title: The New Prostate Cancer Grading System Does Not Improve Prediction of Clinical Recurrence After Radical Prostatectomy: Results of a Large, Two-Center Validation Study.
abstract: A new prostate cancer (PCa) grading system (namely, Gleason score-GS- ≤6 vs. 3 + 4 vs. 4 + 3 vs. 8 vs. ≥9) was recently proposed and assessed on biochemical recurrence (BCR) showing improved predictive abilities compared to the commonly used three-tier system (GS ≤6 vs. 7 vs. ≥8). We assessed the predictive ability of the five-tier grade group (GG) system on harder clinical endpoint, namely clinical recurrence (CR).
  
  
  
  Between 2005 and 2014, 9,728 clinically localized PCa patients were treated with radical prostatectomy (RP) at two tertiary referral centers. Kaplan-Meier curves, multivariable Cox regression analyses, and concordance index (C-index) were used to assess CR after treatment according to four Gleason grade classifications at biopsy and RP: Group 1: ≤6 versus 7 versus ≥8; Group 2: ≤6 versus 3 + 4 vs. 4 + 3 versus ≥8; Group 3: ≤6 versus 7 versus 8 versus ≥9; Group 4: ≤6 versus 3 + 4 versus 4 + 3 versus 8 versus ≥9. Same analyses were repeated in patients who had BCR (n = 1,624). Decision curve analyses were performed to evaluate and compare the net benefit associated with the use of the four Gleason grade classifications.
  
  
  
  Overall, 443 (4.6%) patients had CR. The hazard ratio of the GS 3 + 4, 4 + 3, 8, and ≥9 relative to GS ≤6 were 3.63, 5.93, 11.44, 18.08 and 4.93, 9.99, 15.31 and 25.12 in the pre- and post-treatment models, respectively. The C-index of the five-tier GG system was slightly higher relative to the other 3 Gleason grade classifications both in the pre- (range: 0.001-0.006) and post-treatment models (range: 0-0.008). Similar findings were observed when we focused our analyses in patients with BCR after RP. The use of the five-tier GG system did not result into higher net-benefit relative to the other three Gleason grade classifications.
  
  
  
  The difference in accuracy between the five-tier GG system and the other Gleason grade classifications, using CR as an endpoint, is clinically negligible. Current evidence suggests that the five-tier GG system represents a simplified user-friendly scheme available for patient counseling rather than a new histopathological diagnostic system that improves the prediction of CR. Prostate 77:263-273, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada.
authors.forename: Paolo
authors.initials: P
authors.lastname: Dell'Oglio
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Robert Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gandaglia
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fossati
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Stabile
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Department of Urology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Marco
authors.initials: M
authors.lastname: Moschini
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Cucchiara
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zaffuto
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nazareno
authors.initials: N
authors.lastname: Suardi
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
mesh_terms: D000368:Aged; D000066491:Clinical Decision-Making / Q000379:methods*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000601:surgery*; D011237:Predictive Value of Tests; D011468:Prostatectomy / Q000401:mortality* / Q000639:trends; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality* / Q000601:surgery; D015996:Survival Rate / Q000639:trends
keywords: Epstein; Gleason grade; clinical recurrence; prostate cancer; validation