INTRODUCTION AND OBJECTIVE:
We present cumulative results describing the clinical performance of IsoPSA, a blood-based, structure-focused assay for high grade prostate cancer, in a large scale, prospective validation trial.
In this validation trial (N = 1093), blood samples were obtained from multiple clinical sites, collected within 30 days prior to prostate biopsy from patients with serum PSA between 4 and 100 ng/ml. IsoPSA was evaluated against TRUS and/or MRI Fusion biopsy results as the gold standard. The prevalence of high grade prostate cancer (PCa) in the study group was 35.3%. The test parameter (IsoPSA Index) was evaluated by ROC analysis in comparison to total PSA and % free PSA.
ROC analysis using the test parameter, IsoPSA Index, resulted in AUC=0.790, sensitivity=90.4%, specificity=47.1%, NPV=90.0% and PPV=48.3% at the established cutoff value (≤6.0) to identify patients at low risk for high-grade PCa. IsoPSA showed superior AUC, specificity, NPV and PPV compared to total PSA, % free PSA, and % free PSA (total PSA 4-10 ng/mL). The AUC, sensitivity and specificity of IsoPSA were stable and durable in both biopsy naïve and prior negative biopsy cohorts. The diagnostic accuracy of IsoPSA was unaffected by the use of alpha 1-blocker (AUC=0.795) and 5-ARI (AUC=0.789) medications. Using IsoPSA, an estimated 47.1% of biopsies targeting high-grade disease could have been avoided in the validation cohort.
IsoPSA displays superior diagnostic accuracy to total PSA and % free PSA in assessing the risk of high-grade PCa. Clinical use of IsoPSA would have resulted in a significant reduction in unneeded biopsies in low risk patients. IsoPSA also displays clinical utility in patients with symptomatic BPH on standard medication regimens.
Source of Funding:
Cleveland Diagnostics, Inc.