Early versus late hormonal therapy for prostate cancer

Abstract

Hormonal therapy remains the critical therapeutic option for men with advanced prostate cancer. However, considerable uncertainty remains regarding the appropriate choice/timing and actual benefits of hormonal therapy in various situations. This article reviews the relevant studies of immediate versus deferred hormonal therapy in patients with prostate cancer. The evidence from the data supports that early treatment is beneficial to many patients. Significant survival benefit of early hormonal therapy has been observed among patients with asymptomatic metastatic disease, node-positive but clinically localized disease after radical prostatectomy and lymphadenectomy, and advanced local/regional disease during and after radiotherapy.

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References and Recommended Reading

  1. 1.

    Byar DP: The Veterans Administration Cooperative Urological Research Group’s studies of cancer of the prostate. Cancer 1973, 32:1126–1130.

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Isaacs JT: The timing of androgen ablation therapy and/or chemotherapy in the treatment of prostatic cancer. Prostate 1984, 5:1–17.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Schally AV, Redding TW: Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model. Proc Nalt Acad Sci U S A 1985, 82:2498–2502.

    Article  CAS  Google Scholar 

  4. 4.

    Gingrich JR, Barrios RJ, Kattan MW, et al.: Androgen-independent prostate cancer progression in the TRAMP model. Cancer Res 1997, 57:4687–4691.

    PubMed  CAS  Google Scholar 

  5. 5.

    Eng MH, Charles LG, Ross BD, et al.: Early castration reduces prostatic carcinogenesis in transgenic mice. Urology 1999, 54:1112–1119.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Raghow S, Kuliyev E, Steakley M, et al.: Efficacious chemoprevention of primary prostate cancer by flutamide in an autochthonous transgenic model. Cancer Res 2000, 60:4093–4097.

    PubMed  CAS  Google Scholar 

  7. 7.

    Isaacs JT, Coffey DS: Adaptation versus selection as the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the Dunning R-3327-H adenocarinoma. Cancer Res 1981, 41:5070–5075.

    PubMed  CAS  Google Scholar 

  8. 8.

    Craft N, Chhor C, Tran C, et al.: Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process. Cancer Res 1999, 59:5030–5036.

    PubMed  CAS  Google Scholar 

  9. 9.

    Nonomura N, Nakamura N, Uchida N, et al.: Growth-stimulatory effect of androgen-induced autocrine growth factor(s) secreted from Shionogi carcinoma 115 cells on androgen-unresponsive cancer cells in a paracrine mechanism. Cancer Res 1988, 48:4904–4908.

    PubMed  CAS  Google Scholar 

  10. 10.

    Joseph IBJK, Nelson JB, Denmeade SR, Isaacs JT: Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue. Clin Cancer Res 1997, 3:2507–2511.

    PubMed  CAS  Google Scholar 

  11. 11.

    Zietman AL, Nakfoor BM, Prince EA, Gerweck LE: The effect of androgen deprivation and radiation therapy on an androgensensitive murine tumor: an in vitro and in vivo study. Cancer J Sci Am 1997, 3:31–36.

    PubMed  CAS  Google Scholar 

  12. 12.

    Joon DL, Hasegawa M, Sikes C, et al.: Supra-additive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation. Int J Radiat Oncol Biol Phys 1997, 38:1071–1077.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Pollack A, Salem N, Ashoori F, et al.: Lack of prostate cancer radiosensitization by androgen deprivation. Int J Radiat Oncol Biol Phys 2001, 51:1002–1007.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Hara I, Miyake H, Yamada Y, et al.: Neoadjuvant androgen withdrawal prior to external radiotherapy for locally advanced adenocarcinoma of the prostate. Int J Urol 2002, 9:322–328.

    PubMed  Article  Google Scholar 

  15. 15.

    Granfors T, Tomic R, Bergh A, et al.: After radiation testosterone stimulation is unable to increase growth in the dunning R3327-PAP prostate tumor. Urol Res 1999, 27:357–361.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Kaminski JM, Hanlon A, Joon DL, et al.: The effect of sequencing of androgen ablation and radiation on prostate cancer growth [Abstract]. Int J Radiat Oncol Biol Phys 2002, 54(suppl):190–191.

    Article  Google Scholar 

  17. 17.

    Gleave ME, Sato N, Goldenberg SL, et al.: Neoadjuvant androgen withdrawal therapy decreases local recurrence rates following tumor excision in the Shionogi tumor model. J Urol 1997, 157:1727–1730.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Byar DP, Corle DK: Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group studies. NCI Monogr 1988, 7:165–170.

