title: Limitations in Predicting Organ Confined Prostate Cancer in Patients with Gleason Pattern 4 on Biopsy: Implications for Active Surveillance.
abstract: In prostate cancer biopsy Gleason score predicts stage and helps determine active surveillance suitability. Evidence suggests that small incremental differences in the quantitative percent of Gleason pattern 4 on biopsy stratify disease extent, biochemical failure following surgery and eligibility for active surveillance. We explored the overall quantitative percent of Gleason pattern 4 levels and adverse outcomes in patients with low and intermediate risk prostate cancer to whom active surveillance may be offered under expanded criteria.
  
  
  
  We analyzed the records of patients with biopsy Gleason score 6 (3 + 3) or 7 (3 + 4) who underwent radical prostatectomy from January 2008 to August 2015. Age, prostate specific antigen, Gleason score, quantitative percent of Gleason pattern 4, overall percent positive cores (percent of prostate cancer) and clinical stage were explored as predictors of nonorgan confined disease and time to failure after radical prostatectomy.
  
  
  
  In 1,255 patients biopsy Gleason score 7 (3 + 4) was associated with T3 or greater disease at radical prostatectomy in 35.0% compared with Gleason score 6 (3 + 3) in 19.0% (p <0.001). On multivariate analysis for each quantitative percent of Gleason pattern 4 increase there were 2% higher odds of T3 or greater disease (OR 1.02, 95% CI 1.01-1.04, p <0.001). When stratified, patients with Gleason score 7 (3 + 4) only approximated the pT3 rates of Gleason score 6 (3 + 3) when prostate specific antigen was less than 8 ng/ml and the percent of prostate cancer was less than 15%. In those cases the quantitative percent of Gleason pattern 4 had less effect. Time to failure after radical prostatectomy was worse in Gleason score 7 (3 + 4) than 6 (3 + 3) cases.
  
  
  
  The quantitative percent of Gleason pattern 4 helps predict advanced disease and Gleason score 7 (3 + 4) is associated with worse outcomes. However, the impact of the quantitative percent of Gleason pattern 4 on adverse pathological and clinical outcomes is best used in combination with prostate specific antigen, age and disease volume since each has a greater impact on predicting nonorgan confined disease. The calculated absolute risk of T3 or greater can be used in shared decision making on prostate cancer treatment by patients and clinicians.
authors.affiliation: Division of Urology, Department of Surgical Oncology, University Health Network, University of Toronto, Ontario, Canada. Electronic address: Nathan.perlis@uhn.ca.
authors.forename: Nathan
authors.initials: N
authors.lastname: Perlis
authors.affiliation: Division of Urology, Department of Surgical Oncology, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Rashid
authors.initials: R
authors.lastname: Sayyid
authors.affiliation: Department of Pathology, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Evans
authors.affiliation: Department of Pathology, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Theodorus
authors.initials: T
authors.lastname: Van Der Kwast
authors.affiliation: Joint Department of Medical Imaging, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Ants
authors.initials: A
authors.lastname: Toi
authors.affiliation: Division of Urology, Department of Surgical Oncology, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Antonio
authors.initials: A
authors.lastname: Finelli
authors.affiliation: Division of Urology, Department of Surgical Oncology, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Girish
authors.initials: G
authors.lastname: Kulkarni
authors.affiliation: Division of Urology, Department of Surgical Oncology, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Rob
authors.initials: R
authors.lastname: Hamilton
authors.affiliation: Division of Urology, Department of Surgical Oncology, University Health Network, University of Toronto, Ontario, Canada; Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Zlotta
authors.affiliation: Division of Urology, Department of Surgical Oncology, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Trachtenberg
authors.affiliation: Joint Department of Medical Imaging, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Sangeet
authors.initials: S
authors.lastname: Ghai
authors.affiliation: Division of Urology, Department of Surgical Oncology, University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Fleshner
mesh_terms: D000368:Aged; D001707:Biopsy, Needle; D002170:Canada; D016208:Databases, Factual; D018572:Disease-Free Survival; D055088:Early Detection of Cancer; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009864:Ontario; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000379:methods* / Q000401:mortality; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D057832:Watchful Waiting / Q000379:methods*
chemical_list: D017430:Prostate-Specific Antigen
keywords: neoplasm grading; prognosis; prostatectomy; prostatic neoplasms; watchful waiting