title: The percent of positive biopsy cores improves prediction of prostate cancer-specific death in patients treated with dose-escalated radiotherapy.
abstract: OBJECTIVE
  To examine the prognostic utility of the percentage of positive cores (PPC) at the time of prostate biopsy for patients treated with dose-escalated external beam radiation therapy.
  
  
  METHODS
  We performed a retrospective analysis of patients treated at the University of Michigan Medical Center to at least 75 Gy. Patients were stratified according to PPC by quartile, and freedom from biochemical failure (nadir + 2 ng/mL), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS) were assessed by log-rank test. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cut point for PPC stratification. Finally, Cox proportional hazards multivariate regression was used to assess the impact of PPC on clinical outcome when adjusting for National Comprehensive Cancer Network (NCCN) risk group and androgen deprivation therapy.
  
  
  RESULTS
  PPC information was available for 651 patients. Increasing-risk features including T stage, prostate-specific antigen, Gleason score, and NCCN risk group were all directly correlated with increasing PPC. On log-rank evaluation, all clinical endpoints, except for OS, were associated with PPC by quartile, with worse clinical outcomes as PPC increased, with the greatest impact seen in the highest quartile (>66.7% of cores positive). ROC curve analysis confirmed that a cut point using two-thirds positive cores was most closely associated with CSS (p = 0.002; area under ROC curve, 0.71). On univariate analysis, stratifying patients according to PPC less than or equal to 66.7% vs. PPC greater than 66.7% was prognostic for freedom from biochemical failure (p = 0.0001), FFM (p = 0.0002), and CSS (p = 0.0003) and marginally prognostic for OS (p = 0.055). On multivariate analysis, after adjustment for NCCN risk group and androgen deprivation therapy use, PPC greater than 66.7% increased the risk for biochemical failure (p = 0.0001; hazard ratio [HR], 2.1 [95% confidence interval (CI), 1.4-3.0]) and FFM (p = 0.05; HR, 1.7 [95% CI, 1.1-2.9]) and marginally increased the risk for CSS (p = 0.057; HR, 2.1 [95% CI, 1.0-4.6]).
  
  
  CONCLUSIONS
  PPC at the time of biopsy adds prognostic value for clinically meaningful endpoints for patients treated with dose-escalated radiation therapy. This was particularly true for NCCN-defined intermediate- and high-risk patients.
authors.affiliation: University of Michigan Medical Center, Ann Arbor, MI 48109-5010, USA.
authors.forename: Yushen
authors.initials: Y
authors.lastname: Qian
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.forename: Schuyler
authors.initials: S
authors.lastname: Halverson
authors.forename: Kevin
authors.initials: K
authors.lastname: Blas
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001707:Biopsy, Needle; D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D012372:ROC Curve; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000726:Androgen Antagonists