title: A negative confirmatory biopsy among men on active surveillance for prostate cancer does not protect them from histologic grade progression.
abstract: BACKGROUND
  Many men (21-52%) are reported to have no cancer on the second, also known as the confirmatory, biopsy (B2) for prostate cancer active surveillance (AS). If these men had a reduced risk of pathologic progression, particularly grade related, the intensity of their follow-up could be decreased.
  
  
  OBJECTIVE
  To investigate if men with no cancer on B2 are less likely to undergo subsequent pathologic progression.
  
  
  METHODS
  Men were identified from our tertiary care center AS prostate cancer database (1995-2012). Eligibility criteria were prostate-specific antigen (PSA) ≤ 10, cT2 or lower, no Gleason grade 4 or 5, three or fewer positive cores, and no core >50% involved. Only patients with three or more biopsies were selected and then dichotomized on cancer status (yes or no) at B2.
  Pathologic progression was defined as grade (advancement in Gleason score) and/or volume (more than three positive cores, >50% core involved). Progression-free survival was compared. Predictors of progression were investigated using a Cox proportional hazards model.
  
  
  CONCLUSIONS
  Of the 286 patients remaining on AS after B2, 149 (52%) had no cancer and 137 (48%) had cancer. The median follow-up after B2 was 41 mo (interquartile range [IQR]: 26.5-61.9). Progression-free survival at 5 yr was 85.2% versus 67.3% for negative B2 versus cancer on B2, respectively (p = 0.002). Men with no cancer at B2 had a 53% reduction in risk of subsequent progression (hazard ratio [HR]: 0.47; 95% confidence interval [CI], 0.29-0.77; p = 0.003). Subanalysis showed prognostic indicators of volume-related progression were absence of cancer (HR: 0.36; 95% CI, 0.20-0.62; p = 0.0006) and PSA density (HR: 1.79; 95% CI, 1.12-2.89; p = 0.01). The only predictor of grade-related progression was age (HR: 1.05; 95% CI, 1.00-1.10; p = 0.04). Retrospective analysis was the major limitation of the study.
  
  
  CONCLUSIONS
  Absence of cancer on B2 is associated with a significantly decreased risk of volume-related but not grade-related progression. This must be considered when counseling men on AS.
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Lih-Ming
authors.initials: LM
authors.lastname: Wong
authors.affiliation: Department of Medicine, University Health Network, Toronto, Canada.
authors.forename: Shabbir M H
authors.initials: SM
authors.lastname: Alibhai
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Trottier
authors.affiliation: Department of Medicine, University Health Network, Toronto, Canada.
authors.forename: Narhari
authors.initials: N
authors.lastname: Timilshina
authors.affiliation: Department of Pathology, University Health Network, Toronto, Canada.
authors.forename: Theodorus
authors.initials: T
authors.lastname: Van der Kwast
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Zlotta
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Lawrentschuk
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Girish
authors.initials: G
authors.lastname: Kulkarni
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Hamilton
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ferrara
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Margel
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Trachtenberg
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jewett
authors.affiliation: Department of Radiology, University Health Network, Toronto, Canada.
authors.forename: Ants
authors.initials: A
authors.lastname: Toi
authors.affiliation: Department of Pathology, University Health Network, Toronto, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Evans
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Fleshner
authors.affiliation: Division of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, Canada. Electronic address: antonio.finelli@uhn.ca.
authors.forename: Antonio
authors.initials: A
authors.lastname: Finelli
mesh_terms: D000367:Age Factors; D000368:Aged; D018450:Disease Progression; D018572:Disease-Free Survival; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009929:Organ Size; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000628:therapy*; D012189:Retrospective Studies; D057832:Watchful Waiting
chemical_list: D017430:Prostate-Specific Antigen
keywords: Active surveillance; Biopsy; Pathology; Progression; Prostate cancer; Reclassification