Hormonal therapy has been the standard for advanced prostate cancer for over 60 years. Recently, the utility of androgen ablation through various means has been demonstrated for earlier stages of disease. In particular, the strongest evidence to date involves the use of hormonal therapy in combination with radiation therapy. In this article we review the basic concepts in hormonal ablation for prostate cancer and review the evidence-based studies that support the use of hormonal therapy in early stage prostate cancer.
Abrahamsson, P.A. ( 2010) Potential benefits of intermittent androgen suppression therapy in the treatment of prostate cancer: a systematic review of the literature . Eur Urol57: 49-59.
2.
Akaza, H., Hinotsu, S., Usami, M., Arai, Y., Kanetake, H., Naito, S. et al. (2009) Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer115: 3437-3445.
3.
Arai, Y., Akaza, H., Deguchi, T., Fujisawa, M., Hayashi, M., Hirao, Y. et al. (2008) Evaluation of quality of life in patients with previously untreated advanced prostate cancer receiving maximum androgen blockade therapy or LHRHa monotherapy: a multicenter, randomized, doubleblind, comparative study. J Cancer Res Clin Oncol134: 1385-1396.
4.
Aus, G., Abrahamsson, P.A., Ahlgren, G., Hugosson, J., Lundberg, S., Schain, M. et al. (2002) Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial . BJU Int90: 561-566.
5.
Bolla, M., Collette, L., Blank, L., Warde, P., Dubois, J.B., Mirimanoff, R.O. et al. (2002) 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. Lancet360: 103-106.
6.
Bolla, M., de Reijke, T.M., Van Tienhoven, G., Van den Bergh, A.C., Oddens, J., Poortmans, P.M. et al. (2009) Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med360: 2516-2527.
7.
Bolla, M., Gonsalez, D., Warde, P., Dubois, J.B., Mirimanoff, R.O., Storme, G. et al. (1997) Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med337: 295-300.
8.
Calais da Silva, F.E., Bono, A.V., Whelan, P., Brausi, M., Marques Queimadelos, A., Martin, J.A. et al. (2009) Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European Uroncological Group. Eur Urol55: 1269-1277.
9.
Cooperberg, M.R., Grossfeld, G.D., Lubeck, D.P. and Carroll, P.R. ( 2003) National practice patterns and time trends in androgen ablation for localized prostate cancer. J Natl Cancer Inst95: 981-989.
10.
Crook, J., Ludgate, C., Malone, S., Perry, G., Eapen, L., Bowen, J. et al. (2009) Final report of multicenter Canadian phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional dose radiotherapy for clinically localized prostate cancer. Int J Radiation Oncology Biol Phys73: 327-333.
11.
D’Amico, A.V., Chen, M., Renshaw, A.A., Loffredo, M. and Kantoff, P.W. ( 2008) Androgen suppression and radiation vs radiation alone for prostate cancer, a randomized trial. JAMA299: 289-295.
12.
D’Amico, A.V., Schultz, D., Loffredo, M., Dugal, R., Hurwitz, M., Kaplan, I. et al. (2000) Biochemical outcome following external beam radiation therapy with or without androgen suppression therapy for clinically localized prostate cancer. JAMA284: 1280-1283.
13.
de Leval, J., Boca, P., Yousef, E., Nicolas, H., Jeukenne, M., Bouffioux, C. et al. (2002) Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naive prostate cancer: results of a prospective randomized multicenter trial. Clin Prostate Cancer1: 163-171.
14.
Debruyne, F.M. and Witjes, W.P. ( 2000) Neoadjuvant hormonal therapy prior to radical prostatectomy: theEuropean experience. Mol Urol4: 251-256.
15.
Denham, J.W., Steigler, A., Lamb, D.S., Joseph, D., Mameghan, H., Turner, S. et al. (2005) 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 Oncol6: 841-850.
16.
Fair, W.R., Rabbani, F., Bastar, A. and Betancourt, J. ( 1999) Neoadjuvant hormone therapy before radical prostatectomy. Update on the Memorial Sloan-Kettering Cancer Center Trials. Mol Urol3: 253-309.
