title: Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer.
abstract: Patients with Gleason score 7 prostate cancer on radical prostatectomy demonstrate a wide range in clinical outcome. Gleason grade 4 prostate cancer encompasses a heterogeneous group of tumor growth patterns including fused, ill-defined, cribriform, and glomeruloid glandular structures. Our objective was to determine the prognostic value of different Gleason grade 4 growth patterns. We performed a nested case-control study among 535 patients with Gleason score 7 prostate cancer at radical prostatectomy, treated between March 1985 and July 2013 at a university hospital in the Netherlands. We analyzed 52 cases (with metastasis, disease-specific mortality or both) and 109 controls, matched for age, PSA level, and pT stage. Presence of the following Gleason grade 4 patterns was recorded: fused, ill-defined, cribriform, and glomeruloid. Intraductal carcinoma of the prostate and tertiary Gleason grade 5 were additionally assessed. Outcomes were metastasis-free survival and disease-specific survival. We used Cox proportional hazards regression to determine the predictive value of Gleason grade 4 patterns for survival time. The overall prevalence of Gleason grade 4 patterns was as follows: fused 75% (n=121), ill-defined 64% (n=102), cribriform 48% (n=83), and glomeruloid 25% (n=40). Cribriform pattern was the only pattern with an unequal distribution between cases and controls. Forty-two out of 52 cases (81%) had cribriform growth pattern versus 41/109 controls (38%). In multivariate analysis, presence of cribriform growth was an adverse independent predictor for distant metastasis-free survival (HR 8.0, 95% CI 3.0-21; P<0.001) and disease-specific survival (HR 5.4, 95% CI 2.0-15, P=0.001). In conclusion, cribriform growth in Gleason grade 4 is a strong prognostic marker for distant metastasis and disease-specific death in patients with Gleason score 7 prostate cancer at radical prostatectomy.
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Kweldam
authors.affiliation: 1] Research Office Sophia, Erasmus Medical Center, Rotterdam, The Netherlands [2] Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Wildhagen
authors.affiliation: Center for Medical Decision Making, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.affiliation: Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.affiliation: Department of Pathology and Laboratory Medicine, University Health Network, Toronto, Canada.
authors.forename: Theodorus H
authors.initials: TH
authors.lastname: van der Kwast
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Geert J L H
authors.initials: GJ
authors.lastname: van Leenders
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000368:Aged; D016022:Case-Control Studies; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology*