Original Research| Volume 143, P64-74, January 2021

Download started.


Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial

Published:December 03, 2020DOI:


      • The phase 3 study includes only patients with intermediate risk prostate cancer.
      • The addition of short-course hormonal therapy leads to improved outcomes.
      • Short-term ADT combined with lower dose of radiotherapy is feasible and yields to a better toxicity profile.



      The role of androgen deprivation therapy (ADT) in combination with radiotherapy (RT) in intermediate-risk prostate cancer (IRPC) remains controversial, particularly in patients receiving dose-escalated RT (DERT). We compared outcomes between patients with IRPC treated with ADT and two different doses of RT vs. RT alone.


      From December 2000 to September 2010, 600 patients with IRPC were randomised to a three-arm trial consisting of 6 months of ADT plus RT 70 Gy (ADT + RT70) vs. ADT plus a DERT of 76 Gy (ADT + DERT76) vs. DERT of 76 Gy alone (DERT76). Primary end-point was biochemical failure (BF), and secondary end-points were overall survival (OS) and toxicity. RT toxicity was assessed by Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria.


      With a median follow-up of 11.3 years (interquartile range: 10.9–11.7), patients receiving DERT76 alone, compared with patients receiving ADT + RT70 and ADT + DERT76, had higher rates of BF (32%, 18% and 14%, respectively, p < 0.001), higher rates of prostate cancer progression (12%, 4.5% and 3.3%, respectively, p = 0.001) and more deaths due to prostate cancer (6.5%, 3.0% and 1.5%, respectively, p = 0.03) with no significant difference seen between ADT + RT70 and ADT + DERT76. There was no significant difference in OS between the 3 arms. A higher dose of RT (76 Gy) increased late gastrointestinal (GI) toxicity grade ≥ II compared with lower dose (70 Gy) (16% vs 5.3%, p < 0.001) with no statistical difference for late genitourinary toxicity.


