Patient-reported outcomes after Low-dose-rate versus High-dose-rate brachytherapy boost in combination with external beam radiation for intermediate and high risk prostate cancer



      Addition of a brachytherapy boost to external beam radiation therapy (EBRT) reduces prostate cancer (PCa) recurrence at the expense of genitourinary (GU) toxicity. Whether brachytherapy boost technique, specifically low-dose-rate (LDR-BT) versus high-dose-rate (HDR-BT), impacts treatment-related toxicity is unclear.


      Between 2012-2018, 106 men with intermediate/high risk PCa underwent EBRT (37.5-45 Gy in 1.8-2.5 Gy/fraction) plus brachytherapy boost, either with LDR-BT (110 Gy I-125 or 100 Gy Pd-103; n = 51) or HDR-BT (15 Gy x1 Ir-192; n = 55). Patient-reported outcomes (PRO) were assessed by International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC-CP) surveys at 3-6-month intervals for up to three years following treatment, with higher scores indicating more severe toxicity. Provider-reported GU and gastrointestinal (GI) toxicity was graded per CTCAE v5.0 at each follow-up. Linear mixed models comparing PROs between LDR-BT versus HDR-BT were fitted. Stepwise multivariable analysis (MVA) was performed to account for age, gland size, androgen deprivation therapy use, and alpha-blocker medication use. Incidence rates of grade 2+ GU/GI toxicity was compared using Fisher's exact test.


      Use of LDR-BT was associated with greater change in IPSS (p=0.003) and EPIC-CP urinary irritative score (p = 0.002) compared with HDR-BT, but effect size diminished over time (LDR-BT versus HDR-BT: baseline to 6-/24-month mean IPSS change, +6.4/+1.4 versus +2.7/-3.0, respectively; mean EPIC-CP irritative/obstructive change, +2.5/+0.1 versus +0.9/+0.1, respectively). Results remained significant on MVA. Post-treatment grade 2+ GU toxicity was significantly higher in the LDR-BT group (67.5% versus 42.9% for LDR-BT and HDR-BT, respectively; p <0.001). There were no differences between groups in incontinence, bowel function, and erectile function, or grade 2+ GI toxicity.


      Compared with LDR-BT, HDR-BT was associated with lower acute patient- and provider-reported GU toxicity.


