TY - JOUR
T1 - Clinical validation of IsoPSA, a single parameter, structure-focused assay for improved detection of prostate cancer
T2 - A prospective, multicenter study
AU - Klein, Eric A.
AU - Partin, Alan
AU - Lotan, Yair
AU - Baniel, Jack
AU - Dineen, Martin
AU - Hafron, Jason
AU - Manickam, Kannan
AU - Pliskin, Marc
AU - Wagner, Matthew
AU - Kestranek, Aimee
AU - Stovsky, Mark
N1 - Funding Information:
Disclaimer, IsoPSA received FDA Breakthrough Device Designation in 2019. The in vitro diagnostic device (IVD) version of the IsoPSA assay is currently under review by the U.S. Food and Drug Administration (FDA). Author Access to Data, Eric Klein, MD (principal investigator) had full access to all the data in the study and accepts responsibility for the integrity of the data and the accuracy of the data analysis. Eric Klein, MD (Cleveland Clinic Glickman Urological and Kidney Institute, Stanford University Distinguished Careers Institute), Mark Stovsky, MD (Cleveland Diagnostics, Inc.), and Aimee Kestranek, BS (Cleveland Diagnostics, Inc.) conducted and are responsible for the data analysis. Authors were not precluded from accessing data in the study or from reviewing/editing the manuscript and they accept responsibility to submit for publication. Cleveland Diagnostics, Inc. provided funding for study logistics and performed IsoPSA on clinical plasma specimens collected at study sites. Cleveland Diagnostics, Inc. participated in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation and review of the manuscript.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Early detection
KW - Prostate cancer
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U2 - 10.1016/j.urolonc.2022.06.002
DO - 10.1016/j.urolonc.2022.06.002
M3 - Article
C2 - 35840465
AN - SCOPUS:85134348390
SN - 1078-1439
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
ER -