title: The Single-parameter, Structure-based IsoPSA Assay Demonstrates Improved Diagnostic Accuracy for Detection of Any Prostate Cancer and High-grade Prostate Cancer Compared to a Concentration-based Assay of Total Prostate-specific Antigen: A Preliminary Report.
abstract: IsoPSA is a serum-based assay that predicts prostate cancer (PCa) risk by partitioning isoforms of prostate-specific antigen (PSA) with an aqueous two-phase reagent.
  
  
  
  To determine the diagnostic accuracy of IsoPSA in identifying the presence or absence of PCa and the presence of high-grade disease in a contemporary biopsy cohort.
  
  
  
  Multicenter prospective study of 261 men scheduled for prostate biopsy at five academic and community centers in the USA enrolled between August 2015 and December 2016.
  
  
  
  Performance of the IsoPSA assay.
  
  
  
  Discrimination power was evaluated using receiver operating characteristic (ROC) analysis. The outcome of the IsoPSA assay was transformed into risk probability using logistic regression. Decision curve analysis (DCA) was used to compare the net benefit of IsoPSA against other clinical protocols.
  
  
  
  The overall prevalence was 53% for any PCa and 34% for high-grade PCa. The area under the ROC curve was 0.79 for any cancer versus none and 0.81 for high-grade PCa versus low-grade PCa/benign histology. In this preliminary study, DCA revealed a superior net benefit of IsoPSA against no biopsy, all biopsy, and the modified Prostate Cancer Prevention Trial Risk Calculator 2.0. At a cutoff selected to recommend biopsy, IsoPSA demonstrated a 48% reduction in false-positive biopsies; at a cutoff selected to identity men at low risk of high-grade disease, there was a 45% reduction in the false-positive rate.
  
  
  
  The structure-based IsoPSA assay outperformed concentration-based PSA measurement, and provided a net benefit against other protocols. Once validated, clinical use of IsoPSA could significantly reduce unnecessary biopsies while identifying patients needing treatment.
  
  
  
  The IsoPSA assay outperformed prostate-specific antigen in predicting the overall risk of prostate cancer and the risk of clinically significant cancer in a preliminary study. The IsoPSA assay could assist in determining the need for prostate biopsy for patients.
authors.affiliation: Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: kleine@ccf.org.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.affiliation: Cleveland Diagnostics, Cleveland, OH, USA.
authors.forename: Arnon
authors.initials: A
authors.lastname: Chait
authors.affiliation: Pathology and Research Department, Michigan Institute of Urology, St Clair Shores, MI, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Hafron
authors.affiliation: Pathology and Research Department, Michigan Institute of Urology, St Clair Shores, MI, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kernen
authors.affiliation: Chesapeake Urology Associates, Baltimore, MD, USA.
authors.forename: Kannan
authors.initials: K
authors.lastname: Manickam
authors.affiliation: Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stephenson
authors.affiliation: Kaiser Permanente Northwest, Clackamas, OR, USA.
authors.forename: Mathew
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Louis Stokes VA Medical Center, Cleveland, OH, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Cleveland Diagnostics, Cleveland, OH, USA.
authors.forename: Aimee
authors.initials: A
authors.lastname: Kestranek
authors.affiliation: Cleveland Diagnostics, Cleveland, OH, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Zaslavsky
authors.affiliation: Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA; Cleveland Diagnostics, Cleveland, OH, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Stovsky
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001706:Biopsy; D005189:False Positive Reactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D000074286:Preliminary Data; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D020033:Protein Isoforms / Q000097:blood; D012372:ROC Curve
chemical_list: D020033:Protein Isoforms; D017430:Prostate-Specific Antigen
keywords: Biomarker; Prostate cancer; Prostate-specific antigen