title: Do Ultrasensitive Prostate Specific Antigen Measurements Have a Role in Predicting Long-Term Biochemical Recurrence-Free Survival in Men after Radical Prostatectomy?
abstract: OBJECTIVE
  In this study we evaluate an ultrasensitive prostate specific antigen assay in patients with prostate cancer after radical prostatectomy to predict long-term biochemical recurrence-free survival.
  
  
  METHODS
  A total of 754 men who underwent radical prostatectomy and had an undetectable prostate specific antigen after surgery (less than 0.1 ng/ml) were studied. Prostate specific antigen was measured in banked serum specimens with an ultrasensitive assay (Hybritech® PSA, Beckman Coulter Access® 2) using a cutoff of 0.01 ng/ml. Prostate specific antigen was also measured in 44 men after cystoprostatectomy who had no pathological evidence of prostate cancer with the Hybritech assay and with the Quanterix AccuPSA™ assay.
  
  
  RESULTS
  Of the 754 men 17% (131) experienced biochemical recurrence (median 4.0 years). Those men without biochemical recurrence (83%, 623) had a minimum of 5 years of followup (median 11). Prostate specific antigen was less than 0.01 ng/ml in 93.4% of men with no biochemical recurrence, whereas 30.5% of men with biochemical recurrence had a prostate specific antigen of 0.01 ng/ml or greater. On multivariate analysis postoperative prostate specific antigen at a 0.01 ng/ml cutoff, pathological stage and Gleason score, and surgical margins were significant independent predictors of biochemical recurrence risk. Kaplan-Meier estimates for mean biochemical recurrence-free survival were 15.2 years (95% CI 14.9-15.6) for prostate specific antigen less than 0.01 ng/ml and 10.0 years (95% CI 8.4-11.5) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Biochemical recurrence-free rates 11 years after surgery were 86.1% (95% CI 83.2-89.0) for prostate specific antigen less than 0.01 ng/ml and 48.9% (95% CI 37.5-60.3) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Prostate specific antigen concentrations in 44 men after cystoprostatectomy were all less than 0.03 ng/ml, with 95.4% less than 0.01 ng/ml.
  
  
  CONCLUSIONS
  In men with a serum prostate specific antigen less than 0.1 ng/ml after radical prostatectomy a tenfold lower cutoff (0.01 ng/ml) stratified biochemical recurrence-free survival and was a significant independent predictor of biochemical recurrence, as were pathological features. Prostate specific antigen concentrations in men without pathological evidence of prostate cancer suggest that a higher prostate specific antigen concentration (0.03 ng/ml) in the ultrasensitive range may be needed to define the detection threshold.
authors: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland. Electronic address: lsokoll@jhmi.edu.
authors: Lori J
authors: LJ
authors: Sokoll
authors: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Zhen
authors: Z
authors: Zhang
authors: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Daniel W
authors: DW
authors: Chan
authors: James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Adam C
authors: AC
authors: Reese
authors: James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Trinity J
authors: TJ
authors: Bivalacqua
authors: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland; James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Alan W
authors: AW
authors: Partin
authors: James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors: Patrick C
authors: PC
authors: Walsh
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000601:surgery*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
keywords: prostate-specific antigen; prostatectomy; prostatic neoplasms; recurrence