title: Histologic Grading of Prostatic Adenocarcinoma Can Be Further Optimized: Analysis of the Relative Prognostic Strength of Individual Architectural Patterns in 1275 Patients From the Canary Retrospective Cohort.
abstract: Histologic grading remains the gold standard for prognosis in prostate cancer, and assessment of Gleason score plays a critical role in active surveillance management. We sought to optimize the prognostic stratification of grading and developed a method of recording and studying individual architectural patterns by light microscopic evaluation that is independent of standard Gleason grade. Some of the evaluated patterns are not assessed by current Gleason grading (eg, reactive stromal response). Individual histologic patterns were correlated with recurrence-free survival in a retrospective postradical prostatectomy cohort of 1275 patients represented by the highest-grade foci of carcinoma in tissue microarrays. In univariable analysis, fibromucinous rupture with varied epithelial complexity had a significantly lower relative risk of recurrence-free survival in cases graded as 3+4=7. Cases having focal "poorly formed glands," which could be designated as pattern 3+4=7, had lower risk than cribriform patterns with either small cribriform glands or expansile cribriform growth. In separate multivariable Cox proportional hazard analyses of both Gleason score 3+3=6 and 3+4=7 carcinomas, reactive stromal patterns were associated with worse recurrence-free survival. Decision tree models demonstrate potential regrouping of architectural patterns into categories with similar risk. In summary, we argue that Gleason score assignment by current consensus guidelines are not entirely optimized for clinical use, including active surveillance. Our data suggest that focal poorly formed gland and cribriform patterns, currently classified as Gleason pattern 4, should be in separate prognostic groups, as the latter is associated with worse outcome. Patterns with extravasated mucin are likely overgraded in a subset of cases with more complex epithelial bridges, whereas stromogenic cancers have a worse outcome than conveyed by Gleason grade alone. These findings serve as a foundation to facilitate optimization of histologic grading and strongly support incorporating reactive stroma into routine assessment.
authors.affiliation: *Cleveland Clinic, Cleveland, OH †University of Texas MD Anderson Cancer Center, Houston ††University of Texas Health Sciences Center San Antonio, San Antonio, TX ‡Canary Foundation, Palo Alto #University of California- San Francisco, San Francisco ‡‡Stanford University Medical Center, Stanford, CA §Fred Hutchinson Cancer Research Center ∥University of Washington Medical Center, Seattle, WA **Eastern Virginia Medical School, Norfolk, VA ¶University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jesse K
authors.initials: JK
authors.lastname: McKenney
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Sarah
authors.initials: S
authors.lastname: Hawley
authors.forename: Heidi
authors.initials: H
authors.lastname: Auman
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Newcomb
authors.forename: Hilary D
authors.initials: HD
authors.lastname: Boyer
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.forename: Jeff
authors.initials: J
authors.lastname: Simko
authors.forename: Antonio
authors.initials: A
authors.lastname: Hurtado-Coll
authors.forename: Dean A
authors.initials: DA
authors.lastname: Troyer
authors.forename: Maria S
authors.initials: MS
authors.lastname: Tretiakova
authors.forename: Funda
authors.initials: F
authors.lastname: Vakar-Lopez
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Cooperberg
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Lance
authors.forename: Dan W
authors.initials: DW
authors.lastname: Lin
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: True
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: James D
authors.initials: JD
authors.lastname: Brooks
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000465:Algorithms; D015331:Cohort Studies; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods*; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies; D046888:Tissue Array Analysis