      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 Brachytherapy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Michalski J.M.
        • Moughan J.
        • Purdy J.
        • Bosch W.
        • et al.
        Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer.
        JAMA Oncology. 2018; 4e180039
        • Kuban D.A.
        • Tucker S.L.
        • Dong L.
        • Starkschall G.
        • et al.
        Long-Term Results of the M. D. Anderson Randomized Dose-Escalation Trial for Prostate Cancer.
        International Journal of Radiation Oncology*Biology*Physics. 2008; 70: 67-74
        • Spratt D.E.
        • Michalski J.M.
        Long-Term Benefits of Dose-Escalation in Localized Prostate Cancer.
        International Journal of Radiation Oncology*Biology*Physics. 2019; 104: 798-800
        • Morris W.J.
        • Tyldesley S.
        • Rodda S.
        • Halperin R.
        • et al.
        Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost f.
        International Journal of Radiation Oncology*Biology*Physics. 2017; 98: 275-285
        • Denham J.W.
        • Joseph D.
        • Lamb D.S.
        • Spry N.A.
        • et al.
        Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): 10-year results from a randomised, phase 3.
        Lancet Oncol. 2019; 20: 267-281
        • Brand D.H.
        • Tree A.C.
        • Ostler P.
        • van der Voet H.
        • et al.
        Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial.
        Lancet Oncol. 2019; 20: 1531-1543
        • Lukka H.R.
        • Pugh S.L.
        • Bruner D.W.
        • Bahary J.P.
        • et al.
        Patient Reported Outcomes in NRG Oncology RTOG 0938, Evaluating Two Ultrahypofractionated Regimens for Prostate Cancer.
        Int J Radiat Oncol Biol Phys. 2018; 102: 287-295
        • Taussky D.
        • Moumdjian C.
        • Larouche R.
        • Béliveau- D.
        • et al.
        Seed migration in prostate brachytherapy depends on experience and technique.
        Brachytherapy. 2012; 11: 452-456
        • Chauveinc L.
        • Osseili A.
        • Flam T.
        • Thiounn N.
        • et al.
        Migration des grains d'iode 125 après curiethérapie prostatique : étude d'une série de 170 patients.
        Cancer Radiothérapie. 2004; 8: 211-216
        • McLaughlin P.
        • Narayana V.
        • Pan C.
        • Berri S.
        • et al.
        Comparison of day 0 and day 14 dosimetry for permanent prostate implants using stranded seeds.
        Int J Radiat Oncol Biol Phys. 2006; 64: 144-150
        • Davis B.J.
        • Taira A.V.
        • Nguyen P.L.
        • Assimos D.G.
        • et al.
        ACR appropriateness criteria: Permanent source brachytherapy for prostate cancer.
        Brachytherapy. 2017; 16: 266-276
        • Hoskin P.J.
        • Rojas A.M.
        • Bownes P.J.
        • Lowe G.J.
        • et al.
        Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer.
        Radiotherapy and Oncology. 2012; 103: 217-222
        • Press R.H.
        • Morgan T.M.
        • Cutrell P.K.
        • Zhang C.
        • et al.
        Patient-reported health-related quality of life outcomes after HDR brachytherapy between small (<60 cc) and large (≥60 cc) prostate glands.
        Brachytherapy. 2019; 18: 13-21
        • Morton G.C.
        • Loblaw D.A.
        • Sankreacha R.
        • Deabreu A.
        • et al.
        Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Men With Intermediate-Risk Prostate Cancer: Analysis of Short- and Medium-Term Toxicity and Quality of Life.
        Int J Radiat Oncol Biol Phys. 2010; 77: 811-817
        • Demanes D.J.
        • Rodriguez R.R.
        • Schour L.
        • Brandt D.
        • et al.
        High-dose-rate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California endocurietherapy's 10-year results.
        Int J Radiat Oncol Biol Phys. 2005; 61: 1306-1316
        • Fischer-Valuck B.W.
        • Gay H.A.
        • Patel S.
        • Baumann B.C.
        • et al.
        A Brief Review of Low-Dose Rate (LDR) and High-Dose Rate (HDR) Brachytherapy Boost for High-Risk Prostate.
        Frontiers in Oncology. 2019; : 9
      1. Services, U.D.o.H.a.H.Common Terminology Criteria for Adverse Events (CTCAE). V4.03. 2010 [cited 2019; Available from:

