title: Utility of Gleason pattern 4 morphologies detected on transrectal ultrasound (TRUS)-guided biopsies for prediction of upgrading or upstaging in Gleason score 3 + 4 = 7 prostate cancer.
abstract: Selected patients with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) detected on transrectal ultrasound (TRUS)-guided biopsies may be considered for active surveillance (AS); however, a proportion of these will harbor more aggressive disease. The purpose of this study was to determine if morphologies of Gleason pattern 4 PCa may predict upgrading and/or upstaging after radical prostatectomy (RP). A database search for men with GS 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsy that underwent RP between January 2010 and October 2015 identified 152 patients. Two blinded genitourinary pathologists independently reviewed the biopsies and assessed ill-defined glands (IDG), fused glands, small or large cribriform patterns, and glomerulations. Patient age, serum prostate-specific antigen (PSA), percentage (%) of biopsy sites involved by 3 + 4 = 7 PCa, and overall extent of pattern 4 were also recorded. GS and stage (presence or absence of extraprostatic extension [EPE]) were retrieved from RP reports. Data were compared using independent t tests and chi-square. Inter-observer agreement was calculated using Cohen's Kappa statistic. Percent of biopsy sites and extent of pattern 4 were compared to statistically significant morphologies using the Spearman correlation. 28.3 % (43/152) of patients were upgraded to GS >3 + 4 = 7 at RP (GS 4 + 3 = 7 [N = 17], GS 4 + 3 = 7 with tertiary pattern 5 [N = 25], and GS 4 + 5 = 9 [N = 1]) and 44.1 % (67/152) showed EPE after RP. PSA was associated with both upgrading (8.5 ± 5.4 vs. 6.9 ± 3.2 ng/mL, [p = 0.04]) and EPE (8.2 ± 4.6 vs. 6.7 ± 3.2 ng/mL, [p = 0.03]). IDG, fused glands, and glomerulations were not associated with upgrading or EPE (p > 0.05) with moderate to strong inter-observer agreement (K = 0.76-0.88). There was strong inter-observer agreement for small and large cribriform formations (K = 0.93 and 0.94, respectively) and both patterns were strongly associated with upgrading (p < 0.001) and EPE (p = 0.02) on RP. Strong associations were observed between increasing number of morphologies and both upgrading (p = 0.0.25) and EPE (p < 0.001). Overall extent of pattern 4 was associated with upgrading (p = 0.009) and EPE (p = 0.019) while percent of sites involved by GS 3 + 4 = 7 was only associated with EPE (p = 0.023). Cribriform morphology correlated to percentage of sites with 3 + 4 and overall extent of pattern 4 (rho = 0.25, p = 0.002, rho = 0.20, p = 0.015, respectively). Presence of cribriform morphology on TRUS-guided biopsy is strongly associated with upgrading and upstaging at RP and shows near-perfect inter-observer agreement whereas IDG, fused glands, and glomerulations were not useful. Cribriform morphology may be of importance when considering treatment plans for patients with intermediate risk PCa.
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada. tflood@toh.on.ca.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Flood
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada.|Department of Medical Imaging, The Ottawa Hospital, Ottawa, Canada.
authors.forename: Nicola
authors.initials: N
authors.lastname: Schieda
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada.|Department of Urology, The Ottawa Hospital, Ottawa, Canada.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Keefe
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada.|Department of Urology, The Ottawa Hospital, Ottawa, Canada.
authors.forename: Rodney H
authors.initials: RH
authors.lastname: Breau
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada.|Department of Urology, The Ottawa Hospital, Ottawa, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Morash
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Hogan
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Belanger
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Kien T
authors.initials: KT
authors.lastname: Mai
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Robertson
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D012307:Risk Factors
chemical_list: D017430:Prostate-Specific Antigen
keywords: Active surveillance; Cribriform morphology; Gleason score; Prostate; Prostate cancer; TRUS-guided needle biopsy