Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

Published:November 20, 2014DOI:


      The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C).

      Methods and Materials

      For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method.


      Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression.


      A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups will benefit most from which treatment option.
      To read this article in full you will need to make a payment
      ASTRO Member Login
      ASTRO Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.
      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'

      Purchase one-time access:

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


        • Bianco Jr., F.J.
        • Scardino P.T.
        • Eastham J.A.
        Radical prostatectomy: Long-term cancer control and recovery of sexual and urinary function (“trifecta”).
        Urology. 2005; 66: 83-94
        • Walsh P.C.
        • Partin A.W.
        • Epstein J.I.
        Cancer control and quality of life following anatomical radical retropubic prostatectomy: Results at 10 years.
        J Urol. 1994; 152: 1831-1836
        • Kawamorita N.
        • Saito S.
        • Ishidoya S.
        • et al.
        Radical prostatectomy for high-risk prostate cancer: Biochemical outcome.
        Int J Urol. 2009; 16: 733-738
        • Bolla M.
        • van Poppel H.
        • Tombal B.
        • et al.
        Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: Long-term results of a randomised controlled trial (EORTC trial 22911).
        Lancet. 2012; 380: 2018-2027
        • Thompson I.M.
        • Tangen C.M.
        • Paradelo J.
        • et al.
        Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: Long-term followup of a randomized clinical trial.
        J Urol. 2009; 181: 956-962
        • Wiegel T.
        • Bartkowiak D.
        • Bottke D.
        • et al.
        Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96–02/AUO AP 09/95 trial.
        Eur Urol. 2014; 66: 243-250
        • Bottke D.
        • Bartkowiak D.
        • Schrader M.
        • et al.
        Radiotherapy after radical prostatectomy: Immediate or early delayed?.
        Strahlenther Onkol. 2012; 188: 1096-1101
        • Briganti A.
        • Wiegel T.
        • Joniau S.
        • et al.
        Early salvage radiation therapy does not compromise cancer control in patients with pT3N0 prostate cancer after radical prostatectomy: Results of a match-controlled multi-institutional analysis.
        Eur Urol. 2012; 62: 472-487
        • King C.R.
        The timing of salvage radiotherapy after radical prostatectomy: A systematic review.
        Int J Radiat Oncol Biol Phys. 2012; 84: 104-111
        • Hermanek P.
        • Sobin L.H.
        TNM Classification of Malignant Tumours.
        Springer, Berlin, Heidelberg, New York1992
        • Gleason D.F.
        Histological grading and clinical staging of prostatic carcinoma.
        in: Tannenbaum M. Urologic Pathology: The Prostate. Lea & Febiger, Philadelphia1977: 171-198
        • Heidenreich A.
        • Bastian P.J.
        • Bellmunt J.
        • et al.
        EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer.
        Eur Urol. 2014; 65: 467-479
        • Lohm G.
        • Bottke D.
        • Jamil B.
        • et al.
        Salvage radiotherapy in patients with persistently detectable PSA or PSA rising from an undetectable range after radical prostatectomy gives comparable results.
        World J Urol. 2012; 31: 423-428
        • 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
        • Eggener S.E.
        • Scardino P.T.
        • Walsh P.C.
        • et al.
        Predicting 15-year prostate cancer specific mortality after radical prostatectomy.
        J Urol. 2011; 185: 869-875
        • D'Amico A.V.
        • Chen M.H.
        • Roehl K.A.
        • et al.
        Identifying patients at risk for significant versus clinically insignificant postoperative prostate-specific antigen failure.
        J Clin Oncol. 2005; 23: 4975-4979
        • Sengupta S.
        • Christensen C.M.
        • Zincke H.
        • et al.
        Detectable prostate specific antigen between 60 and 120 days following radical prostatectomy for prostate cancer: Natural history and prognostic significance.
        J Urol. 2006; 176: 559-563
        • Eisenberg M.L.
        • Davies B.J.
        • Cooperberg M.R.
        • et al.
