title: Is clinical stage T2c prostate cancer an intermediate- or high-risk disease?
abstract: BACKGROUND
  Clinical stage T2c (cT2c) is an indeterminate factor in prostate cancer (PC) risk stratification. According to the D'Amico grouping and American Urological Association guidelines, cT2c is a high risk, whereas the National Comprehensive Cancer Network and the European Urological Association classify cT2c as an intermediate risk. This study assessed whether cT2c tumors without other high-risk factors (clinical stage T2c, not otherwise specified [cT2c-NOS]) behaved as an intermediate or high risk through an analysis of biochemical recurrence (BCR) after radical prostatectomy.
  
  
  METHODS
  Two thousand seven hundred fifty-nine men from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database and 12,900 men from Johns Hopkins Hospital (JHH) from 1988-2011 and 1982-2012, respectively, were analyzed. Patients were grouped into low-risk (prostate-specific antigen [PSA] < 10 ng/mL, Gleason sum ≤ 6, and cT1-T2a), intermediate-risk (PSA = 10-20 ng/mL, Gleason sum = 7, or cT2b), and high-risk PC categories (PSA > 20 ng/mL, Gleason sum = 8-10, or cT3). Men with cT2c tumors who were not otherwise at high risk (ie, PSA< 20 ng/mL and Gleason sum < 8) were placed into a separate category termed cT2c-NOS. Associations between cT2c-NOS and intermediate- and high-risk patients and BCR were tested with the log-rank test and Cox proportional analysis models.
  
  
  RESULTS
  Ninety-nine men (4%) from SEARCH and 202 men (2%) from JHH had tumors classified as cT2c-NOS. The cT2c-NOS patients had a BCR risk similar to that of the intermediate-risk patients (SEARCH, P = .27; JHH, P = .23) but a significantly lower BCR risk in comparison with the high-risk patients (SEARCH, P < .001; JHH, P < .001). When they were specifically compared with intermediate- and high-risk patients, after adjustments for year and center, cT2c-NOS patients had outcomes comparable to those of intermediate-risk patients (SEARCH, P = .53; JHH, P = .54) but significantly better than those of high-risk patients (SEARCH, P = .003; JHH, P < .001).
  
  
  CONCLUSIONS
  Patients with cT2c disease without other high-risk features had outcomes similar to the outcomes of patients with intermediate-risk PC and significantly better than the outcomes of patients with high-risk PC. These findings suggest that men with cT2c disease should be considered to be at intermediate risk.
authors.affiliation: Medical College of Georgia, Georgia Regents University, Augusta, Georgia.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Klaassen
authors.forename: Abhay A
authors.initials: AA
authors.lastname: Singh
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Howard
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Feng
authors.forename: Bruce
authors.initials: B
authors.lastname: Trock
authors.forename: Martha K
authors.initials: MK
authors.lastname: Terris
authors.forename: William J
authors.initials: WJ
authors.lastname: Aronson
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Cooperberg
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Amling
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kane
authors.forename: Alan
authors.initials: A
authors.lastname: Partin
authors.forename: Misop
authors.initials: M
authors.lastname: Han
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000473:pathology* / Q000517:prevention & control; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000601:surgery; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors
keywords: D'Amico risk stratification; Gleason score; biochemical recurrence; clinical staging; prostate cancer; prostate-specific antigen; radical prostatectomy