title: Validation of tertiary Gleason pattern 5 in Gleason score 7 prostate cancer as an independent predictor of biochemical recurrence and development of a prognostic model.
abstract: OBJECTIVE
  To validate the biological and prognostic value of tertiary Gleason pattern 5 (TGP5) in patients with Gleason score 7 (GS 7) prostate cancer (PCa) and to develop a prognostic model to identify the high-risk group of patients with TGP5.
  
  
  METHODS
  We retrospectively reviewed the data from 4,146 patients with localized (pT2-3 N0 M0) GS 7 PCa treated by radical prostatectomy (RP) without adjuvant therapy. The primary end point was biochemical recurrence (BCR), and the secondary one was to build a bootstrap-corrected multivariable Cox model.
  
  
  RESULTS
  Of the 4,146 patients, 416 (10%) had a TPG5 in the RP specimen. TGP5 was associated with BCR in both univariable and multivariable analyses that adjusted for the effects of standard pathological features (P<0.001). A prognostic model based on preoperative prostate-specific antigen levels (<10 vs.≥10ng/ml), primary and secondary Gleason pattern (3+4 vs. 4+3), pathological tumor category (pT2/pT3a vs. pT3b), and surgical margin status (R0 vs. R+) stratified patients with a discrimination of 72.2%. Patients in the low-risk group had a 5-year BCR-free survival rate of 76.3% compared with only 18.5% for those in the high-risk group (P<0.001).
  
  
  CONCLUSIONS
  Knowledge of TGP5 improves our prognostication of patients with GS 7 PCa treated with RP. We developed a statistical tool to help identify the patients with TGP5 who are at the highest risk of BCR after RP, thereby helping with the clinical decision making regarding adjuvant trials and follow-up scheduling.
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Department of Urology, Centre hospitalier universitaire vaudois, Lausanne, Switzerland.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lucca
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY. Electronic address: sfshariat@gmail.com.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Urological Research Institute, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Claus G
authors.initials: CG
authors.lastname: Roehrborn
authors.affiliation: Urological Research Institute, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Urology, Landeskrankenhaus Weinviertel-Korneuburg, Korneuburg, Austria.
authors.forename: Mesut
authors.initials: M
authors.lastname: Remzi
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Seitz
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Harun
authors.initials: H
authors.lastname: Fajkovic
authors.affiliation: Department of Urology, Wilhelminenspital, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Klingler
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Québec, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Québec, Canada.
authors.forename: Maxine
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Urology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Faculty of Medicine Pierre et Marie Curie, Institut Universitaire de Cancérologie GRC5, University Paris 6, Paris, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.affiliation: Department of Urology, Krankenhaus der Barmherzigen Schwestern, Linz, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Loidl
authors.affiliation: Department of Urology, Medical University of Graz, Graz, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Pummer
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods / Q000592:standards; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery; D015203:Reproducibility of Results; D012189:Retrospective Studies
keywords: Biochemical recurrence; Gleason 7; Prostate cancer; Risk-stratification model; Tertiary Gleason pattern 5