EURURO Vol. 72 No. 6

Platinum Priority – Prostate Cancer

Editorial by Devin N. Patel and Stephen J. Freedland on pp. 950–951 of this issue

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

Eric A. Klein

a , * ,

Arnon Chait

b ,

Jason M. Hafron

c ,

Kenneth M. Kernen

c ,

Kannan Manickam

d ,

Andrew J. Stephenson

a ,

Mathew Wagner

e ,

Hui Zhu

f ,

Aimee Kestranek

b ,

Boris Zaslavsky

b ,

Mark Stovsky

a , b

Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA;

Cleveland Diagnostics, Cleveland, OH, USA;

Pathology and Research Department, Michigan Institute of Urology, St Clair Shores, MI, USA;

Chesapeake Urology Associates, Baltimore, MD, USA;

Kaiser

Permanente Northwest, Clackamas, OR, USA;

Louis Stokes VA Medical Center, Cleveland, OH, USA

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 9 4 2 – 9 4 9

available at

www.scienced irect.com

journal homepage:

www.europeanurology.com

Article info

Article history:

Accepted March 17, 2017

Associate Editor:

James Catto

Keywords:

Biomarker

Prostate cancer

Prostate-specific antigen

Abstract

Background:

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.

Objectives:

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.

Design, setting, and participants:

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.

Intervention:

Performance of the IsoPSA assay.

Outcome measurements and statistical analysis:

Discrimination power was evaluated using

receiver operating characteristic (ROC) analysis. The outcome of the IsoPSA assay was trans-

formed into risk probability using logistic regression. Decision curve analysis (DCA) was used to

compare the net benefit of IsoPSA against other clinical protocols.

Results and limitations:

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.

Conclusion:

The structure-based IsoPSA assay outperformed concentration-based PSAmeasure-

ment, and provided a net benefit against other protocols. Once validated, clinical use of IsoPSA

could significantly reduce unnecessary biopsies while identifying patients needing treatment.

Patient summary:

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.

* Corresponding author. Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Ave,

Cleveland, OH 44106, USA. Tel. +1 216 4445601; Fax: +1 216 6364492.

E-mail address:

kleine@ccf.org

(E.A. Klein).

http://dx.doi.org/10.1016/j.eururo.2017.03.025

0302-2838/