      In IRPC, the addition of 6 months of ADT to RT70 or DERT76 significantly improves BF and appears to decrease the risk of death from prostate cancer compared with DERT76 alone with no difference in OS. In the setting of IRPC, ADT plus RT 70 Gy yields effective disease control with a better GI toxicity profile.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • 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: 1066-1073
        • Mason M.D.
        • Parulekar W.R.
        • Sydes M.R.
        • et al.
        Final report of the intergroup randomized study of combined androgen-deprivation therapy plus radiotherapy versus androgen-deprivation therapy alone in locally advanced prostate cancer.
        J Clin Oncol. 2015; 33: 2143-2150
        • Laverdière J.
        • Nabid A.
        • De Bedoya L.D.
        • et al.
        The efficacy and sequencing of a short course of androgen suppression on freedom from biochemical failure when administered with radiation therapy for T2-T3 prostate cancer.
        J Urol. 2004; 171: 1137-1140
        • D'Amico A.V.
        • Chen M.H.
        • Renshaw A.A.
        • et al.
        Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial.
        JAMA. 2008; 299: 289-295
        • Jones C.U.
        • Hunt D.
        • McGowan D.G.
        • et al.
        Radiotherapy and short-term androgen deprivation for localized prostate cancer.
        N Engl J Med. 2011; 365: 107-118
        • Mohler J.
        • Bahnson R.R.
        • Boston B.
        • et al.
        NCCN clinical practice guidelines in oncology: prostate cancer.
        J Natl Compr Canc Netw. 2010; 8: 162-200
        • Cox J.D.
        • Stetz J.
        • Pajak T.F.
        Toxicity criteria of the radiation therapy oncology group (RTOG) and the European Organization for Research and treatment of cancer (EORTC).
        Int J Radiat Oncol Biol Phys. 1995; 31: 1341-1346
        • 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
        • Pollack A.
        • Zagars G.K.
        • Smith L.G.
        • et al.
        Preliminary results of a randomized dose-escalation study comparing 70 Gy to 78 Gy for the treatment of prostate cancer.
        J Clin Oncol. 2000; 18: 3904-3911
        • Ahnn S.
        • Anderson S.J.
        Sample size determination for comparing more than two survival distributions.
        Stat Med. 1995; 14: 2273-2282
        • Selvin S.
        Practical bio statistical methods.
        Duxbury Press, Boston1999
        • Meinert C.L.
        Clinical trials: design, conduct and analysis.
        Oxford University Press, New York1986
        • Benjamini Y.
        • Hochberg Y.
        Controlling the false discovery rate: a practical and powerful approach to multiple testing.
        J Roy Stat Soc B. 1995; 57: 289-300
        • Hou Z.
        • Li G.
        • Bai S.
        High dose versus conventional dose in external beam radiotherapy of prostate cancer: a meta-analysis of long-term follow-up.
        J Canc Res Clin Oncol. 2015; 141: 1063-1071
        • Kuban D.A.
        • Tucker S.L.
        • Dong L.
        • et al.
        Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer.
        Int J Radiat Oncol Biol Phys. 2008; 70: 67-74
        • Zietman A.L.
        • Bae K.
        • Slater J.D.
        • et al.
        Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from Proton Radiation Oncology Group/American College of Radiology 95-09.
        J Clin Oncol. 2010; 28: 1106-1111
        • Heemsbergen W.D.
        • Al-Mamgani A.
        • Slot A.
        • et al.
        Long-term results of the Dutch randomized prostate cancer trial: impact of dose-escalation on local, biochemical, clinical failure, and survival.
        Radiother Oncol. 2014; 110: 104-109
        • Beckendorf V.
        • Guerif S.
        • Le Prise E.
        • et al.
        70 Gy versus 80 Gy in localized prostate cancer: 5-year results of GETUG 06 randomized trial.
        Int J Radiat Oncol Biol Phys. 2011; 80: 1056-1063
        • Dearnaley D.P.
        • Jovic G.
        • Syndikus I.
        • et al.
        Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomized controlled trial.
        Lancet Oncol. 2014; 15: 464-473
        • Locke J.A.
        • Dal Pra A.
        • Supiot S.
        • et al.
        Synergistic action of image-guided radiotherapy and androgen deprivation therapy.
        Nat Rev Urol. 2015; 12: 193-204
        • Denham J.W.
        • Steigler A.
        • Lamb D.S.
        • 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: 451-459
        • Jones C.U.
        • Pugh S.
        • Sandler H.M.
        • et al.
        Long-term update of NRG oncology RTOG 94-08.
        Int J Radiat Oncol Biol Phys. 2018; 102: S31-S32
        • D'Amico A.V.
        • Chen M.H.
        • Renshaw A.A.
        • et al.
        Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial.
        JAMA. 2008; 299: 289-295
        • Bolla M.
        • Maingon P.
        • Carrie C.
        • et al.
        Short androgen suppression and radiation dose escalation for intermediate- and high-risk localized prostate cancer: results of EORTC trial 22991.
        J Clin Oncol. 2016; 34: 1748-1756
        • Amini A.
        • Rusthoven C.G.
        • Jones B.L.
        • et al.
        Survival outcomes of radiotherapy with or without androgen-deprivation therapy for patients with intermediate-risk prostate cancer using the National Cancer Data Base.
        . 2016; 34: 165.e1-165.e9
        • Michalski J.M.
        • Moughan J.
        • Purdy J.
        • et al.
        Effect of standard vs dose-escalated radiation therapy for patients with intermediate-risk prostate cancer: the NRG oncology RTOG 0126 randomized clinical trial.
        JAMA Oncol. 2018; 4: e180039
        • Xie W.
        • Regan M.M.
        • Buyse M.
        • et al.
        Metastasis-free survival is a strong surrogate of overall survival in localized prostate cancer.
        J Clin Oncol. 2017; 35: 3097-3104
        • Pisansky T.M.
        • Hunt D.
        • Gomella L.G.
        • 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: 332-339
        • Pai H.H.
        • Pickles T.
        • Keyes M.
        • et al.
        Randomized study evaluating testosterone recovery using short-versus long-acting luteinizing hormone releasing hormone agonistsCan.
        Urol Assoc J. 2011; 5: 173-179
        • Zumsteg Z.S.
        • Spratt D.E.
        • Pei I.
        • et al.
        A new risk classification system for therapeutic decision making with intermediate-risk prostate cancer patients undergoing dose-escalated external-beam radiation therapy.
        Eur Urol. 2013; 64: 895-902
        • Berlin A.
        • Murgic J.
        • Hosni A.
        • et al.
        Genomic classifier for guiding treatment of intermediate-risk prostate cancers to dose-escalated image guided radiation therapy without hormone therapy.
        Int J Radiat Oncol Biol Phys. 2019; 103: 84-91

      Linked Article

      • Reply to comment on: Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial
        European Journal of CancerVol. 167
        • Preview
          The authors thank Drs. Guler and Onal for their interest in our article ‘Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial’ [1]. The authors think it is important to clarify some misunderstanding that Drs. Guler and Onal may have had when interpreting our results. In our study, in patients with only intermediate-risk prostate cancer (IRPC), the addition of a short course of androgen suppression therapy (ADT) to conventional fractionation radiotherapy to 70 Gy (RT70) or dose-escalated radiotherapy to 76 Gy did impact on biochemical control and prostate cancer specific mortality compared to dose-escalated radiotherapy alone (DERT76 Gy).
        • Full-Text
        • PDF
      • Re: Androgen deprivation therapy and radiotherapy in intermediate risk prostate cancer: A randomized phase III trial
        European Journal of CancerVol. 167
        • Preview
          The article by Nabid et al. [1] on the role of androgen deprivation therapy (ADT) in intermediate-risk prostate cancer (IRPC) with two different radiotherapy (RT) fractionation schemes piqued our interest. When compared to ADT plus conventional fractionation radiotherapy (RT70) and ADT plus dose escalated radiotherapy (DERT76), the DERT76 only arm had statistically significant higher rates of biochemical failure (BF), prostate cancer progression, and disease-related deaths. There was no statistically significant difference between patients who received ADT with conventional or dose-escalation RT.
        • Full-Text
        • PDF