Scholar 

  12. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Long-term follow-up of a randomized trial of radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. 2015;314:1291–3.

    Article  PubMed  Google Scholar 

  13. De Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastattic prostate cancer. N Engl J Med. 2011;364:1995–2005.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Denham JW, Steigler A, Lamb DS, et al. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol. 2005;6:841–50.

    Article  CAS  PubMed  Google Scholar 

  15. Denham JW, Steigler A, Lamb DS, et al. Short term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol. 2011;12(5):451–9.

    Article  CAS  PubMed  Google Scholar 

  16. Diamond TH, Higano CS, Smith MR, Guise TA, Singer FR. Osteoporosis in men with prostate carcinoma receiving androgen-deprivation therapy: recommendations for diagnosis and therapies. Cancer. 2004;100:892–9.

    Article  PubMed  Google Scholar 

  17. Dubray BM, Beckendorf V, Guerif S, et al. Does short-term androgen depletion add to high-dose radiotherapy (80 Gy) in localized intermediate-risk prostate cancer? Intermediate analysis of GETUG 14 randomized trial (EU-20503/NCT00104741). J Clin Oncol. 2011;29:(suppl; abstr 4521).

    Google Scholar 

  18. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality and duration of androgen deprivation for locally advanced prostate cancer: analysis of RTOG 92–02. Eur Urol. 2008;54:816–23.

    Article  CAS  PubMed  Google Scholar 

  19. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85–31. J Clin Oncol. 2009;27:92–9.

    Article  PubMed  Google Scholar 

  20. Fizazi K, Lesaunier F, Delva R, et al. Docetaxel-estramustine in high-risk localized prostate cancer: first results of the French Genitourinary Tumor Group phase III trial (GETUG12). J Clin Oncol. 2011;29:(suppl; abstr 4513).

    Google Scholar 

  21. Fizazi K, Lesaunier F, Delva R, et al. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomzed trial. Lancet Oncol. 2015;16:787–94.

    Article  CAS  PubMed  Google Scholar 

  22. Fossa SD, et al. Ten-and 15-year prostate cancer-specific mortality in patients with non metastatic locally advanced or aggressive intermediate prostate cancer, randomized to lifelong endocrine treatment alone or combined with radiotherapy; final results of the Scandinavian Prostate Cancer Group-7. Eur Urol. 2016;70(4):684–91. http://dx.doi.org/10.1016/j.euro.2016.03.021.

    Article  PubMed  Google Scholar 

  23. Goodwin JF, Schiewer MJ, Dean JL, et al. A hormone-DNA repair circuit governs the response to genotoxic insult. Cancer Discov. 2013;3:1254–71.

    Article  CAS  PubMed  Google Scholar 

  24. Granfors T, Modig H, Damber JE, Tomic R. Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study. J Urol. 1998;159:2030–4.

    Article  CAS  PubMed  Google Scholar 

  25. Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and localized treatment with curative intent. Update 2013. Eur Urol. 2014;65:124–37.

    Article  PubMed  Google Scholar 

  26. Hennequin C, Giocanti N, Favaudon V. S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells. Br J Cancer. 1995;71:1194–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Horwitz EM, Bae K, Hanks GE, et al. Ten-year follow-up of radiation therapy oncology group protocol 92–02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008;26:2497–504.

    Article  CAS  PubMed  Google Scholar 

  28. Huggins C, Stevens RE, Hodges CV. Studies on prostatic cancer. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg. 1941;43:209–43.

    Article  CAS  Google Scholar 

  29. ICECap Working Group. The development of intermediate clinical endpoints in cancer of the prostate (ICECaP). J Natl Cancer Inst. 2015;107:1–8.

    Google Scholar 

  30. James ND, Spears MR, Clarke NW, et al. Failure-free survival and radiotherapy in patients with newly diagnosed nonmetastatic prostate cancer. JAMA Oncol. 2015;2(3):348–57. doi:10.1001/jamaoncol.2015.4350 1–10.

    Article  Google Scholar 

  31. Jones CU, Hunt D, McGowan DG, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011;365:107–18.

    Article  CAS  PubMed  Google Scholar 

  32. Joon DL, Hasegawa M, Sikes C, et al. Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation. Int J Radiat Oncol Biol Phys. 1997;38:1071–7.

    Article  CAS  PubMed  Google Scholar 

  33. Kalbasi A. Dose escalated irradiation and overall survival in men with non metastatic prostate cancer. JAMA Oncol. 2015;1:897–906.