17.
Freedland, S.J., Eastham, J. and Shore, N.(2009) Androgen deprivation therapy and estrogen deficiency induced adverse effects in the treatment of prostate cancer. Prostate Cancer Prostatic Dis12: 333-338.
18.
Galvao, D.A., Taaffe, D.R., Spry, N., Joseph, D. and Newton, R.U. ( 2009) Cardiovascular and metabolic complications during androgen deprivation: exercise as a potential countermeasure. Prostate Cancer Prostatic Dis12: 233-240.
19.
Gleave, M.E., Goldenberg, S.L., Chin, J.L., Warner, J., Saad, F., Klotz, L.H. et al. (2001) Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects. J Urol166: 500-506.
20.
Gomella, L.G. ( 2007) Global update on the use of hormonal therapy for the management of high-risk prostate cancer: Introduction. BJU Int99(Suppl 1): 1.
21.
Horwitz, E.M., Bae, K., Hanks, G.E., Porter, A., Grignon, D.J., Brereton, H.D. et al. (2008) 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 Oncol26: 2497-2504.
22.
Huggins, C. and Hodges, C.V. ( 1941) Studies on prostate cancer: the effect of castration of estrogen and androgen injection on serum phosphatase in metastatic carcinoma of the prostate. Cancer Res1: 293.
23.
Joon, D.L., Hasegawa, M., Sikes, C., Khoo, V.S., Terry, N.H., Zagars, G.K. et al. (1997) Supra-additive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation. Int J Radiat Oncol Biol Phys38: 1071-1077.
24.
Klotz, L., Boccon-Gibod, L., Shore, N.D., Andreou, C., Persson, B.E., Cantor, P. et al. (2008) The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int102: 1531-1538.
25.
Klotz, L.H., Goldenberg, S.L., Jewett, M.A., Fradet, Y., Nam, R., Barkin, J. et al. (2003) Long-term followup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy . J Urol170: 791-794.
26.
Langenhuijsen, J.F., van Lin, E.N., Hoffman, A.L., Spitter-Post, I., Alfred Witjes, J., Kaander, J.H. et al. (2010) Neoadjuvant androgen deprivation for prostate volume reduction: The optimal duration in prostate cancer radiotherapy. Urol Oncol (in press).
27.
Lawton, C.A., Desilvio, M., Roach III, M., Uhl, V., Kirsch, R., Seider, M. et al. (2007) An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys69: 646-655.
28.
Malone, S., Perry, G., Segal, R., Dahrouge, S. and Crook, J. ( 2005) Long-term side-effects of intermittent androgen suppression therapy in prostate cancer: results of a phase II study. BJU Int96: 514-520.
29.
McLeod, D.G., Iversen, P., See, W.A., Morris, T., Armstrong, J., Wirth, M.P. et al. (2006) Bicalutamide 150 mg plus standard care vs. standard care alone for early prostate cancer. BJU Int97: 247-254.
30.
Messing, E.M., Manola, J., Sarosdy, M., Wilding, G., Crawford, E.D. and Trump, D. ( 1999) Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med341: 1781-1788.
31.
Messing, E.M., Manola, J., Yao, J., Kieman, M., Crawford, D., Wilding, G. et al. (2006) Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol7: 472-479.
32.
Milecki, P., Baczyk, M., Skowronek, J., Antczak, A., Kwias, Z. and Martenka, P. ( 2009) Benefit of whole pelvic radiotherapy combined with neoadjuvant androgen deprivation for the high-risk prostate cancer. J Biomed Biotechnol2009: 625394.
33.
Mottet, N., Goussard, M., Loulidi, S. and Wolff, J. ( 2009) Intermittent versus continuous maximal androgen blockade in metastatic (D2) prostate cancer patients. A randomized trial. Paper presented at the 24th Congress of the European Association of Urology.
34.
