title: Occult High-risk Disease in Clinically Low-risk Prostate Cancer with ≥50% Positive Biopsy Cores: Should National Guidelines Stop Calling Them Low Risk?
abstract: OBJECTIVE
  To identify contemporary, clinically low-risk patients with ≥50% cores positive and compare the risk of upgrading at prostatectomy with other low- or intermediate-risk patients.
  
  
  METHODS
  We studied 14,902 patients with prostate cancer in the Surveillance, Epidemiology, and End Results database in 2010-2011 treated with prostatectomy. Patients were categorized by National Comprehensive Cancer Network clinical risk groups, separating low-risk patients by percent positive biopsy cores (PBC). We measured incidence of pathologic high-risk disease, defined as pT3a-T4 or Gleason 8-10, and multivariable logistic regression was used to determine if patients with clinical low-risk disease and ≥50% PBC were similar to other low- or intermediate-risk patients. This analysis was repeated with favorable and unfavorable intermediate risk.
  
  
  RESULTS
  At prostatectomy, 9.2% of clinically low-risk patients with <50% PBC, 18.6% of clinically low-risk patients with ≥50% PBC, and 27.6% of clinically intermediate-risk patients had occult, high-risk disease (P <.001). On multivariable logistic regression, low-risk patients with ≥50% PBC were more likely than low-risk patients with <50% PBC to have pathologic high-risk disease (adjusted odds ratio [AOR] 2.28, 95% confidence interval 1.90-2.73, P <.001), had similar risk to favorable intermediate patients overall (AOR 1.09, 0.91-1.31, P = .33), and had higher risk than favorable intermediate patients aged over 60 years (AOR 1.28, 1.00-1.64, P = .04). Low-risk patients with ≥50% PBC had a mean tumor size similar to unfavorable intermediate-risk patients (21.3 vs 21.0 mm, P = .82).
  
  
  CONCLUSIONS
  Nearly 1 in 5 clinically low-risk prostate cancer patients with ≥50% PBC harbor occult pT3a-T4 or Gleason 8-10, suggesting that national guidelines should not classify low-risk patients with ≥50% cores positive as "low risk," and patients should be made aware of this excess risk if considering active surveillance.
authors.affiliation: Harvard Medical School, Boston, MA.
authors.forename: Kathryn T
authors.initials: KT
authors.lastname: Dinh
authors.affiliation: Harvard Medical School, Boston, MA.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Muralidhar
authors.affiliation: Harvard Medical School, Boston, MA.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Mahal
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Nezolosky
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA.
authors.forename: Clair J
authors.initials: CJ
authors.lastname: Beard
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Martin
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Orio
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
authors.affiliation: Division of Urology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Brigham and Women's Hospital, Boston, MA.
authors.forename: Quoc-Dien
authors.initials: QD
authors.lastname: Trinh
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA. Electronic address: pnguyen@LROC.harvard.edu.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000453:epidemiology; D000368:Aged; D001706:Biopsy; D019983:Guideline Adherence; D017408:Guidelines as Topic; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000601:surgery; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D018426:SEER Program; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology