New test may solve the specificity and false-positive problems of the PSA test for prostate cancer

The recent FDA approval of the IsoPSA blood test may represent a notable advancement in prostate cancer screening and diagnosis. Developed by Cleveland Diagnostics, the in vitro diagnostic instrument is designed to assist clinicians in making more informed decisions regarding the necessity of proceeding with an invasive prostate biopsy.

The conventional screening method, the prostate-specific antigen (PSA) blood test, quantifies the level of the PSA protein in the bloodstream. However, the conventional method lacks specificity; elevated PSA levels may result from factors other than high-grade cancer, such as infections or benign prostatic hyperplasia. This limitation results in a significant number of false positive outcomes. The National Cancer Institute says on a webpage about the PSA test that approximately 6% to 7% of men have a false-positive PSA test on any round of testing. The citation for that figure is, though, an older study published in 2008 in BJU International.

The lack of specificity results in a significant diagnostic gap. Although tissue biopsy remains the sole definitive method for diagnosing prostate cancer, approximately 75% of the estimated one million follow-up tests conducted annually yield negative results for high-grade disease (Gleason score of 7 or greater). A negative biopsy is good news and may give some men peace of mind, but all those biopsies also mean that many men are experiencing an invasive and expensive procedure that finds no cancer.

Unlike the conventional PSA test, IsoPSA examines the structural features, or isoforms, of the PSA protein in the bloodstream to detect prostate cancer-specific structural variants. This method yields a more precise risk index score by differentiating benign PSA elevations from those indicative of high-grade cancer.

Arnon Chait, Ph.D., MBA, president and CEO of Cleveland Diagnostics, stated in a news release that “FDA approval of the IsoPSA kit represents an important advancement in the company's efforts to support physicians and patients in early cancer detection, when treatment is most effective.”

Clinical studies substantiate its effectiveness, indicating that IsoPSA surpasses total PSA and % free PSA in diagnostic accuracy. Improved accuracy enables physicians to reliably assess and categorize risk. They can identify high-risk patients requiring intervention or closer surveillance, while also confidently averting unnecessary biopsies or extending biopsy intervals for patients classified as lower risk. One study estimated that IsoPSA could potentially prevent 46% of biopsies conducted for the detection of high-grade prostate cancer in patients classified as low risk. The test is also simple to order, as it does not require a digital rectal exam and preserves its accuracy even when patients are taking medication for benign prostatic hyperplasia.

The importance of the approved test is emphasized by its official endorsement in leading clinical guidelines. IsoPSA is presently incorporated into the guidelines for the NCCN Early Prostate Cancer Detection and the AUA/SUO Early Detection of Prostate Cancer.