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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:https://doi.org/10.1016/j.ijrobp.2014.09.039

      Objective

      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.

      Results

      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.

      Conclusions

      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.
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      References

        • 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

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