title: What is the optimal definition of misclassification in patients with very low-risk prostate cancer eligible for active surveillance? Results from a multi-institutional series.
abstract: BACKGROUND
  The risk of unfavorable prostate cancer in active surveillance (AS) candidates is nonnegligible. However, what represents an adverse pathologic outcome in this setting is unknown. We aimed at assessing the optimal definition of misclassification and its effect on recurrence in AS candidates treated with radical prostatectomy (RP).
  
  
  METHODS
  Overall, 1,710 patients eligible for AS according to Prostate Cancer Research International: Active Surveillance criteria treated with RP between 2000 and 2013 at 3 centers were evaluated. Patients were stratified according to pathology results at RP: organ-confined disease and pathologic Gleason score ≤ 6 (group 1); organ-confined disease and Gleason score 3+4 (group 2); and non-organ-confined disease, Gleason score ≥ 4+3, and nodal invasion (group 3). Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen (PSA) ≥ 0.2 ng/ml. Kaplan-Meier curves assessed time to BCR. Multivariable Cox regression analyses tested the association between pathologic features and BCR. Multivariable logistic regression analyses identified the predictors of adverse pathologic characteristics.
  
  
  RESULTS
  Overall, 926 (54.2%), 653 (33.0%), and 220 (12.9%) patients were categorized in groups 1, 2, and 3, respectively. Median follow-up was 32.2 months. The 5-year BCR-free survival rate was 94.2%. Patients in group 3 had lower BCR-free survival rates compared with those in group 1 (79.1% vs. 97.0%, P<0.001). No differences were observed between patients included in group 1 vs. group 2 (97.0% vs. 94.7%, P = 0.1). These results were confirmed at multivariable analyses and after stratification according to margin status. Older age and PSA density ≥ 10 ng/ml/ml were associated with higher risk of unfavorable pathologic characteristics (i.e., inclusion in group 3; all P<0.001).
  
  
  CONCLUSIONS
  Among patients eligible for AS treated with RP, only men with Gleason score ≥ 4+3 or non-organ-confined disease at final pathology were at increased risk of BCR. These individuals represent the real misclassified AS patients, who can be predicted based on older age and higher PSA density.
authors.affiliation: Unit of Urology/Division of Oncology; URI; IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gandaglia
authors.affiliation: Department of Urology, Saint-Louis Hospital, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ploussard
authors.affiliation: Department of Urology, Regio Clinic Wedel, Wedel, Germany; Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Isbarn
authors.affiliation: Unit of Urology/Division of Oncology; URI; IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Nazareno
authors.initials: N
authors.lastname: Suardi
authors.affiliation: Department of Radiology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Peter J L
authors.initials: PJ
authors.lastname: De Visschere
authors.affiliation: Department of Radiology, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jurgen J
authors.initials: JJ
authors.lastname: Futterer
authors.affiliation: Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Pirus
authors.initials: P
authors.lastname: Ghadjar
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Ost
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Sooriakumaran
authors.affiliation: Centre of Urological Surgery, Dialysis and Renal Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: Christian I
authors.initials: CI
authors.lastname: Surcel
authors.affiliation: Department of Urology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Roderick C N
authors.initials: RC
authors.lastname: van der Bergh
authors.affiliation: Unit of Urology/Division of Oncology; URI; IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
authors.affiliation: Unit of Urology/Division of Oncology; URI; IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giannarini
authors.affiliation: Unit of Urology/Division of Oncology; URI; IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: briganti.alberto@hsr.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000145:classification* / Q000473:pathology* / Q000601:surgery; D012307:Risk Factors; D057832:Watchful Waiting
chemical_list: D017430:Prostate-Specific Antigen
keywords: Active surveillance; Biochemical recurrence; Oncologic outcomes; Prostate cancer; Radical prostatectomy