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


      To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer.

      Methods and Materials

      Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3–189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6–10.1). Of the 378 patients, 361 were evaluable, and 290 were still living.


      The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01).


      A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.
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        • Denham J.W.
        • Steigler A.
        • Lamb D.S.
        • 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: 841-850
        • Roach III, 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 8610.
        J Clin Oncol. 2008; 26: 585-591
        • 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: 103-106
        • Pilepich M.V.
        • Winter K.
        • Lawton C.A.
        • 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: 1285-1290
        • Hanks G.E.
        • Pajak T.F.
        • Porter A.
        • et al.
        Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: The Radiation Therapy Oncology Group protocol 92-02.
        J Clin Oncol. 2003; 21: 3972-3978
        • D'Amico A.V.
        • Manola J.
        • Loffredo M.
        • et al.
        6-Month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: A randomized controlled trial.
        JAMA. 2004; 292: 821-827
        • D'Amico A.V.
        • Denham J.W.
        • 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: 2420-2425
        • Keating N.L.
        • O'Malley A.J.
        • Smith M.R.
        Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer.
        J Clin Oncol. 2006; 24: 4448-4456
        • Tsai H.K.
        • D'Amico A.V.
        • Sadetsky N.
        • et al.
        Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality.
        J Natl Cancer Inst. 2007; 99: 1516-1524
        • Goldenberg S.L.
        • Klotz L.H.
        • Srigley J.
        • et al.
        • Canadian Urologic Oncology Group
        Randomized, prospective, controlled study comparing radical prostatectomy alone and neoadjuvant androgen withdrawal in the treatment of localized prostate cancer.
        J Urol. 1996; 156: 873-877
        • Labrie F.
        • Dupont A.
        • Cusan L.
        • et al.
        Downstaging of localized prostate cancer by neoadjuvant therapy with flutamide and Lupron: The first controlled and randomized trial.
        Clin Invest Med. 1993; 16: 499-509
        • Soloway M.S.
        • Sharifi R.
        • Wajsman Z.
        • et al.
        • Lupron Depot Neoadjuvant Prostate Cancer Study Group
        Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer.
        J Urol. 1995; 154: 424-428
        • Sobin L.H.
        • Wittekind C.
        • International Union Against Cancer
        TNM classification of malignant tumours.
        5th ed. John Wiley & Sons, New York1997
        • D'Amico A.V.
        • Whittington R.
        • Malkowicz S.B.
        • et al.
        Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer.
        JAMA. 1998; 280: 969-974
        • Crook J.
        • Ludgate C.
        • Malone S.
        • et al.
        Report of a multicenter Canadian phase III randomized trial of 3 months vs. 8 months neoadjuvant androgen deprivation before standard-dose radiotherapy for clinically localized prostate cancer.
        Int J Radiat Oncol Biol Phys. 2004; 60: 15-23
        • Roach III, M.
        • Hanks G.
        • Thames Jr., H.
        • et al.
        Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference.
        Int J Radiat Oncol Biol Phys. 2006; 65: 965-974
        • Gleave M.E.
        • Goldenberg S.L.
        • Jones E.C.
        • et al.
        Biochemical and pathological effects of 8 months of neoadjuvant androgen withdrawal therapy before radical prostatectomy in patients with clinically confined prostate cancer.
        J Urol. 1996; 155: 213-219
        • Gleave M.E.
        • Goldenberg S.L.
        • Chin J.L.
        • 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
        • Pollack A.
        • Zagars G.K.
        • Starkschall G.
        • et al.
        Prostate cancer radiation dose response: Results of the M.D. Anderson phase III randomized trial.
        Int J Radiat Oncol Biol Phys. 2002; 53: 1097-1105
        • Pilepich M.V.
        • Winter K.
        • John M.J.
        • et al.
        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 Phys. 2001; 50: 1243-1252
        • Bolla M.
        • van Tienhoven G.
        • de Reijke T.M.
        • et al.
        Concomitant and adjuvant androgen deprivation (ADT) with external beam irradiation (RT) for locally advanced prostate cancer: 6 months versus 3 years ADT—Results of the randomized EORTC Phase III trial 22961.
        J Clin Oncol. 2007; 25: 5014
        • Dearnaley D.P.
        • Hall E.
        • Lawrence D.
        • et al.
        Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects.
        Br J Cancer. 2005; 92: 488-498
        • Merrick G.S.
        • Butler W.M.
        • Wallner K.E.
        • et al.
        Impact of supplemental external beam radiotherapy and/or androgen deprivation therapy on biochemical outcome after permanent prostate brachytherapy.
        Int J Radiat Oncol Biol Phys. 2005; 61: 32-43
        • Potters L.
        • Torre T.
        • Ashley R.
        • et al.
        Examining the role of neoadjuvant androgen deprivation in patients undergoing prostate brachytherapy.
        J Clin Oncol. 2000; 18: 1187-1192
        • Lee L.N.
        • Stock R.G.
        • Stone N.N.
        Role of hormonal therapy in the management of intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation.
        Int J Radiat Oncol Biol Phys. 2002; 52: 444-452
        • Beyer D.C.
        • McKeough T.
        • Thomas T.
        Impact of short course hormonal therapy on overall and cancer-specific survival after permanent prostate brachytherapy.
        Int J Radiat Oncol Biol Phys. 2005; 61: 1299-1305
        • Ludgate C.M.
        • Lim J.T.
        • Wilson A.G.
        • et al.
        Neoadjuvant hormone therapy and external beam radiation for localized prostate cancer: Vancouver Island Cancer Centre experience.
        Can J Urol. 2000; 7: 937-943


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