Detection of failure patterns using advanced imaging in patients with biochemical recurrence following low-dose-rate brachytherapy for prostate cancer



      This study describes the pattern of failure in patients with biochemical (BCR) recurrence after low-dose-rate (LDR) brachytherapy as a component of definitive treatment for prostate cancer.


      Patients with BCR after LDR brachytherapy ± external beam radiation therapy (EBRT) were enrolled on prospective IRB approved advanced imaging protocols. Patients underwent 3T multiparametric MRI (mpMRI); a subset underwent prostate specific membrane antigen (PSMA)-based PET/CT. Pathologic confirmation was obtained unless contraindicated.


      Between January 2011 and April 2021, 51 patients with BCR after brachytherapy (n = 36) or brachytherapy + EBRT (n = 15) underwent mpMRI and were included in this analysis. Of 38 patients with available dosimetry, only two had D90<90%. The prostate and seminal vesicles were a site of failure in 66.7% (n = 34) and 39.2% (n = 20), respectively. PET/CT (n = 32 patients) more often identified lesions pelvic lymph nodes (50%; n = 16) and distant metastases (18.8%; n = 6), than mpMRI. Isolated nodal disease (9.8%; n = 5) and distant metastases (n = 1) without local recurrence were uncommon. Recurrence within the prostate was located in the transition zone in 48.5%, central or midline in 45.5%, and anterior in 36.4% of patients.


      In this cohort of patients with BCR after LDR brachytherapy ± EBRT, the predominant recurrence pattern was local (prostate ± seminal vesicles) with frequent occurrence in the anterior prostate and transition zone. mpMRI and PSMA PET/CT provided complementary information to localize sites of recurrence, with PSMA PET/CT often confirming mpMRI findings and identifying occult nodal or distant metastases.