    Article  PubMed  Google Scholar 

  34. Kaminski JM, Hanlon AL, Joon DL, Meistrich M, Hachem P, Pollack A. Effect of sequencing of androgen deprivation and radiotherapy on prostate cancer growth. Int J Radiat Oncol Biol Phys. 2003;57:24–8.

    Article  CAS  PubMed  Google Scholar 

  35. 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 prosytate cancer. BJU Int. 2008;102:1531–8.

    Article  CAS  PubMed  Google Scholar 

  36. Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res. 2009;15:4792–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kumar P, Perrotti M, Weiss R, et al. Phase I trial of weekly docetaxel with concurrent three-dimensional conformal radiation therapy in the treatment of unfavorable localized adenocarcinoma of the prostate. J Clin Oncol. 2004;22:1909–15.

    Article  CAS  PubMed  Google Scholar 

  38. Lawton CA, Winter K, Byhardt R, et al. Androgen suppression plus radiation versus radiation alone for patients with D1/pathologic node-positive adenocarcinoma of the prostate : updated results based on a national prospective randomized trial, Radiation Therapy Oncology Group 85–31. Int J Radiat Oncol Biol Phys. 2005;23:800–7.

    Google Scholar 

  39. Lawton CA, DeSivio M, Roach 3rd M, et al. An update of the phase III trial comparing whole pelvis to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression.: update analysis of RTOG 94–13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys. 2007;69:646–55.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lawton CA, Winter K, Murray K, et al. Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85–31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2001;49:937–9.

    Article  CAS  PubMed  Google Scholar 

  41. Labrie F, Belanger A, Simard J, Labrie C, Dupont A. Combination therapy for prostate cancer. Endocrine and biologic basis of its choice as new standard first-line therapy. Cancer. 1993;71:1059–67.

    Article  CAS  PubMed  Google Scholar 

  42. Lalonde E, Ishkanian AS, Sykes J, et al. Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study. Lancet Oncol. 2014;15:1521–32.

    Article  PubMed  Google Scholar 

  43. Lin CC, Gray PJ, Jemal A, Efstathiou JA. Androgen deprivation with or withoiut radiation therapy for clinically node-positive prostate cancer. J Natl Cancer Inst. 2015;107:1–10.

    Google Scholar 

  44. Mason M. Final report of the Intergroup Randomized Study of Ciombined Androgen deprivationtherapy plus radiotherapy versus androgen deprivation therapy alone in locally advanced prostate cancer. J Clin Oncol. 2015;33:2143–9.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Prostate Cancer Trialists’ Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet. 2000;355:1491–8.

    Article  Google Scholar 

  46. Milosevic M, Chung P, Parker C, et al. Androgen withdrawal in patients reduces prostate cancer hypoxia: implications for disease progression and radition response. Cancer Res. 2007;67:6022–5.

    Article  CAS  PubMed  Google Scholar 

  47. Mottet N, Peneau M, Mazeron J-J, Molinie V, Richaud P. Addition of radiotherapy to long term androgen deprivation in locally advanced prostate cancer: an open randomised phase 3 trial. Eur Urol. 2012;62:213–9.

    Article  PubMed  Google Scholar 

  48. Mottet N, Bellmunt J, Briers E, et al. members of the EAU – ESTRO – SIOG Prostate Cancer Guidelines Panel. EAU – ESTRO – SIOG guidelines on prostate cancer. Edn. Presented at the EAU Annual Congress Munich 2016. EAU Guidelines Office, Arnhem; 2016. ISBN 978-90-79754-98-4. https://uroweb.org/guideline/prostate-cancer/.

  49. Nabid A, Carrier N, Martin AG, et al. High-risk prostate cancer treated with pelvic radiotherapy and 36 months versus 18 months of androgen blockade. Results of a phase III randomized study. J Clin Oncol. 2013;31:(suppl 6; abstr 3).

    Google Scholar 

  50. Nguyen PL, Alibhai SMH, Basaria S, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015;67:825–36.

    Article  CAS  PubMed  Google Scholar 

  51. Parmar H, Philipps RH, Lightman SL, Edwards L, Allen L, Schally AV. Randomised controlled study of orchidectomy vs long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma. Lancet. 1985;2:1201–5.

    Article  CAS  PubMed  Google Scholar 

  52. 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 

  53. Pilepich MV, Winter K, Lawton CA, et al. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma – long-term results of phase III RTOG 85–31. Int J Radiat Oncol Biol Phys. 2005;61:1285–90.

    Article  CAS  PubMed  Google Scholar 

  54. Pisansky TM, Hunt D, Gomella LG, et al. Duration of androgen suppression before radiotherapy for localized prostate cancer: Radiation Therapy Oncology Group randomized clinical trial 9910. J Clin Oncol. 2015;33:332–9.

