title: The potential impact of reproducibility of Gleason grading in men with early stage prostate cancer managed by active surveillance: a multi-institutional study.
abstract: OBJECTIVE
  We evaluated the reproducibility of Gleason grading as relevant to the clinical treatment of men on active surveillance.
  
  
  METHODS
  Three sets of digital images of prostatic adenocarcinoma in biopsies were reviewed and assigned Gleason scores by a total of 11 pathologists from 7 institutions. Interobserver and intra-observer reproducibility were assessed for assignment of the highest Gleason pattern (3 vs 4 or higher). We also identified 97 consecutive patients on active surveillance. Prostate biopsy glass slides from 82 of the patients were available for re-review and the frequency of carcinoma requiring the distinction of tangentially sectioned Gleason pattern 3 from 4 was determined.
  
  
  RESULTS
  Interobserver reproducibility for classic Gleason patterns was substantial (Light's κ 0.76). Interobserver reproducibility for the histological distinction of tangentially sectioned Gleason pattern 3 from Gleason pattern 4 was only fair (Light's κ 0.27). Intra-observer reproducibility ranged from 65% to 100% (mean 81.5%). Of the 82 patients on active surveillance 61 had carcinoma and 15 (24.5%) had a set of biopsies with at least 1 focus in which the distinction between tangentially sectioned Gleason pattern 3 and poorly formed pattern 4 glands had to be considered.
  
  
  CONCLUSIONS
  The reproducibility of grading classic Gleason patterns is high. However, variability in grading occurred when distinguishing between tangentially sectioned pattern 3 glands and the poorly formed gland subset of pattern 4. Developing universally accepted histological and/or molecular criteria to distinguish these patterns and subsequently characterizing their natural history would be useful when treating patients on active surveillance.
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA. jmck@stanford.edu
authors.forename: Jesse K
authors.initials: JK
authors.lastname: McKenney
authors.forename: Jeff
authors.initials: J
authors.lastname: Simko
authors.forename: Michael
authors.initials: M
authors.lastname: Bonham
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: True
authors.forename: Dean
authors.initials: D
authors.lastname: Troyer
authors.forename: Sarah
authors.initials: S
authors.lastname: Hawley
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Newcomb
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Kunju
authors.forename: Marlo M
authors.initials: MM
authors.lastname: Nicolas
authors.forename: Funda
authors.initials: F
authors.lastname: Vakar-Lopez
authors.forename: Xiaotun
authors.initials: X
authors.lastname: Zhang
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
authors.forename: James D
authors.initials: JD
authors.lastname: Brooks
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy; D001707:Biopsy, Needle / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D015588:Observer Variation; D011159:Population Surveillance; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy; D015203:Reproducibility of Results