      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


        • King M.T.
        • Keyes M.
        • Frank S.J.
        • et al.
        Low-dose-rate brachytherapy for primary treatment of localized prostate cancer: a systemic review and executive summary of an evidence-based consensus statement.
        Brachytherapy. 2021; 20: 1114-1129
        • Grimm P.
        • Billiet I.
        • Bostwick D.
        • et al.
        Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high-risk prostate cancer treatment by radical therapy. Results from the prostate cancer results study group.
        BJU Int. 2012; 109: 22-29
        • Zelefsky M.J.
        • Kuban D.A.
        • Levy L.B.
        • et al.
        Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation.
        Int J Radiat Oncol Biol Phys. 2007; 67: 327-333
        • Kittel J.A.
        • Reddy C.A.
        • Smith K.L.
        • et al.
        Long-term efficacy and toxicity of low-dose-rate ¹²⁵I prostate brachytherapy as monotherapy in low-, intermediate-, and high-risk prostate cancer.
        Int J Radiat Oncol Biol Phys. 2015; 92: 884-893
        • Potters L.
        • Morgenstern C.
        • Calugaru E.
        • et al.
        12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer.
        J Urol. 2008; 179: S20-S24
        • Stock R.G.
        • Cesaretti J.A.
        • Stone N.N.
        Disease-specific survival following the brachytherapy management of prostate cancer.
        Int J Radiat Oncol Biol Phys. 2006; 64: 810-816
        • Morris W.J.
        • Tyldesley S.
        • Rodda S.
        • 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 for high- and intermediate-risk prostate cancer.
        Int J Radiat Oncol Biol Phys. 2017; 98: 275-285
        • Spratt D.E.
        • Soni P.D.
        • McLaughlin P.W.
        • et al.
        American Brachytherapy Society Task Group Report: combination of brachytherapy and external beam radiation for high-risk prostate cancer.
        Brachytherapy. 2017; 16: 1-12
        • Stone N.N.
        • Skouteris V.
        • Stock R.G.
        Long-term biochemical control and cause-specific survival in men with Gleason grade Group 4 and 5 prostate cancer treated with brachytherapy and external beam irradiation.
        Brachytherapy. 2020; 19: 275-281
        • Stone N.N.
        • Potters L.
        • Davis B.J.
        • et al.
        Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy.
        Int J Radiat Oncol Biol Phys. 2009; 73: 341-346
        • Tetreault-Laflamme A.
        • Crook J.
        • Hamm J.
        • et al.
        Long-term prostate specific antigen stability and predictive factors of failure after permanent seed prostate brachytherapy.
        J Urol. 2018; 199: 120-125
        • Punnen S.
        • Cooperberg M.R.
        • D'Amico A.V.
        • et al.
        Management of biochemical recurrence after primary treatment of prostate cancer: a systematic review of the literature.
        Eur Urol. 2013; 64: 905-915
        • Stone N.N.
        • Unger P.
        • Crawford E.D.
        • Stock R.G.
        Diagnosis and management of local recurrence after low-dose-rate brachytherapy.
        Brachytherapy. 2015; 14: 124-130
        • Stone N.N.
        • Stock R.G.
        • White I.
        • Unger P.
        Patterns of local failure following prostate brachytherapy.
        J Urol. 2007; 177: 1759-1763
        • Lamb D.S.
        • Greig L.
        • Russell G.L.
        • et al.
        Patterns of failure after iodine-125 seed implantation for prostate cancer.
        Radiother Oncol. 2014; 112: 68-71
        • Lo A.C.
        • Morris W.J.
        • Pickles T.
        • et al.
        Patterns of recurrence after low-dose-rate prostate brachytherapy: a population-based study of 2223 consecutive low- and intermediate-risk patients.
        Int J Radiat Oncol Biol Phys. 2015; 91: 745-751
        • Morris M.J.
        • Rowe S.P.
        • Gorin M.A.
        • et al.
        Diagnostic performance of 18F-DCFPyL-PET/CT in men with biochemically recurrent prostate cancer: results from the CONDOR phase III, multicenter study.
        Clin Cancer Res. 2021; 27: 3674-3682
        • Pienta K.J.
        • Gorin M.A.
        • Rowe S.P.
        • et al.
        A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with 18F-DCFPyL in prostate cancer patients (OSPREY).
        J Urol. 2021; 206: 52-61
        • Lamb D.S.
        • Greig L.
        • FitzJohn T.
        • et al.
        Relapse patterns after low-dose-rate prostate brachytherapy.
        Brachytherapy. 2021; 20: 291-295
        • Rousseau E.
        • Raman S.
        • Keyes M.
        • et al.
        Patterns of prostate cancer recurrence after brachytherapy imaged with PSMA-targeting 18F-DCFPyL PET/CT.
        Int J Radiat Oncol Biol Phys. 2019; 105 (, Supplement): E304-E305
        • Mena E.
        • Lindenberg M.L.
        • Turkbey I.B.
        • et al.
        18F-DCFPyL PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy.
        J Nucl Med. 2020; 61: 881-889
        • Wondergem M.
        • Jansen B.H.E.
        • van der Zant F.M.
        • et al.
        Early lesion detection with 18F-DCFPyL PET/CT in 248 patients with biochemically recurrent prostate cancer.
        Eur J Nucl Med Mol Imaging. 2019; 46: 1911-1918
        • Sprute K.
        • Kramer V.
        • Koerber S.A.
        • et al.
        Diagnostic accuracy of 18F-PSMA-1007 PET/CT imaging for lymph node staging of prostate carcinoma in primary and biochemical recurrence.
        J Nucl Med. 2021; 62: 208-213
        • Liu W.
        • Zukotynski K.
        • Emmett L.
        • et al.
        A Prospective study of 18F-DCFPyL PSMA PET/CT restaging in recurrent prostate cancer following primary external beam radiotherapy or brachytherapy.
        Int J Radiat Oncol Biol Phys. 2020; 106: 546-555
        • Joshi A.
        • Roberts M.J.
        • Perera M.
        • et al.
        The clinical efficacy of PSMA PET/MRI in biochemically recurrent prostate cancer compared with standard of care imaging modalities and confirmatory histopathology: results of a single-centre, prospective clinical trial.
        Clin Exp Metastasis. 2020; 37: 551-560
        • Raveenthiran S.
        • Yaxley J.
        • Gianduzzo T.
        • et al.
        The use of 68Ga-PET/CT PSMA to determine patterns of disease for biochemically recurrent prostate cancer following primary radiotherapy.
        Prostate Cancer Prostatic Dis. 2019; 22: 385-390
        • Valle L.F.
        • Greer M.D.
        • Shih J.H.
        • et al.
        Multiparametric MRI for the detection of local recurrence of prostate cancer in the setting of biochemical recurrence after low-dose-rate brachytherapy.
        Diagn Interv Radiol. 2018; 24: 46-53
        • Gaur S.
        • Turkbey B.
        Prostate MR imaging for posttreatment evaluation and recurrence.
        Radiol Clin North Am. 2018; 56: 263-275
        • 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
        • Routman D.
        • Funk R.
        • Stish B.
        • et al.
        Permanent prostate brachytherapy monotherapy with I-125 for low- and intermediate-risk prostate cancer: outcomes in 974 patients.
        Brachytherapy. 2019; 18: 1-7
        • Blacksburg S.R.
        • Stone N.N.
        • Stock R.G.
        Seminal vesicle implantation does not significantly affect prostate cancer treatment-related outcomes.
        Int J Radiat Oncol Biol Phys. 2013; 87: S126
        • Hara T.
        • Inoue Y.
        • Satoh T.
        • et al.
        Diffusion-weighted imaging of local recurrent prostate cancer after radiation therapy: comparison with 22-core three-dimensional prostate mapping biopsy.
        Magn Reson Imaging. 2012; 30: 1091-1098
        • Kim C.K.
        • Park B.K.
        • Park W.
        • Kim S.S.
        Prostate MR imaging at 3T using a phased-arrayed coil in predicting locally recurrent prostate cancer after radiation therapy: preliminary experience.
        Abdom Imaging. 2010; 35: 246-252
        • Kim C.K.
        • Park B.K.
        • Lee H.M.
        Prediction of locally recurrent prostate cancer after radiation therapy: incremental value of 3T diffusion-weighted MRI.
        J Magn Reson Imaging. 2009; 29: 391-397
        • Nag S.
        • Bice W.
        • DeWyngaert K.
        • et al.
        The American Brachytherapy Society recommendations for permanent prostate brachytherapy postimplant dosimetric analysis.
        Int J Radiat Oncol Biol Phys. 2000; 46: 221-230