FDA Approves Novel Blood-Based Assay to Stratify Prostate Cancer Biopsy Risk

The FDA has granted premarket approval (PMA) to the IsoPSA test, a novel, blood-based in vitro diagnostic kit designed to assist clinicians in deciding whether to proceed with prostate biopsy in men aged 50 years and older who present with elevated prostate-specific antigen (PSA) levels.¹

This approval marks a significant advancement in prostate cancer risk stratification, offering a new tool to distinguish between benign PSA elevations and those attributable to high-grade, clinically significant disease (Gleason score ≥7).

The IsoPSA test leverages the proprietary IsoClear™ platform developed by Cleveland Diagnostics, Inc, to analyze the structural characteristics, or isoforms, of the PSA protein rather than simply measuring its concentration. The existing clinical limitations of standard PSA testing—namely its lack of specificity for cancer and inability to reliably distinguish indolent from aggressive disease—often lead to substantial rates of unnecessary prostate biopsies.

It is estimated that up to 75% of prostate biopsies performed annually in the US fail to detect high-grade cancer, exposing patients to associated risks, anxiety, and health care costs. The approval of the IsoPSA test addresses this diagnostic gap by providing a risk index score designed to offer enhanced clarity regarding the likelihood of high-grade prostate cancer presence.

“As a practicing urologist, I see firsthand how the limitations of current PSA testing can lead to unnecessary procedures and anxiety for patients and appreciate the critical need for early and accurate risk assessment and testing," said Aaron Berger, chief medical officer and director of Clinical Research at Associated Urological Specialists in Chicago, Illinois, in a news release. "IsoPSA represents a meaningful advancement, giving physicians a tool that improves risk assessment and helps us make more informed biopsy decisions with greater confidence."

Integration into Current Guidelines and Future Outlook

The IsoPSA test’s utility has already gained recognition within the urologic oncology community, leading to its inclusion in key diagnostic guidelines, including those published by the National Comprehensive Cancer Network (NCCN) and the American Urological Association (AUA)/Society of Urologic Oncology (SUO).¹ This acceptance, prior to PMA, underscores the perceived clinical value of shifting the diagnostic paradigm from simple concentration-based measurement to structural proteomic assessment.

The ability of the IsoPSA test to function independently of confounding factors common in older patients, such as benign prostatic hyperplasia medication use, further solidifies its potential role as a robust tool for improved risk stratification. By providing a more accurate assessment of aggressive disease risk, the adoption of the IsoPSA test is expected to decrease overdiagnosis of clinically insignificant lesions while ensuring that patients who require curative intervention are reliably identified.

REFERENCES

1. FDA Approves IsoPSA® -- Cleveland Diagnostics’ Novel Blood-Based Prostate Cancer Test. News release. Cleveland Diagnostics, Inc. December 1, 2025. Accessed December 1, 2025. https://tinyurl.com/hnkbjfm7

2. Klein EA, Partin A, Lotan Y, 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;40(9):408.e9-408.e18. doi:10.1016/j.urolonc.2022.06.002.