title: Biopsy features associated with prostate cancer progression in active surveillance patients: comparison of three statistical models.
abstract: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Active surveillance is an established management option for patients with favourable-risk prostate cancer. However, about 25-30% of active surveillance patients demonstrate biopsy progression within the first 3-5 years of follow-up. Although several factors, such as the results of the diagnostic and surveillance biopsies, are known to be associated with the risk of progression, our ability to accurately predict this risk remains limited. Our analysis demonstrated that the overall number of positive cores in the diagnostic and first surveillance biopsies is strongly associated with the risk of progression in active surveillance patients. Furthermore, combined results of diagnostic and first surveillance biopsies provide more information about the probability of progression than they do separately. The most important variable affecting the progression-free survival was the overall number of cores positive for cancer. By 3 years of active surveillance, most of the patients who had four positive cores in the diagnostic and surveillance biopsies progressed, while those who had only one positive core had an excellent prognosis. These findings could be used to improve the accuracy of assessments of the prognosis of patients with low-risk prostate cancer and to help them make informed decisions about their treatment.
  
  
  OBJECTIVE
  To analyse the prognostic importance of information provided by the diagnostic biopsy, the first surveillance biopsy and a combination thereof to identify active surveillance patients with a particularly high risk of progression.
  
  
  METHODS
  The present study included 161 active surveillance patients who had at least two surveillance biopsies. The first surveillance biopsy was performed within 1 year of the diagnosis. Further surveillance biopsies usually took place every 1-2 years. Progression on the surveillance biopsy was defined as the presence of Gleason 4/5 cancer, > two positive cores or >20% involvement of any core. Cox proportional hazards regression analysis was used to examine the relationship between biopsy characteristics and progression. Three distinct statistical models were built using characteristics of diagnostic biopsies, surveillance biopsies, and a combination thereof. Harrell's c-index was used to quantify the predictive accuracy of each multivariate Cox model.
  
  
  RESULTS
  The median follow-up was 3.6 years; 46 (28.6%) patients progressed. In multivariate analysis the major factor associated with progression was the number of positive cores. The model based on the combined results of diagnostic and first surveillance biopsies was significantly more predictive than the models based on the individual results of each biopsy. Patients with four positive cores in the diagnostic and first surveillance biopsies had estimated 5-year progression rate of 100%.
  
  
  CONCLUSIONS
  The total number of positive cores in the diagnostic and first surveillance biopsies provides important information about the risk of prostate cancer progression in active surveillance patients.
authors.affiliation: Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA. viremashvili@med.miami.edu
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Iremashvili
authors.forename: Murugesan
authors.initials: M
authors.lastname: Manoharan
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Rosenberg
authors.forename: Mark S
authors.initials: MS
authors.lastname: Soloway
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001707:Biopsy, Needle; D015331:Cohort Studies; D016208:Databases, Factual; D018450:Disease Progression; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D016019:Survival Analysis; D013997:Time Factors; D014481:United States; D057832:Watchful Waiting / Q000379:methods*
chemical_list: D017430:Prostate-Specific Antigen