    PubMed  Google Scholar 

  19. 19.

    The Medical Research Council Prostate Cancer Working Party Investigators Group: Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council trial. Br J Urol 1997, 79:235–246.

    Google Scholar 

  20. 20.

    Newling DW: Early versus late androgen deprivation therapy in metastatic disease. Urology 2001, 58(suppl 2A):50–55.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Kirk D: Immediate vs. deferred hormone treatment for prostate cancer: How safe is androgen deprivation [Abstract]? BJU Int 2000, 86(suppl 3):220.

    Google Scholar 

  22. 22.

    van den Ouden D, Tribukait B, Blom JHM, et al.: Deoxyribonucleic acid ploidy of core biopsies and metastatic lymph nodes of prostate cancer patients: impact on time to progression. J Urol 1993, 150:400–406.

    PubMed  Google Scholar 

  23. 23.

    Schröder FH, Kurth KH, Fossa SD, et al.: Early versus delayed endocrine treatment in pN1-3 M0 prostate cancer without local treatment of the primary tumor: results of EORTC 30846. A Phase III study [abstract]. J Urol 2003, 169(suppl 4):398.

    Google Scholar 

  24. 24.

    Studer UE, Hauri D, Dietrich D: Immediate vs deferred hormonal therapy for prostate cancer patients not suitable for curative local treatment [Abstract]. J Urol 2002, 167(suppl 4):303.

    Google Scholar 

  25. 25.

    Zagars GK, Johnson DE, von Eschenbach AC, Hussey DH: Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: long-term results of a prospective study. Int J Radiat Oncol Biol Phys 1988, 14:1085–1091.

    PubMed  CAS  Google Scholar 

  26. 26.

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

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Neymark N, Adriaenssen I, Gorlia T, et al.: Cost-effectiveness of the addition of early hormonal therapy in locally advanced prostate cancer: results decisively determined by the cut-off time-point chosen for the analysis. Eur J Cancer 2001, 37:1768–1774.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    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 randomized trial. Lancet 2002, 360:103–108. A randomized clinical trial that shows a clear survival benefit for patients with stage T1-2 of WHO grade 3 or stage T3-4 N0-1 M0 prostate cancers who receive radiotherapy plus early treatment with goserelin for 3 years.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    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, 159:2030–2034.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Pilepich MV, Caplan R, Byhardt RW, et al.: Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group protocol 85-31. J Clin Oncol 1997, 15:1013–1021.

    PubMed  CAS  Google Scholar 

  31. 31.

    Pilepich MV, Winter K, Lawton C, et al.: Phase III trial of androgen suppression adjuvant to definitive radiotherapy: long-term results of RTOG study 85-31 [Abstract]. Am Soc Clin Oncol 2003, 22:381A.

    Google Scholar 

  32. 32.

    Shipley WU, Lu JD, Pilepich MV, et al.: Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: a secondary analysis of the randomized protocol RTOG 86-10. Int J Radiat Oncol Biol Phys 2002, 54:1302–1310.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Horwitz EM, Winter K, Hanks GE, et al.: Subset analysis of RTOG 85-31 and 86-10 indicates an advantage for long-term vs. short-term adjuvant hormones for patients with locally advanced nonmetastatic prostate cancer treated with radiation therapy. Int J Radiat Oncol Biol Phys 2001, 49:947–956.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Ludgate CM, Lim JT, Wilson AG, et al.: Neoadjuvant hormone therapy and external beam radiation for localized prostate cancer: Vancouver Island Centre experience. Can J Urol 2000, 7:937–943.

    PubMed  CAS  Google Scholar 

  35. 35.

    Hanks GE, Lu JD, Machtay M, et al.: RTOG protocol 92-02: a phase III trial of the use of long-term total androgen suppression following neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate [Abstract]. Int J Radiat Oncol Biol Phys 2000, 48(suppl):112.

    Article  Google Scholar 

  36. 36.

    Schulman CC, Debruyne FM, Foster G, et al.: Four-year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. Eur Urol 2000, 38:706–713.

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Bono AV, Pagano F, Montironi R, et al.: Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian Prosit study. Urology 2001, 57:117–121.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Aus G, Abrahamsson PA, Ahlgren G, et al.: Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial. BJU Int 2002, 90:561–566.

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Soloway MS, Pareek K, Sharifi R, et al.: Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxM0 prostate cancer: 5-year results. J Urol 2002, 167:112–116.

    PubMed  Article  Google Scholar 

  40. 40.

