title: Adverse Disease Features in Gleason Score 3 + 4 "Favorable Intermediate-Risk" Prostate Cancer: Implications for Active Surveillance.
abstract: According to a recent National Comprehensive Cancer Network (NCCN) guidelines update, patients with Gleason score (GS) 3 + 4 prostate cancer (PCa) and "favorable intermediate-risk" (FIR) characteristics might be offered active surveillance (AS). However, the risk of unfavorable disease features and its prediction in this subset of patients is not completely understood.
  
  
  
  To identify the risk of unfavorable disease and potential predictors of adverse outcomes among GS 3 + 4 FIR PCa patients.
  
  
  
  The study included patients with biopsy GS 3 + 4 and otherwise fulfilling the NCCN low-risk definition (prostate-specific antigen [PSA] <10 ng/ml, cT2a or lower) undergoing radical prostatectomy (RP) from 2006 to 2014 at a single institution.
  
  
  
  Complete information on PSA, PSA density (PSAD), clinical stage, percentage of positive cores, percentage of maximum surface specimen involvement, and RP pathology were available. GS upgrade and downgrade, non-organ-confined and non-specimen-confined disease, unfavorable disease (pT3-T4 and/or pN1 and/or a pGS ≥4 + 3) were the outcomes. Statistical analysis included descriptive statistics and multivariable logistic regression.
  
  
  
  A total of 156 patients (13.1%) experienced GS upgrade; 201 (16.9%) were downgraded. Overall, 205 men (17.2%) harbored non-organ-confined disease, and 295 (24.8%) had unfavorable disease. Age (odds ratio [OR]: 1.06), percentage surface involvement (OR: 1.01), and PSAD (OR: 1.83) were the only significant predictors of upgrade. Age (OR: 1.05), clinical stage (OR: 1.74), percentage of positive cores >50% (OR 1.57), percentage of surface area (OR: 1.02), and perineural invasion (OR: 1.89) were significant predictors of unfavorable disease at RP. The retrospective design is a limitation.
  
  
  
  AS is a possible option for a subset of men with FIR GS 3 + 4. However, clinical models alone have a limited role in GS upgrade prediction, and alternative tools warrant further investigation.
  
  
  
  Patients with Gleason score 3 + 4 at biopsy, low prostate-specific antigen, and low stage might consider the option of active surveillance, but the use of clinical information alone might be not adequate for thorough risk-adapted counseling.
authors: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors: Alessandro
authors: A
authors: Morlacco
authors: Department of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors: John C
authors: JC
authors: Cheville
authors: Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors: Laureano J
authors: LJ
authors: Rangel
authors: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors: Derek J
authors: DJ
authors: Gearman
authors: Department of Urology, Mayo Clinic, Rochester, MN, USA. Electronic address: Karnes.R@mayo.edu.
authors: R Jeffrey
authors: RJ
authors: Karnes
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016009:Chi-Square Distribution; D000066491:Clinical Decision-Making; D003661:Decision Support Techniques; D006801:Humans; D007610:Kallikreins / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D057832:Watchful Waiting
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Active surveillance; Downgrade; Eligibility; Gleason 3 + 4; Gleason score; Prostate cancer; Radical prostatectomy; Unfavorable disease; Upgrade