title: Cribriform morphology predicts upstaging after radical prostatectomy in patients with Gleason score 3 + 4 = 7 prostate cancer at transrectal ultrasound (TRUS)-guided needle biopsy.
abstract: Selected patients with transrectal ultrasound (TRUS)-guided biopsies containing Gleason score 3 + 4 = 7 prostate cancer (PCa) may be considered candidates for active surveillance (AS). The purpose of this study was to determine if there are features that predict PCa upstaging and/or upgrading after radical prostatectomy (RP) in patients with Gleason score 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsies. We searched our institution's database for patients with Gleason score 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsy who underwent subsequent RP between January 2010 and January 2015. Two blinded genitourinary pathologists independently reviewed and assessed the following on biopsies: (a) nuclear size, nucleolar size and distribution of macronucleoli of PCa, which were subjectively graded using a semi-quantitative scale from 1 to 3, and (b) PCa with cribriform morphology and the size of cribriform disease. Patient age, serum prostate-specific antigen (PSA) and PSA density (PSAD) were also recorded. The Gleason score and stage (presence or absence of organ-confined disease (OCD)) were retrieved from RP reports. Comparisons were performed between groups using the chi-square test and Spearman correlation. One hundred and four patients were identified to have met inclusion criteria. The mean age was 63 (±6.1) years. Mean PSA and PSAD at diagnosis were 7.5 (±4.2) and 0.25 (±0.15) ng/mL, respectively. Gleason scores were upgraded to greater than 3 + 4 = 7 in 26.9 % (28/104) of patients, and 44.2 % (46/104) of patients had no OCD after RP. There was no correlation between age, PSA, PSAD or percent of biopsies with Gleason pattern 4 for either Gleason score upgrading or absence of OCD at the time of RP (p > 0.05). Thirty patients had cribriform morphology on TRUS-guided biopsy of which 60 % (18/30) had no OCD at RP (p = 0.04) while 36.7 % (11/30) were upgraded to Gleason score ≥3 + 4 = 7 after RP (p = 0.15). There was no association between nuclear size, nucleolar size and/or distribution of macronucleoli with upgrading and/or absence of OCD (p > 0.05). The size of cribriform pattern was not associated with the absence of OCD (p = 0.43) or Gleason score upgrade (p = 0.28). A proportion of patients with Gleason score 3 + 4 = 7 PCa at needle biopsy do not have OCD or are upgraded to higher Gleason scores after RP. In our study, patients with Gleason score 3 + 4 = 7 PCa with the presence of cribriform pattern 4 had a significantly increased chance of being found to have no OCD at the time of RP. There were no clinical or pathologic parameters at the time of TRUS-guided biopsy that identified risk factors for Gleason score upgrading at RP in this study. Cribriform morphology detected on biopsy in patients with Gleason score 3 + 4 = 7 PCa is associated with tumour upstaging after RP and may be considered a contraindication to active surveillance.
authors.affiliation: The Ottawa Hospital, Department of Urology, The University of Ottawa, Ottawa, Canada.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Keefe
authors.affiliation: The Ottawa Hospital, Department of Medical Imaging, The University of Ottawa, Ottawa, Canada.
authors.forename: Nicola
authors.initials: N
authors.lastname: Schieda
authors.affiliation: The Ottawa Hospital, Department of Pathology and Laboratory Medicine, The University of Ottawa, Ottawa, Canada.
authors.forename: Soufiane
authors.initials: S
authors.lastname: El Hallani
authors.affiliation: The Ottawa Hospital, Department of Urology, The University of Ottawa, Ottawa, Canada.
authors.forename: Rodney H
authors.initials: RH
authors.lastname: Breau
authors.affiliation: The Ottawa Hospital, Department of Urology, The University of Ottawa, Ottawa, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Morash
authors.affiliation: The Ottawa Hospital, Department of Pathology and Laboratory Medicine, The University of Ottawa, Ottawa, Canada.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Robertson
authors.affiliation: The Ottawa Hospital, Department of Pathology and Laboratory Medicine, The University of Ottawa, Ottawa, Canada.
authors.forename: Kien T
authors.initials: KT
authors.lastname: Mai
authors.affiliation: The Ottawa Hospital, Department of Pathology and Laboratory Medicine, The University of Ottawa, Ottawa, Canada.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Belanger
authors.affiliation: The Ottawa Hospital, Department of Pathology and Laboratory Medicine, The University of Ottawa, Ottawa, Canada. tflood@toh.on.ca.|The Ottawa Hospital, Department of Pathology and Laboratory Medicine, Faculty of Medicine, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Room 4278, Ottawa, ON, K1H 8L6, Canada. tflood@toh.on.ca.
authors.forename: Trevor A
authors.identifier: http://orcid.org/0000-0002-5227-2708
authors.initials: TA
authors.lastname: Flood
mesh_terms: D000368:Aged; D001707:Biopsy, Needle / Q000379:methods*; D006801:Humans; D061705:Image-Guided Biopsy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery; D012007:Rectum; D018084:Ultrasonography, Interventional
keywords: Active surveillance; Prostate; Prostate cancer; TRUS-guided needle biopsy