        Prognostic implications of an undetectable ultrasensitive prostate-specific antigen level after radical prostatectomy.
        Eur Urol. 2010; 57: 622-629
        • Audenet F.
        • Seringe E.
        • Drouin S.J.
        • et al.
        Persistently elevated prostate-specific antigen at six weeks after radical prostatectomy helps in early identification of patients who are likely to recur.
        World J Urol. 2012; 30: 239-244
        • Kernek K.M.
        • Koch M.O.
        • Daggy J.K.
        • et al.
        The presence of benign prostatic glandular tissue at surgical margins does not predict PSA recurrence.
        J Clin Pathol. 2005; 58: 725-728
        • Katz M.S.
        • Zelefsky M.J.
        • Venkatraman E.S.
        • et al.
        Predictors of biochemical outcome with salvage conformal radiotherapy after radical prostatectomy for prostate cancer.
        J Clin Oncol. 2003; 21: 483-489
        • Johnson S.
        • Jackson W.
        • Li D.
        • et al.
        The interval to biochemical failure is prognostic for metastasis, prostate cancer-specific mortality, and overall mortality after salvage radiation therapy for prostate cancer.
        Int J Radiat Oncol Biol Phys. 2013; 86: 554-561
        • Rogers C.G.
        • Khan M.A.
        • Craig Miller M.
        • et al.
        Natural history of disease progression in patients who fail to achieve an undetectable prostate-specific antigen level after undergoing radical prostatectomy.
        Cancer. 2004; 101: 2549-2556
        • Moreira D.M.
        • Presti Jr., J.C.
        • Aronson W.J.
        • et al.
        Natural history of persistently elevated prostate specific antigen after radical prostatectomy: Results from the SEARCH database.
        J Urol. 2009; 182: 2250-2255
        • Moreira D.M.
        • Banez L.L.
        • Presti Jr., J.C.
        • et al.
        Predictors of secondary treatment following biochemical recurrence after radical prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital database.
        BJU Int. 2010; 105: 28-33
        • Freedland S.J.
        • Humphreys E.B.
        • Mangold L.A.
        • et al.
        Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy.
        JAMA. 2005; 294: 433-439
        • Pound C.R.
        • Partin A.W.
        • Eisenberger M.A.
        • et al.
        Natural history of progression after PSA elevation following radical prostatectomy.
        JAMA. 1999; 281: 1591-1597
        • Swanson G.P.
        • Hussey M.A.
        • Tangen C.M.
        • et al.
        Predominant treatment failure in postprostatectomy patients is local: Analysis of patterns of treatment failure in SWOG 8794.
        J Clin Oncol. 2007; 25: 2225-2229
        • Parker C.
        • Sydes M.R.
        • Catton C.
        • et al.
        Radiotherapy and androgen deprivation in combination after local surgery (RADICALS): A new Medical Research Council/National Cancer Institute of Canada phase III trial of adjuvant treatment after radical prostatectomy.
        BJU Int. 2007; 99: 1376-1379
        • Richaud P.
        • Sargos P.
        • Henriques de Figueiredo B.
        • et al.
        [Postoperative radiotherapy of prostate cancer].
        Cancer Radiother. 2010; 14: 500-503
        • Pearse M.
        • Fraser-Browne C.
        • Davis I.D.
        • et al.
        A Phase III trial to investigate the timing of radiotherapy for prostate cancer with high-risk features: Background and rationale of the Radiotherapy – Adjuvant Versus Early Salvage (RAVES) trial.
        BJU Int. 2014; 113: 7-12
        • Ost P.
        • Lumen N.
        • Goessaert A.S.
        • et al.
        High-dose salvage intensity-modulated radiotherapy with or without androgen deprivation after radical prostatectomy for rising or persisting prostate-specific antigen: 5-year results.
        Eur Urol. 2011; 60: 842-849
        • Gomez P.
        • Manoharan M.
        • Kim S.S.
        • et al.
        Radionuclide bone scintigraphy in patients with biochemical recurrence after radical prostatectomy: When is it indicated?.
        BJU Int. 2004; 94: 299-302
        • Mir M.C.
        • Li J.
        • Klink J.C.
        • et al.
        Optimal definition of biochemical recurrence after radical prostatectomy depends on pathologic risk factors: Identifying candidates for early salvage therapy.
        Eur Urol. 2014; 66: 204-210


      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.