Pilepich, M.V., Winter, K., John, M.J., Mesic, J.B., Sause, W., Rubin, P. et al. (2001) Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys50: 1243-1252.
35.
Pilepich, M.V., Winter, K., Lawton, C.A., Krisch, R.E., Wolkov, H.B., Movsas, B. et al. (2005) Androgen suppression adjuvant to radiotherapy in carcinoma of the prostate. Long-term results of phase III RTOG study 85-31 . Int J Radiat Oncol Biol Phys61: 1285-1290.
36.
Population Division, U.S. Census Bureau (2010 ) Projections of the Population by Selected Age Groups and Sex for the United States: 2010 to 2050. http://www.census.gov/population/www./projections/summarytables.html.
37.
Prostate Cancer Trialists’ Collaborative Group ( 2000) Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet355: 1491-1498.
38.
Roach III, M., Bae, K., Speight, J., Wolkov, H.B., Rubin, P., Lee, R.J. et al. (2008) Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol26: 585-591.
39.
Roach III, M., DeSilvio, M., Lawton, C.A., Uhl, V., Machtay, M., Seider, M.J. et al. (2003) Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 94-13. J Clin Oncol21: 1904-1911.
40.
Saigal, C.S., Gore, J.L., Krupski, T.L., Hanley, J., Schonlau, M., Litwin, M.S. et al. (2007) Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer110: 1493-1500.
41.
Sandler, H.M. ( 2004) Optimizing hormone therapy in localized prostate cancer: focus on external beam radiotherapy. J Urol172: S38-S41.
42.
Schulman, C.C., Debruyne, F.M., Forster, G., Selvaggi, F.P., Zlotta, A.R. and Witjes, W.P. ( 2000) 4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer. Eur Urol38: 706-713.
43.
Seruga, B. and Tannock, I.F. ( 2008) The changing face of hormonal therapy for prostate cancer . Ann Oncol19(Suppl 7): vii79-85.
44.
Shahinian, V.B., Kuo, Y.F., Freeman, J.L. and Goodwin, J.S. ( 2005) Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med352: 154-164.
45.
Shelley, M.D., Kumar, S., Coles, B., Wilt, T., Staffurth, J. and Mason, M.D.(2009) Adjuvant hormone therapy for localised and locally advanced prostate carcinoma: a systematic review and meta-analysis of randomised trials. Cancer Treat Rev35: 540-546.
46.
Soloway, M.S., Pareek, K., Sharifi, R., Wajsman, Z., McLeod, D., Wood Jr, D.P. et al. (2002) Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results. J Urol167: 112-116.
47.
Thompson, I., Thrasher, J.B., Aus, G., Burnett, A.L., Canby-Hagino, E.D., Cookson, M.S. et al. (2007) Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol177: 2106-2131.
48.
Vallet, B.S. ( 1944) Radical perineal prostatectomy subsequent to bilateral orchiectomy. Del Med J16: 18-20.
49.
Widmark, A., Klepp, O., Solberg, A., Damber, J.E., Angelsen, A., Fransson, P. et al. (2009) Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet373: 301-308.
50.
Witjes, W.P., Schulman, C.C. and Debruyne, F.M. ( 1997) Preliminary results of a prospective randomized study comparing radical prostatectomy versus radical prostatectomy associated with neoadjuvant hormonal combination therapy in T2-3,N0,M0 prostatic carcinoma. The European Study Group on Neoadjuvant Treatment of Prostate Cancer. Urology49(3A Suppl): 65-69.
51.
Yee, D.S., Lowrance, W.T., Eastham, J.A., Maschino, A.C., Cronin, A.M., Rabbani, F. et al. (2010) Long-term follow-up of 3-month neoadjuvant hormone therapy before radical prostatectomy in a randomized trial. BJU Int105: 185-190.
52.
Zietman, A.L., Prince, E.A., Nakfoor, B.M. and Park, J.J. ( 1997) Androgen deprivation and radiation therapy: sequencing studies using the Shionogi in vivo tumor system. Int J Radiat Oncol Biol Phys38: 1067-1070.