title: Can we expand active surveillance criteria to include biopsy Gleason 3+4 prostate cancer? A multi-institutional study of 2,323 patients.
abstract: OBJECTIVE
  To test the expandability of active surveillance (AS) to Gleason score 3+4 cancers by assessing the unfavorable disease risk in a large multi-institutional cohort.
  
  
  METHODS
  We performed a retrospective analysis including 2,323 patients with localized Gleason score 3+4 prostate cancer who underwent a radical prostatectomy between 2005 and 2013 from 6 academic centers. We analyzed the rates of biopsy downgrading/upgrading and advanced stage in the overall cohort by employing standardized AS criteria (using biopsy Gleason score 3+4).
  
  
  RESULTS
  The final pathologic Gleason score was 3+3 = 6 in 8%, 3+4 = 7 in 67%, 4+3 = 7 in 20%, and 8 to 10 in 5% cases. The overall rate of unfavorable disease (upgrading or advanced stage or both) was 46%. In multivariable analysis, prostate-specific antigen (PSA) level>10 ng/ml, PSA density (PSAD) >0.15 ng/ml/g, clinical stage >T1, and>2 positive cores were predictors of unfavorable disease. According to the AS criteria used, the risk of unfavorable disease ranged from 30% to 42%. In patients without any risk factor (PSA level≤ 10 ng/ml, PSAD ≤ 0.15 ng/ml/g, T1c, and ≤ 2 positive cores), the unfavorable disease rate was 19%. The main limitations of this study are the retrospective design and nonstandardization of pathologic assessment between centers.
  
  
  CONCLUSIONS
  Approximately half of patients with biopsy Gleason score 3+4 cancer have unfavorable disease at final pathology. Nevertheless, expanding AS eligibility to these patients may be acceptable provided adherence to strict selection criteria leading to a<20% risk of unfavorable disease. Future tools for selection such as magnetic resonance imaging, early rebiopsy, and serum markers may be especially beneficial in this group of patients.
authors.affiliation: Department of Urology, Saint-Louis Hospital, Paris, France; Paris 7 University, Paris, France. Electronic address: g.ploussard@gmail.com.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ploussard
authors.affiliation: Prostate Cancer Center Hamburg-Eppendorf, University Hospital Hamburg-Eppendorf and Martini-Clinic, Hamburg, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Isbarn
authors.affiliation: Department of Urology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Sooriakumaran
authors.affiliation: Department of Uronephrology and Renal Transplantation, "Fundeni" Clinical Institute, Bucharest, Romania.
authors.forename: Christian I
authors.initials: CI
authors.lastname: Surcel
authors.affiliation: Department of Urology, Henri Mondor Hospital, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Salomon
authors.affiliation: Department of Pathology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Freschi
authors.affiliation: Department of Uronephrology and Renal Transplantation, "Fundeni" Clinical Institute, Bucharest, Romania.
authors.forename: Cristian
authors.initials: C
authors.lastname: Mirvald
authors.affiliation: The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Henk G
authors.initials: HG
authors.lastname: van der Poel
authors.affiliation: Department of Pathology, Churchill Hospital, Oxford, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Jenkins
authors.affiliation: Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Ost
authors.affiliation: Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Inge M
authors.initials: IM
authors.lastname: van Oort
authors.affiliation: Department of Urology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Yossepowitch
authors.affiliation: Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giannarini
authors.affiliation: University Medical Centre, Utrecht, The Netherlands.
authors.forename: Roderick C N
authors.initials: RC
authors.lastname: van den Bergh
mesh_terms: D000368:Aged; D015331:Cohort Studies; D062665:Epidemiological Monitoring; D006801:Humans; D061705:Image-Guided Biopsy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D012189:Retrospective Studies; D012307:Risk Factors; D018084:Ultrasonography, Interventional
keywords: Active surveillance; Gleason score; Outcomes; Prostate cancer; Radical prostatectomy; Reclassification