title: Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy.
abstract: BACKGROUND
  The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT).
  
  
  METHODS
  This was a single-institution retrospective analysis from 1987 to 2009 of 13,427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n = 415), antiandrogen therapy alone (n = 400) and combined treatment (n = 333). Kaplan-Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse.
  
  
  RESULTS
  Median duration of NHT was 3 months (interquartile range (IQR) 2-4) whereas median follow-up after RP was 8.3 years (IQR 5-10.8). NHT patients were more likely to be D'Amico high risk, have locally advanced pathologic T stage (≥ pT3), pathologic Gleason scores (GS) of 8-10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P ≤ 0.001 for all). GS could not be assigned to only 3% of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P = 0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P < 0.0001).
  
  
  CONCLUSIONS
  Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Stewart
authors.affiliation: Department of Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Cheville
authors.affiliation: Department of Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Sebo
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: I
authors.initials: I
authors.lastname: Frank
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Boorjian
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Thompson
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Gettman
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Tollefson
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Umbriet
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Psutka
authors.affiliation: Department of Biostatistics, Mayo Clinic, Rochester, MN, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Bergstralh
authors.affiliation: Department of Biostatistics, Mayo Clinic, Rochester, MN, USA.
authors.forename: L
authors.initials: L
authors.lastname: Rangel
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Karnes
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D012189:Retrospective Studies
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal