title: Heterogeneity in D'Amico classification-based low-risk prostate cancer: Differences in upgrading and upstaging according to active surveillance eligibility.
abstract: BACKGROUND
  To date, no study has examined clinical, pathological, and surgical characteristics of D׳Amico low-risk patients according to active surveillance (AS) eligibility.
  
  
  METHODS
  We relied on patients with low-risk prostate cancer, who were classified based on the D׳Amico classification, treated with radical prostatectomy (RP) between 2008 and 2013 at the Martini-Clinic Prostate Cancer Center. We assessed differences in clinical, pathological, and surgical characteristics in D׳Amico low-risk patients according to AS eligibility (prostate-specific antigen [PSA]≤ 10 ng/ml, Gleason score ≤ 3 + 3, ≤ 2 positive cores,≤5 0% tumor content per core, and ≤ cT1-2a). Multivariable logistic regression analyses targeted 2 end points: (1) presence of either intermediate- or high-risk characteristics (Gleason score ≥ 3+4 or ≥ pT3 or pN1) or (2) exclusive presence of high-risk characteristics (Gleason score ≥ 4+4 or ≥ pT3 or pN1) at RP.
  
  
  RESULTS
  Of 1,331 patients low-risk prostate cancer classified based on the D׳Amico classification, 825 (62%) men were eligible for AS. AS candidates were less frequently either upgraded (55% vs. 78%, P<0.001) or upstaged (8% vs. 15%, P<0.001). Similarly, at final pathology, AS candidates less frequently harbored either intermediate- or high-risk (56% vs. 78%, P<0.001), or exclusive high-risk characteristics (9% vs. 16%, P<0.001). Tumor involvement per core (>50%) (most powerful), number of positive cores, PSA values, and age were independent predictors for either intermediate- or high-risk characteristics at RP. Tumor involvement per core and PSA values were independent predictors for exclusive high-risk characteristics at RP.
  
  
  CONCLUSIONS
  D׳Amico low-risk patients did not have a homogeneous histology at RP. Especially, non-AS candidates were at a higher risk of either upgrading or upstaging at final pathology. Tumor involvement greater than 50% per core was the most powerful indicator of adverse pathology. Therefore, D'Amico low-risk criteria are not safe enough to identify AS candidates.
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada. Electronic address: schiffmann@martini-klinik.de.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schiffmann
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Wenzel
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Salomon
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Budäus
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Wittmer
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kraft
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Krech
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Beyer
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Boehm
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Derya
authors.initials: D
authors.lastname: Tilki
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Michl
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Department of Urology, University of Montreal Health Center, Montreal, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000145:classification* / Q000473:pathology* / Q000601:surgery; D057832:Watchful Waiting
chemical_list: D017430:Prostate-Specific Antigen
keywords: Active surveillance; Low-risk; Prostate cancer; Prostatectomy; Upgrading; Upstaging