title: Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy.
abstract: Invasive cribriform and intraductal carcinoma in radical prostatectomy specimens have been associated with an adverse clinical outcome. Our objective was to determine the prognostic value of invasive cribriform and intraductal carcinoma in pre-treatment biopsies on time to disease-specific death. We pathologically revised the diagnostic biopsies of 1031 patients from the first screening round of the European Randomized Study of Screening for Prostate Cancer (1993-2000). Ninety percent of all patients (n=923) had received active treatment, whereas 10% (n=108) had been followed by watchful waiting. The median follow-up was 13 years. Patients who either had invasive cribriform growth pattern or intraductal carcinoma were categorized as CR/IDC+. The outcome was disease-specific survival. Relationships with outcome were analyzed using multivariable Cox regression and log-rank analysis. In total, 486 patients had Gleason score 6 (47%) and 545 had ≥7 (53%). The 15-year disease-specific-survival probabilities were 99% in Gleason score 6 (n=486), 94% in CR/IDC- Gleason score ≥7 (n=356) and 67% in CR/IDC+ Gleason score ≥7 (n=189). CR/IDC- Gleason score 3+4=7 patients did not have statistically different survival probabilities from those with Gleason score 6 (P=0.30), while CR/IDC+ Gleason score 3+4=7 patients did (P<0.001). In multivariable analysis, CR/IDC+ status was independently associated with a poorer disease-specific survival (HR 2.6, 95% CI 1.4-4.8, P=0.002). We conclude that CR/IDC+ status in prostate cancer biopsies is associated with a worse disease-specific survival. Our findings indicate that men with biopsy CR/IDC- Gleason score 3+4=7 prostate cancer could be candidates for active surveillance, as these patients have similar survival probabilities to those with Gleason score 6.
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Kweldam
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Intan P
authors.initials: IP
authors.lastname: Kümmerlin
authors.affiliation: Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: Nieboer
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Esther I
authors.initials: EI
authors.lastname: Verhoef
authors.affiliation: Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.affiliation: Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
authors.forename: Theodorus H
authors.initials: TH
authors.lastname: van der Kwast
authors.affiliation: Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Geert J
authors.initials: GJ
authors.lastname: van Leenders
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D000368:Aged; D001706:Biopsy; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005060:Europe; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome