Radical dose escalation by high-dose-rate brachytherapy for localized prostate cancer—Significance of prostate-specific antigen nadir level within 18 months as correlation for long-term biochemical control

Published:October 25, 2018DOI:



      High-dose-rate brachytherapy (HDR-BT) for dose escalation in localized prostate cancer has been established as one standard treatment option. However, long-term results at followup (FU) ≥5 years are usually needed to ensure robustness of reported outcomes. Potential benefit of salvage therapy is, nevertheless, higher when relapse is diagnosed early. This study aimed to solve this dilemma by evaluating the prostate-specific antigen (PSA) nadir for early prediction of long-term biochemical control.

      Methods and Materials

      Combined pelvis-external beam radiation/HDR-BT boost to EQD2 >100 Gy (α/β = 3) was performed in 459 consecutively treated patients. These patients with an FU ≥ 24 months were analyzed and stratified in PSA nadir (nPSA)-groups by PSA nadir within 18 months after radiotherapy (nPSA18). Kaplan–Meier/log-rank tests and Cox-regression models were used to compare the study endpoints.


      The mean FU was 77 months. A PSA nadir within 18 months (nPSA18) <0.5 ng/mL was achieved in 222 patients with median time to reach nPSA18 of 7 months. The 5-year American Society of Therapeutic Radiology and Oncology (ASTRO) biochemical control (prostate-specific antigen disease-free survival) for the nPSA18 group <0.5 ng/mL was 89% and for the group ≥ 0.5 ng/mL, it was 78.6% (p = 0.011). nPSA18 was an independent predictor of cancer-specific survival, distant metastasis-free survival, and biochemical control (ASTRO) (p = 0.026, p = 0.020, and p = 0.01, respectively).


      The present results suggest that the PSA nadir level within 18 months after radiotherapy may serve as an early parameter for long-term biochemical control according to ASTRO definitions following radical dose escalation by HDR-BT for prostate cancer. Excellent outcomes were associated with nPSA18 < 0.5 ng/mL.


