title: Are all grade group 4 prostate cancers created equal? Implications for the applicability of the novel grade grouping.
abstract: According to the novel prostate cancer (PCa) grade grouping, men with Gleason score 8 should be included in the grade group 4 regardless of primary and secondary scores. We aimed at evaluating the effect of Gleason patterns on the risk of recurrence in men with grade group 4 PCa.
  
  
  
  Overall, 1,089 patients treated with radical prostatectomy with grade group 4 PCa at final pathology were identified. Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen values≥0.2ng/ml and rising. Clinical recurrence (CR) was defined as positive imaging after BCR. Kaplan-Meier analyses assessed time to BCR and CR. Multivariable Cox regression analyses assessed the impact of Gleason patterns on the risk of BCR and CR.
  
  
  
  Overall, 295 (27.1%), 651 (59.8%), and 143 (13.1%) patients had pathologic Gleason pattern 3+5, 4+4, and 5+3. Overall, 435 (39.9%) patients had positive margins and 439 (30.2%), 300 (27.5%), 350 (32.1%), and 216 (19.8%) had pT2, pT3a, pT3b/4, and pN1 disease. Median follow-up was 83 months. Overall, 536 and 221 patients experienced BCR and CR. The 10-year BCR- and CR-free survival rates were 42.9% and 67.5% vs. 38.3% and 59.7% vs. 40.6% and 50.4% for patients with pathologic Gleason pattern 3+5 vs. 4+4 vs. 5+3, respectively (all P≤0.005). In multivariable analyses, patients with Gleason pattern 3+5 were at lower risk of BCR compared to those with 4+4 (P = 0.002). Men with Gleason pattern 3+5 were at lower risk of CR compared to those with 4+4 and 5+3 (all P≤ 0.01).
  
  
  
  Patients with a primary Gleason score 3 are at reduced risk of recurrence as compared to their counterparts with 4 or 5. Primary and secondary Gleason scores should be considered to stratify the risk of recurrence after surgery in patients with grade group 4 PCa.
authors.affiliation: Unit of Urology, Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: giorgio.gandaglia@gmail.com.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gandaglia
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Urology, L'Institut Mutualiste Montsouris, Paris, France.
authors.forename: Arjun
authors.initials: A
authors.lastname: Sivaraman
authors.affiliation: Unit of Urology, Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Marco
authors.initials: M
authors.lastname: Moschini
authors.affiliation: Unit of Urology, Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Department of Urology, L'Institut Mutualiste Montsouris, Paris, France.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fossati
authors.affiliation: Unit of Urology, Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zaffuto
authors.affiliation: Unit of Urology, Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: DellʼOglio
authors.affiliation: Department of Urology, L'Institut Mutualiste Montsouris, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Cathelineau
authors.affiliation: Unit of Urology, Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Urology, L'Institut Mutualiste Montsouris, Paris, France.
authors.forename: Rafael
authors.initials: R
authors.lastname: Sanchez-Salas
authors.affiliation: Unit of Urology, Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D060787:Neoplasm Grading / Q000379:methods*; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000473:pathology*
keywords: Biochemical recurrence; Gleason score; Novel grade grouping; Prostate cancer; Radical prostatectomy