Clinical validation of IsoPSA, a single parameter, structure-focused assay for improved detection of prostate cancer: A prospective, multicenter study.
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.
Klein EA, Partin A, Lotan Y, Baniel J, Dineen M, Hafron J, et al. Clinical validation of IsoPSA, a single parameter, structure-focused assay for improved detection of prostate cancer: A prospective, multicenter study. Urol Oncol. 2022 Sep;40(9):408.e9-408.e18. doi: 10.1016/j.urolonc.2022.06.002. PMID: 35840465.