Randomised trial of external-beam radiotherapy alone or with high-dose-rate brachytherapy for prostate cancer: Mature 12-year results

Published:October 01, 2020DOI:


      • 12 year results confirm HDR boost improves prostate cancer relapse free survival.
      • No difference in overall survival is seen.
      • No excess toxicity is seen in the HDR boost arm.


      Background and purpose

      A randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma. Previous analysis, at median follow up of 85 months, demonstrated improved relapse free survival (RFS) with EBRT + HDR-BTb. This data has now been updated with a median follow up of 131 months.

      Materials and methods

      From December 1997 to August 2005, patients were assigned either to EBRT alone delivering 55 Gy in 20 fractions over 4 weeks or EBRT followed by a temporary high-dose-rate implant delivering 2 × 8·5 Gy over 24 h. The primary endpoint was RFS defined by a PSA rise ≥2.0 µg/l above nadir, clinical progression or death. Actuarial survival rates and Hazard Ratios (HRs) were calculated using the Kaplan–Meier method and Cox’s Proportional Hazard Model, respectively. Secondary endpoints were overall survival (OS), urinary and bowel toxicity.


      One hundred and six patients received EBRT alone and 110 EBRT + HDR-BTb. Median time to relapse was 137 months in the HDR-BTb arm compared to 82 months for EBRT alone (p = 0·01). A 27% risk of recurrence with EBRT alone was observed (p = 0·001), resulting in a 21% improvement in RFS at 12 years with EBRT + HDR-BTb. In multivariate analysis treatment arm, risk category and no androgen deprivation therapy were significant covariates for risk of relapse. Differences in overall survival were not significant.


      At 12 years there remains a significant improvement in RFS after EBRT + HDR-BTb; both treatments were equitoxic for severe late urinary and bowel events and urethral strictures.


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        • Al-Mamgani A.
        • van Putten W.L.
        • Heemsbergen W.D.
        • et al.
        Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer.
        Int J Radiat Oncol Biol Phys. 2008; 72: 980-988
        • Dearnaley D.P.
        • Sydes M.R.
        • Graham J.D.
        • et al.
        Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial.
        Lancet Oncol. 2007; 8: 475-487
        • 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.
        • DeSilvio M.L.
        • Slater J.D.
        • et al.
        Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial.
        JAMA. 2005; 294: 1233-1239
        • De Bari B.
        • Daidone A.
        • Alongi F.
        Is high dose rate brachytherapy reliable and effective treatment for prostate cancer patients? A review of the literature.
        Crit Rev Oncol Hematol. 2015; 94: 360-370
        • Demanes D.J.
        • Ghilezan M.I.
        High-dose-rate brachytherapy as monotherapy for prostate cancer.
        Brachytherapy. 2014; 13: 529-541
        • Hsu I.C.
        • Yamada Y.
        • Assimos D.G.
        • et al.
        ACR Appropriateness Criteria high-dose-rate brachytherapy for prostate cancer.
        Brachytherapy. 2014; 13: 27-31
        • Crook J.
        • Marban M.
        • Batchelar D.
        HDR Prostate Brachytherapy.
        Semin Radiat Oncol. 2019; 30: 49-60
        • Martinez A.A.
        • Gonzalez J.
        • Ye H.
        • et al.
        Dose escalation improves cancer-related events at 10 years for intermediate- and high-risk prostate cancer patients treated with hypofractionated high-dose-rate boost and external beam radiotherapy.
        Int J Radiat Oncol Biol Phys. 2011; 79: 363-370
        • Martinez A.A.
        • Gustafson G.
        • Gonzalez J.
        • et al.
        Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.
        Int J Radiat Oncol Biol Phys. 2002; 53: 316-327
        • Hoskin P.J.
        • Rojas A.M.
        • Bownes P.J.
        • et al.
        Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer.
        Radiother Oncol. 2012; 103: 217-222
        • Hoskin P.J.
        • Motohashi K.
        • Bownes P.
        • et al.
        High dose rate brachytherapy in combination with external beam radiotherapy in the radical treatment of prostate cancer: initial results of a randomised phase three trial.
        Radiother Oncol. 2007; 84: 114-120
        • Hoskin P.J.
        • Rojas A.M.
        • Ostler P.J.
        • et al.
        Quality of life after radical radiotherapy for prostate cancer: longitudinal study from a randomised trial of external beam radiotherapy alone or in combination with high dose rate brachytherapy.
        Clin Oncol (R Coll Radiol). 2013; 25: 321-327
        • Roach 3rd, 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
        • Dische S.
        • Warburton M.F.
        • Jones D.
        • et al.
        The recording of morbidity related to radiotherapy.
        Radiother Oncol. 1989; 16: 103-108
        • Sathya J.R.
        • Davis I.R.
        • Julian J.A.
        • et al.
        Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate.
        J Clin Oncol. 2005; 23: 1192-1199
        • Dayes I.S.
        • Parpia S.
        • Gilbert J.
        • et al.
        Long-term results of a randomized trial comparing iridium implant plus external beam radiation therapy with external beam radiation therapy alone in node-negative locally advanced cancer of the prostate.
        Int J Radiat Oncol Biol Phys. 2017; 99: 90-93
        • Astrom L.
        • Grusell E.
        • Sandin F.
        • et al.
        Two decades of high dose rate brachytherapy with external beam radiotherapy for prostate cancer.
        Radiother Oncol. 2018; 127: 81-87
        • Morton G.C.
        • Alrashidi S.M.
        High dose rate brachytherapy in high-risk localised disease - why do anything else?.
        Clin Oncol (R Coll Radiol). 2020; 32: 163-169
        • Rodda S.
        • Tyldesley S.
        • Morris W.J.
        • et al.
        ASCENDE-RT: an analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer.
        Int J Radiat Oncol Biol Phys. 2017; 98: 286-295
        • 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 randomised study.
        Lancet Oncol. 2010; 11: 1066-1073
        • Brenner D.J.
        • Martinez A.A.
        • Edmundson G.K.
        • et al.
        Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue.
        Int J Radiat Oncol Biol Phys. 2002; 52: 6-13
        • Fowler J.
        • Chappell R.
        • Ritter M.
        Is alpha/beta for prostate tumors really low?.
        Int J Radiat Oncol Biol Phys. 2001; 50: 1021-1031
        • Vogelius I.R.
        • Bentzen S.M.
        Dose response and fractionation sensitivity of prostate cancer after external beam radiation therapy: a meta-analysis of randomized trials.
        Int J Radiat Oncol Biol Phys. 2018; 100: 858-865