    Article  PubMed  Google Scholar 

  55. Pommier P, Chabaud S, Lagrange JL, et al. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol. 2007;25:5366–73.

    Article  PubMed  Google Scholar 

  56. Potosky AL, Knopf K, Clegg LX, et al. Quality-of-life outcomes after primary androgen deprivation therapy: results from the Prostate Cancer Outcomes Study. J Clin Oncol. 2001;19:3750–7.

    CAS  PubMed  Google Scholar 

  57. 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.

    Article  CAS  PubMed  Google Scholar 

  58. Roach 3rd M, Bae K, Speight J, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 86–10. J Clin Oncol. 2008;26:585–91.

    Article  PubMed  Google Scholar 

  59. Sandler HM, et al. J Clin Oncol. 2015;33:(15S).

    Google Scholar 

  60. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in proste cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.

    Article  CAS  PubMed  Google Scholar 

  61. Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature. 1979;277:665–7.

    Article  CAS  PubMed  Google Scholar 

  62. Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2007;352:154–64.

    Article  Google Scholar 

  63. Smith MR, Bae K, Efstathiou JA, et al. Diabetes and mortality in men with locally advanced prostate cancer. J Clin Oncol. 2008;26:4333–9.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Smith MR, Lee H, McGovern F, et al. Metabolic changes during gonadotrophin-releasing hormone agonist therapy for prostate cancer. Differences from the classic metabolic syndrome. Cancer. 2008;112:2188–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Smith MR, Egerdie B, Hernandez Toriz N, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361:745–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. 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 

  67. Tran E, Paquette M, PicklesT et al. Population-based validation of a policy change to use long-term androgen deprivation therapy for cT3-4 prostate cancer: impact of the EORTC22863 and RTOG 85-31 and 92-02 trials. Radioth Oncol, 2013;107(3):366–71.

    Google Scholar 

  68. Tyrell CJ, Payne H, See WA, et al. Bicalutamide (‘Casodex’) 150 mg as adjuvant to radiotherapy in patients with localised or locally advanced prostate cancer:results from the randomised early prostate cancer programme. Radiat Oncol. 2005;76:4–10.

    Article  Google Scholar 

  69. Valicenti RK, Kwounghwa B, Michalski J, et al. Does hormone therapy reduce disease recurrence in prostate cancer patienst receiving dose-escalated radiation therapy? An analysis of Radiation Therapy Oncology Group 94–06. Int J Radiat Oncol Biol Phys. 2011;79:1323–2912.

    Article  CAS  PubMed  Google Scholar 

  70. Viani GA, Stefano EJ, Afonso SL. Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys. 2009;74(5):1405–18.

    Article  PubMed  Google Scholar 

  71. Widmark A, Klepp O, Solberg A, et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009;373:301–30.

    Article  CAS  PubMed  Google Scholar 

  72. Zietman AL, Prince EA, Nakfoor BM, Park JJ. Androgen deprivation and radiation therapy: sequencing studies using the Shionogi in vivo tumor system. Int J Radiat Oncol Biol Phys. 1997;38:1067–70.

    Article  CAS  PubMed  Google Scholar 

  73. Zapatero A, Valcarcel F, Calvo FA, et al. Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study. J Clin Oncol. 2005;23:6561–8.

    Article  PubMed  Google Scholar 

  74. Zapatero A, Guerrero A, Maldonado X, et al. High-dose radiotherapy with short-term or long term androgen deprivation in localized prostate cancer (DART01/05 GICOR): a randomized, controlled, phase 3 trial. Lancet Oncol. 2015;16:320–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinique Universitaire de Cancérologie-Radiothérapie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble Alpes Université, BP 217 38043, Grenoble cedex 9, France

    Michel Bolla, Camille Verry & Carole Iriart

Authors
  1. Michel Bolla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Camille Verry
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carole Iriart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michel Bolla .

Editor information

Editors and Affiliations

  1. Department of Radiation Oncology, Hôpital Albert Michallon, Grenoble, France

    Michel Bolla

  2. Department of Urology, University Hospitals Leuven, Leuven, Belgium

    Hendrik van Poppel

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bolla, M., Verry, C., Iriart, C. (2017). Combination of Androgen Deprivation Therapy and Radiation Therapy for Locally Advanced and Localized Prostate Cancer. In: Bolla, M., van Poppel, H. (eds) Management of Prostate Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-42769-0_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-42769-0_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-42768-3

  • Online ISBN: 978-3-319-42769-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation