title: 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.
abstract: 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
  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.
authors.affiliation: Department of Radiation Oncology, University Hospital Ulm, Germany. Electronic address: thomas.wiegel@uniklinik-ulm.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wiegel
authors.affiliation: Department of Radiation Oncology, University Hospital Ulm, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Bartkowiak
authors.affiliation: Department of Radiation Oncology, University Hospital Ulm, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bottke
authors.affiliation: Department of Radiation Oncology, University Hospital Ulm, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Thamm
authors.affiliation: WiSP, Research Institute Pharma GmbH, Langenfeld, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.affiliation: Department of Urology, University Hospital Homburg/Saar, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stöckle
authors.affiliation: Department of Radiation Oncology, University Hospital Homburg/Saar, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rübe
authors.affiliation: Department of Urology, University Hospital Münster, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Semjonow
authors.affiliation: Department of Urology, University Hospital Dresden, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Wirth
authors.affiliation: Department of Pathology, HELIOS Hospital Wuppertal, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Störkel
authors.affiliation: Department of Pathology, HELIOS Hospital Wuppertal, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Golz
authors.affiliation: Department of Radiation Oncology, University Hospital Giessen-Marburg, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Engenhart-Cabillic
authors.affiliation: Department of Urology, University Hospital Giessen-Marburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Hofmann
authors.affiliation: Department of Radiation Oncology, General Hospital Fulda, Germany.
authors.forename: Horst-Jürgen
authors.initials: HJ
authors.lastname: Feldmann
authors.affiliation: Department of Urology, General Hospital Fulda, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Kälble
authors.affiliation: Department of Radiation Oncology, University Hospital Berlin, Germany.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Siegmann
authors.affiliation: Department of Radiation Oncology, University Hospital Berlin, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hinkelbein
authors.affiliation: Department of Urology, University Hospital Berlin, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Steiner
authors.affiliation: Department of Urology, University Hospital Berlin, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000517:prevention & control*; D015995:Prevalence; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000401:mortality* / Q000706:statistics & numerical data; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000601:surgery*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen