title: Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.
abstract: Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP.
  
  
  
  A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction.
  
  
  
  Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP.
  
  
  
  Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa.
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kozminski
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Scott
authors.initials: S
authors.lastname: Tomlins
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Adam
authors.initials: A
authors.lastname: Cole
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Udit
authors.initials: U
authors.lastname: Singhal
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Louis
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI; VA HSR&D Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI.
authors.forename: Ted A
authors.initials: TA
authors.lastname: Skolarus
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Palapattu
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Montgomery
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Alon Z
authors.initials: AZ
authors.lastname: Weizer
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Brent K
authors.initials: BK
authors.lastname: Hollenbeck
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: David C
authors.initials: DC
authors.lastname: Miller
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Chang
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: Department of Urology, University of Michigan Medical School, Ann Arbor, MI. Electronic address: tomorgan@med.umich.edu.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Morgan
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery*
chemical_list: D017430:Prostate-Specific Antigen
keywords: Biochemical recurrence; Biomarkers; Prostate cancer