Clinical validation of IsoPSA, a single parameter, structure-focused assay for improved detection of prostate cancer: A prospective, multicenter study.


Journal

Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460

Informations de publication

Date de publication:
09 2022
Historique:
received: 10 02 2022
revised: 01 06 2022
accepted: 02 06 2022
pubmed: 16 7 2022
medline: 31 8 2022
entrez: 15 7 2022
Statut: ppublish

Résumé

IsoPSA is a blood-based test that assesses prostate cancer (CaP) risk by partitioning and detecting cancer-specific structural isoforms of prostate specific antigen (PSA) with an aqueous 2- phase system. To validate the diagnostic performance of IsoPSA for High-Grade CaP and Any CaP risk on biopsy in men age ≥ 50 with total PSA ≥ 4 ng/ml. Prospective, multicenter study of 888 men scheduled for prostate biopsy at 8 academic and community sites between August 2015 and August 2020. IsoPSA test. Receiver operating characteristic and likelihood ratio analysis used to validate diagnostic performance for previously established IsoPSA Index cutoffs for High-Grade CaP (Gleason Score ≥ 7) and Any CaP (Gleason Score ≥ 6), compare IsoPSA to total PSA and % free PSA, and evaluate subgroups (total PSA 4-10 ng/ml, total PSA > 10 ng/ml, biopsy naïve, prior negative biopsy). The disease prevalence was 35.6% (High-Grade CaP) and 58.9% (Any CaP). The area under the receiver operating characteristic curve was 0.783 (High-Grade CaP) and 0.770 (Any CaP). IsoPSA outperformed total PSA and % free PSA on area under the receiver operating characteristic curve, specificity, positive and negative predictive value at similar sensitivity. Using selected IsoPSA Index cutoffs, an estimated 46% (High-Grade CaP) and 42% (Any CaP) of biopsies could be avoided in low-risk patients. IsoPSA displayed statistically informative likelihood ratio-based predictive characteristics. IsoPSA maintained accuracy in clinically relevant subgroups. IsoPSA diagnostic performance and predictive value is validated for High-Grade CaP and Any CaP in men age ≥ 50 with total PSA ≥ 4 ng/ml undergoing diagnostic biopsy. IsoPSA outperforms total and % free PSA in discriminating the risk of prostate cancer on biopsy. IsoPSA has the potential to reduce unnecessary biopsies and improve the risk-benefit ratio for CaP early detection.

Sections du résumé

BACKGROUND
IsoPSA is a blood-based test that assesses prostate cancer (CaP) risk by partitioning and detecting cancer-specific structural isoforms of prostate specific antigen (PSA) with an aqueous 2- phase system.
OBJECTIVE
To validate the diagnostic performance of IsoPSA for High-Grade CaP and Any CaP risk on biopsy in men age ≥ 50 with total PSA ≥ 4 ng/ml.
DESIGN, SETTING, AND PARTICIPANTS
Prospective, multicenter study of 888 men scheduled for prostate biopsy at 8 academic and community sites between August 2015 and August 2020.
INTERVENTION
IsoPSA test.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Receiver operating characteristic and likelihood ratio analysis used to validate diagnostic performance for previously established IsoPSA Index cutoffs for High-Grade CaP (Gleason Score ≥ 7) and Any CaP (Gleason Score ≥ 6), compare IsoPSA to total PSA and % free PSA, and evaluate subgroups (total PSA 4-10 ng/ml, total PSA > 10 ng/ml, biopsy naïve, prior negative biopsy).
RESULTS AND LIMITATIONS
The disease prevalence was 35.6% (High-Grade CaP) and 58.9% (Any CaP). The area under the receiver operating characteristic curve was 0.783 (High-Grade CaP) and 0.770 (Any CaP). IsoPSA outperformed total PSA and % free PSA on area under the receiver operating characteristic curve, specificity, positive and negative predictive value at similar sensitivity. Using selected IsoPSA Index cutoffs, an estimated 46% (High-Grade CaP) and 42% (Any CaP) of biopsies could be avoided in low-risk patients. IsoPSA displayed statistically informative likelihood ratio-based predictive characteristics. IsoPSA maintained accuracy in clinically relevant subgroups.
CONCLUSIONS
IsoPSA diagnostic performance and predictive value is validated for High-Grade CaP and Any CaP in men age ≥ 50 with total PSA ≥ 4 ng/ml undergoing diagnostic biopsy. IsoPSA outperforms total and % free PSA in discriminating the risk of prostate cancer on biopsy.
PATIENT SUMMARY
IsoPSA has the potential to reduce unnecessary biopsies and improve the risk-benefit ratio for CaP early detection.

Identifiants

pubmed: 35840465
pii: S1078-1439(22)00220-4
doi: 10.1016/j.urolonc.2022.06.002
pii:
doi:

Substances chimiques

Prostate-Specific Antigen EC 3.4.21.77

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

408.e9-408.e18

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Eric A Klein (EA)

Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, OH; Stanford University Distinguished Careers Institute, Stanford, CA. Electronic address: kleine@ccf.org.

Alan Partin (A)

Johns Hopkins James Buchanan Brady Urological Institute, Baltimore, MD.

Yair Lotan (Y)

University of Texas Southwestern Medical Center Department of Urology, Dallas TX.

Jack Baniel (J)

Rabin Medical Center Department of Urology, Petah Tikvah, Israel.

Martin Dineen (M)

Advanced Urology Institute, Daytona Beach, FL.

Jason Hafron (J)

Michigan Institute of Urology, West Bloomfield, MI.

Kannan Manickam (K)

Chesapeake Urology Associates, Baltimore, MD.

Marc Pliskin (M)

The Urology Group, Cincinnati, OH.

Matthew Wagner (M)

Kaiser Permanente Northwest, Clackamas, OR.

Aimee Kestranek (A)

Cleveland Diagnostics, Inc., Cleveland, OH.

Mark Stovsky (M)

Cleveland Diagnostics, Inc., Cleveland, OH.

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