title: Clinical Validation of the 2005 ISUP Gleason Grading System in a Cohort of Intermediate and High Risk Men Undergoing Radical Prostatectomy.
abstract: In 2005, the International Society of Urological Pathology (ISUP) introduced several modifications to the original Gleason system that were intended to enhance the prognostic power of Gleason score (GS). The objective of this study was to clinically validate the 2005 ISUP Gleason grading system for its ability to detect metastasis. We queried our institutional RP database for men with NCCN clinically localized intermediate to high-risk disease undergoing radical prostatectomy (RP) between 1992 and 2010 with no additional treatment until the time of metastatic progression. A case-cohort design was utilized. A total of 333 available RP samples were re-reviewed and GS was reassigned per the 2005 ISUP Gleason system. Cumulative incidence of metastasis was 0%, 8.4%, 24.5% and 44.4% among specimens that were downgraded, unchanged, had one point GS increase and two point GS increase, respectively. The hazard ratio for metastasis raised in GS 8 and 9 compared to GS 7 from 2.77 and 5.91 to 3.49 and 9.31, respectively. The survival c-index of GS increased from 0.70 to 0.80 when samples were re-graded at 5 years post RP. The c-index of the reassigned GS was higher than the original GS (0.77 vs 0.64) for predicting PCSM at 10 years post RP. The regraded GS improved the prediction of metastasis and PCSM. This validates the updated Gleason grading system using an unambiguous clinical endpoint and highlights the need for reassignment of Gleason grading according to 2005 ISUP system when considering comparisons of novel biomarkers to clinicopathological variables in archival cohorts.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Sheila F
authors.initials: SF
authors.lastname: Faraj
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Stephania M
authors.initials: SM
authors.lastname: Bezerra
authors.affiliation: GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors.forename: Kasra
authors.initials: K
authors.lastname: Yousefi
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Helen
authors.initials: H
authors.lastname: Fedor
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Glavaris
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Misop
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Humphreys
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Tosoian
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Johnson
authors.affiliation: GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Trock
authors.affiliation: Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schaeffer
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Ross
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000601:surgery*; D000328:Adult; D000368:Aged; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011467:Prostate / Q000473:pathology; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery*; D012307:Risk Factors