        • Barry M.J.
        • Fowler Jr., F.J.
        • O'Leary M.P.
        • Bruskewitz R.C.
        • et al.
        The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association.
        J Urol. 1992; 148 (discussion 1564): 1549-1557
        • Chang P.
        • Szymanski K.M.
        • Dunn R.L.
        • Chipman J.J.
        • et al.
        Expanded prostate cancer index composite for clinical practice: development and validation of a practical health related quality of life instrument for use in the routine clinical care of patients with prostate cancer.
        J Urol. 2011; 186: 865-872
        • Norman GR
        • Sloan JA
        • Wyrwich KW.
        Interpretation of changes in health-related quality of life. The remarkable universality of half a standard deviation.
        Med Care. 2003; 41: 582-592
        • Hsu I.C.J.
        • Rodgers J.
        • Shinohara K.
        • Purdy J.A.
        • et al.
        Long-Term Results of NRG Oncology/RTOG 0321 A Phase II Trial of Combined High Dose Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate.
        International Journal of Radiation Oncology*Biology*Physics. 2019; 105: S57
        • Hoskin P.J.
        • Rojas A.M.
        • Ostler P.J.
        • Bryant L.
        • et al.
        Randomised trial of external-beam radiotherapy alone or with high-dose-rate brachytherapy for prostate cancer: Mature 12-year results.
        Radiother Oncol. 2021; 154: 214-219
        • Lessard E.
        • Pouliot J.
        Inverse planning anatomy-based dose optimization for HDR-brachytherapy of the prostate using fast simulated annealing algorithm and dedicated objective function.
        Med Phys. 2001; 28: 773
        • White E.C.
        • Kamrava M.R.
        • Demarco J.
        • Park S.J.
        • et al.
        High-dose-rate prostate brachytherapy consistently results in high quality dosimetry.
        Int J Radiat Oncol Biol Phys. 2013; 85: 543-548
        • Moorrees J.
        • Lawson J.M.
        • Marcu L.G.
        Assessment of I-125 seed implant accuracy when using the live-planning technique for low dose rate prostate brachytherapy.
        Radiation Oncology. 2012; 7: 196
        • Skowronek J.
        Review article Low-dose-rate or high-dose-rate brachytherapy in treatment of prostate cancer – between options.
        Journal of Contemporary Brachytherapy. 2013; 1: 33-41
        • Flam T.A.
        • Peyromaure M.
        • Chauveinc L.
        • Thiounn N.
        • et al.
        Post-brachytherapy transurethral resection of the prostate in patients with localized prostate cancer.
        J Urol. 2004; 172: 108-111
        • Slevin F
        • Rodda SL
        • Bownes P
        • et al.
        A comparison of outcomes for patients with intermediate and high risk prostate cancer treated with low dose rate and high dose rate brachytherapy in combination with external beam radiotherapy.
        Clin Transl Radiat Oncol. 2020; 20: 1-8
        • Rodda S.
        • Tyldesley S.
        • Morris W.J.
        • Keyes M.
        • 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.
        International Journal of Radiation Oncology*Biology*Physics. 2017; 98: 286-295
        • Joseph D.
        • Denham J.W.
        • Steigler A.
        • Lamb D.S.
        • et al.
        Radiation Dose Escalation or Longer Androgen Suppression to Prevent Distant Progression in Men With Locally Advanced Prostate Cancer: 10-Year Data From the TROG 03.04 RADAR Trial.
        International Journal of Radiation Oncology*Biology*Physics. 2020; 106: 693-702
        • Whalley D.
        • Hruby G.
        • Alfieri F.
        • Kneebone A.
        • et al.
        SpaceOAR Hydrogel in Dose-escalated Prostate Cancer Radiotherapy: Rectal Dosimetry and Late Toxicity.
        Clin Oncol (R Coll Radiol). 2016; 28: e148-e154
        • Karsh L.I.
        • Gross E.T.
        • Pieczonka C.M.
        • Aliotta P.J.
        • et al.
        Absorbable Hydrogel Spacer Use in Prostate Radiotherapy: A Comprehensive Review of Phase 3 Clinical Trial Published Data.
        Urology. 2018; 115: 39-44
        • Olsson C.E.
        • Alsadius D.
        • Pettersson N.
        • Tucker S.L.
        • et al.
        Patient-reported sexual toxicity after radiation therapy in long-term prostate cancer survivors.
        British Journal of Cancer. 2015; 113: 802-808
        • Mabjeesh N.
        • Chen J.
        • Beri A.
        • Stenger A.
        • et al.
        Sexual function after permanent 125I-brachytherapy for prostate cancer.
        International Journal of Impotence Research. 2005; 17: 96-101
        • Ragab O.
        • Banerjee R.
        • Park S.J.
        • Patel S.
        • et al.
        Comparison of patient-reported acute urinary and sexual toxicity scores in a 6- versus 2-fraction course of high-dose-rate prostate brachytherapy monotherapy.
        J Med Imaging Radiat Oncol. 2018; 62: 109-115
        • Donovan K.A.
        • Gonzalez B.D.
        • Nelson A.M.
        • Fishman M.N.
        • et al.
        Effect of androgen deprivation therapy on sexual function and bother in men with prostate cancer: A controlled comparison.
        Psycho-Oncology. 2018; 27: 316-324