    Klotz LH, Goldenberg SL, Jewett MA, et al.: Long-term followup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy. J Urol 2003, 170:791–794.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Gleave ME, Goldenberg SL, Chin JL, et al.: Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects. J Urol 2001, 166:500–507.

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Gleave ME, Goldenberg L, Chin JL, et al.: Randomized comparative study of 3 vs 8 months of neoadjuvant hormonal therapy prior to radical prostatectomy: 3-year PSA recurrence rates [Abstract]. J Urol 2003, 169(suppl 4):179.

    Google Scholar 

  43. 43.

    DeKernion JB, Neuwirth H, Stein A, et al.: Prognosis of patients with stage D1 prostate carcinoma following radical prostatectomy with and without early endocrine therapy. J Urol 1990, 144:700–703.

    PubMed  CAS  Google Scholar 

  44. 44.

    Zincke H, Bergstralh EJ, Larson-Keller JJ, et al.: Stage D1 prostate cancer treated by radical prostatectomy and adjuvant hormonal treatment. Cancer 1992, 70:311–323.

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Messing EM, Manola J, Sarosdy M, et al.: Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999, 341:1781–1788. A randomized prospective trial indicating that immediate adjuvant androgen ablation provides a highly significant survival benefit in patients with node-positive prostate cancer following radical prostatectomy and pelvic lymphadenectomy.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Walsh PC, DeWeese TL, Eisenberger MA: A structures debate. Immediate versus deferred androgen suppression in prostate cancer: evidence for deferred treatment. J Urol 2001, 166:508–516.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Cadeddu JA, Partin AW, Epstein JI, Walsh PC: Stage D1 (T1-3, N1-3, M0) prostate cancer: a case-controlled comparison of conservative treatment versus radical prostatectomy. Urology 1997, 50:251–255.

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Seay TM, Blute ML, Zincke H: Long-term outcome in patients with pTxN+ adenocarcinoma of prostate treated with radical prostatectomy and early androgen ablation. J Urol 1998, 159:357–364.

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    Messing EM: Editorial comment. J Urol 2001, 166:515–516.

    Article  Google Scholar 

  50. 50.

    Messing EM, Manola J, Sarosdy M, et al.: Immediate hormonal therapy versus observation after radical prostatectomy and pelvic lymphadenectomy for node positive prostate cancer: at 10 years results of EST 3886 [Abstract]. J Urol 2004, in press.

  51. 51.

    Wirth M, Frohmüller H, Marx F, et al.: Randomized multicenter trial on adjuvant flutamide therapy in locally advanced prostate cancer after radical surgery: interim analysis of treatment effect and prognostic factors [Abstract]. Br J Urol 1997, 80(suppl 2):263.

    Google Scholar 

  52. 52.

    See WA, Wirth MP, McLeod DG, et al.: Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program. J Urol 2003, 168:429–435.

    Article  Google Scholar 

  53. 53.

    Kaisary AV, Tyrrell CJ, Peeling WB, Griffiths K: Comparison of LHRH analogue (Zoladex) with orchiectomy in patients with metastatic prostatic carcinoma. Br J Urol 1991, 67:502–508.

    PubMed  CAS  Article  Google Scholar 

  54. 54.

    Vogelzang NJ, Chodak GW, Soloway MS, et al.: Goserelin versus orchiectomy in the treatment of advanced prostate cancer: final results of a randomized trial. Urology 1995, 46:220–226.

    PubMed  Article  CAS  Google Scholar 

  55. 55.

    Clark JA, Wray NP, Ashton CM: Living with treatment decisions: regrets and quality of life among men treated for metastatic prostate cancer. J Clin Oncol 2001, 19:72–80.

    PubMed  CAS  Google Scholar 

  56. 56.

    Prostate Cancer Trialists’ Collaborative Group: Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet 2000, 355:1491–1498.

    Article  Google Scholar 

  57. 57.

    Schmitt B, Wilt TJ, Schellhammer PF, et al.: Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: a systematic review. Urology 2001, 57:727–732.

    PubMed  Article  CAS  Google Scholar 

  58. 58.

    Pound CR, Partin AW, Eisenberger MA, et al.: Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999, 281:1591–1597.

    PubMed  Article  CAS  Google Scholar 

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Miyamoto, H., Messing, E.M. Early versus late hormonal therapy for prostate cancer. Curr Urol Rep 5, 188–196 (2004). https://doi.org/10.1007/s11934-004-0036-4

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Keywords

  • Prostate Cancer
  • Hormonal Therapy
  • Radical Prostatectomy
  • Radiat Oncol Biol Phys
  • Radiation Therapy Oncology Group