title: Factors influencing disease progression of prostate cancer under active surveillance: a McGill University Health Center cohort.
abstract: OBJECTIVE
  To evaluate the clinical and pathological factors influencing the risk of disease progression in a cohort of patients with low-intermediate risk prostate cancer under active surveillance (AS).
  
  
  METHODS
  We studied 300 patients diagnosed between 1992 and 2012 with prostate adenocarcinoma with favourable parameters or who refused treatment and were managed with AS. Of those, 155 patients with at least one repeat biopsy and no progression criteria at the time of the diagnosis were included for statistical analyses. Patients were followed every 3-6 months for prostate-specific antigen (PSA) measurement and physical examination. Patients were offered repeat prostatic biopsy every year. Disease progression was defined as the presence of one or more of the following criteria: ≥ 3 positive cores, >50% of cancer in at least one core, and a predominant Gleason pattern of 4.
  
  
  RESULTS
  For the 155 patients, the mean (sd) age at diagnosis was 67(7) years; the median (interquartile range) follow-up was 5.4(3.6-9.5) years. Of these, 67, 25, six, and two patients had two, three, four, and five repeat biopsies, respectively. At baseline, 11 (7%) patients had a Gleason score of 3+4, while the remaining 144 (93%) patients had a Gleason score of ≤ 6. In all, 50 (32.3%) patients had disease progression on repeat biopsies, with a median progression-free survival time of 7 years. The rate of disease progression decreased after the second repeat biopsy. The 5-year overall survival rate was 100%. Having a PSA density (PSAD) of >0.15 ng/mL/mL, >1 positive core, and Gleason score >6 at the time of the diagnosis was associated with a significantly higher rate of disease progression on univariate analysis (P < 0.05), while a maximum percentage of cancer in any core of >10% showed a trend toward significance for a higher progression rate (P = 0.054). On multivariate analysis, only the presence of a PSAD of >0.15 ng/mL/mL remained significant for a higher progression rate (P < 0.05). Of the 155 patients, five (3.2%) subsequently received radiotherapy, 13 (8.4%) received hormonal therapy, and 13 (8.4%) underwent radical prostatectomy.
  
  
  CONCLUSIONS
  AS is a suitable management option for patients with clinically low-risk prostate cancer. A PSAD of >0.15 ng/mL/mL is an important predictor for disease progression.
authors.affiliation: Division of Urology, Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Ghassan A
authors.initials: GA
authors.lastname: Barayan
authors.affiliation: Department of Pathology, McGill University, Montreal, QC, Canada.
authors.forename: Fadi
authors.initials: F
authors.lastname: Brimo
authors.affiliation: Department of Pathology, McGill University, Montreal, QC, Canada.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Bégin
authors.affiliation: Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: Hanley
authors.affiliation: Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Division of Urology, Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Wassim
authors.initials: W
authors.lastname: Kassouf
authors.affiliation: Division of Urology, Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Armen G
authors.initials: AG
authors.lastname: Aprikian
authors.affiliation: Division of Urology, Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Tanguay
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality / Q000473:pathology*; 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; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology*; D012307:Risk Factors; D015996:Survival Rate; D057832:Watchful Waiting
chemical_list: D017430:Prostate-Specific Antigen
keywords: PSAD; active surveillance; adenocarcinoma; biopsy; prostate cancer; risk factor