      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


        • Blasko J.C.
        • Mate T.
        • Sylvester J.E.
        • et al.
        Brachytherapy for carcinoma of the prostate: Techniques, patient selection, and clinical outcomes.
        Semin Radiat Oncol. 2002; 12: 81-94
        • Sylvester J.E.
        • Grimm P.D.
        • Wong J.
        • et al.
        Fifteen-year biochemical relapse-free survival, cause-specific survival, and overall survival following I (125) prostate brachytherapy in clinically localized prostate cancer: seattle experience.
        Int J Radiat Oncol Biol Phys. 2011; 81: 376-381
        • Ishiyama H.
        • Kamitani N.
        • Kawamura H.
        • et al.
        Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT consortium.
        Brachytherapy. 2017; 16: 503-510
        • Galalae R.M.
        • Zakikhany N.H.
        • Geiger F.
        • et al.
        The 15-year outcomes of high-dose-rate brachytherapy for radical dose escalation in patients with prostate cancer - a benchmark for high-tech external beam radiotherapy alone?.
        Brachytherapy. 2014; 13: 117-122
        • 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
        • Oesterling J.E.
        Prostate specific antigen: A critical assessment of the most useful tumor marker for adenocarcinoma of the prostate.
        J Urol. 1991; 145: 907-923
      1. Consensus statement: guidelines for PSA following radiation therapy. American society for therapeutic radiology and oncology consensus panel.
        Int J Radiat Oncol Biol Phys. 1997; 37: 1035-1041
        • Roach M.
        • Hanks G.
        • Thames 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
        • Aref I.
        • Eapen L.
        • Agboola O.
        • et al.
        The relationship between biochemical failure and time to nadir in patients treated with external beam therapy for T1-T3 prostate carcinoma.
        Radiother Oncol. 1998; 48: 203-207
        • Cavanaugh S.X.
        • Kupelian P.A.
        • Fuller C.D.
        • et al.
        Early prostate-specific antigen (PSA) kinetics following prostate carcinoma radiotherapy: Prognostic value of a time-and-PSA threshold model.
        Cancer. 2004; 101: 96-105
        • Crook J.M.
        • Bahadur Y.A.
        • Bociek R.G.
        • et al.
        Radiotherapy for localized prostate carcinoma. The correlation of pretreatment prostate specific antigen and nadir prostate specific antigen with outcome as assessed by systematic biopsy and serum prostate specific antigen.
        Cancer. 1997; 79: 328-336
        • Crook J.M.
        • Choan E.
        • Perry G.A.
        • et al.
        Serum prostate-specific antigen profile following radiotherapy for prostate cancer: Implications for patterns of failure and definition of cure.
        Urology. 1998; 51: 566-572
        • Zelefsky M.J.
        • Fuks Z.
        • Hunt M.
        • et al.
        High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer.
        J Urol. 2001; 166: 876-881
        • 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
        • 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
        • 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 randomised controlled trial.
        Lancet Oncol. 2014; 15: 464-473
        • Rosser C.J.
        • Kuban D.A.
        • Levy L.B.
        • et al.
        Prostate specific antigen bounce phenomenon after external beam radiation for clinically localized prostate cancer.
        J Urol. 2002; 168: 2001-2005
        • Ray M.E.
        • Thames H.D.
        • Levy L.B.
        • et al.
        PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: A multi-institutional analysis.
        Int J Radiat Oncol Biol Phys. 2006; 64: 1140-1150
        • Hanlon A.L.
        • Diratzouian H.
        • Hanks G.E.
        Posttreatment prostate-specific antigen nadir highly predictive of distant failure and death from prostate cancer.
        Int J Radiat Oncol Biol Phys. 2002; 53: 297-303
        • Tseng Y.D.
        • Chen M.H.
        • Beard C.J.
        • et al.
        Posttreatment prostate specific antigen nadir predicts prostate cancer specific and all cause mortality.
        J Urol. 2012; 187: 2068-2073
        • Zelefsky M.J.
        • Shi W.
        • Yamada Y.
        • et al.
        Postradiotherapy 2-year prostate-specific antigen nadir as a predictor of long-term prostate cancer mortality.
        Int J Radiat Oncol Biol Phys. 2009; 75: 1350-1356
        • Sterzing F.
        • Kratochwil C.
        • Fiedler H.
        • et al.
        (68)Ga-PSMA-11 PET/CT: a new technique with high potential for the radiotherapeutic management of prostate cancer patients.
        Eur J Nucl Med Mol Imaging. 2016; 43: 34-41
        • Stephenson A.J.
        • Scardino P.T.
        • Kattan M.W.
        • et al.
        Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy.
        J Clin Oncol. 2007; 25: 2035-2041
        • 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
        • Chen C.P.
        • Weinberg V.
        • Shinohara K.
        • et al.
        Salvage HDR brachytherapy for recurrent prostate cancer after previous definitive radiation therapy: 5-year outcomes.
        Int J Radiat Oncol Biol Phys. 2013; 86: 324-329
        • Jiang P.
        • van der Horst C.
        • Kimmig B.
        • et al.
        Interstitial high-dose-rate brachytherapy as salvage treatment for locally recurrent prostate cancer after definitive radiation therapy: Toxicity and 5-year outcome.
        Brachytherapy. 2017; 16: 186-192
        • Kollmeier M.A.
        • McBride S.
        • Taggar A.
        • et al.
        Salvage brachytherapy for recurrent prostate cancer after definitive radiation therapy: A comparison of low-dose-rate and high-dose-rate brachytherapy and the importance of prostate-specific antigen doubling time.
        Brachytherapy. 2017; 16: 1091-1098
        • Strom T.J.
        • Wilder R.B.
        • Fernandez D.C.
        • et al.
        High-dose-rate brachytherapy with or without intensity modulated radiation therapy as salvage treatment for an isolated, gross local recurrence of prostate cancer post-prostatectomy.
        Brachytherapy. 2014; 13: 123-127