Clinical Evaluation of IsoPSA, a Disease-Specific Biomarker for Prostate Cancer

A novel prostate-specific antigen (PSA) assay could cut in half the number of unnecessary prostate biopsies, while simultaneously arming men and their doctors with improved prognostic information to guide treatment decisions, according to a clinical analysis of the new test.

The IsoPSA™ test, developed by Cleveland Clinic in collaboration with Cleveland Diagnostics, Inc.,* is a serum-based biomarker assay for prostate cancer that interrogates the entire spectrum of structural changes to PSA, which result from disordered cellular processes in prostate cancer.

“These are encouraging results from a testing platform we hope will better equip us with the information needed to find cancer early and treat it appropriately,” says Eric Klein, MD, Chairman of Cleveland Clinic Glickman Urological & Kidney Institute. “Accurate prognostication in prostate cancer is paramount to identifying appropriate treatment, and this test is another milestone in the development of biomarkers that could tell us how likely a cancer is to spread and whether intervention would be preferred over surveillance.”

PSA isoform testing capitalizes on structural changes to PSA that result from dysregulated cellular processes in prostate cancer, an improvement over existing PSA tests that are prostate-specific but not prostate-cancer specific.

According to a preliminary analysis published in European Urology, the new IsoPSA test outperformed standard PSA as both a cancer-no cancer test and a high-grade vs. low-grade test.

Study results

The European Urology study involved 261 men scheduled for prostate biopsy at five academic and community medical centers across the U.S. Overall, 53 percent of participating men were found to have some type of prostate cancer, and 34 percent had high-grade (Gleason ≥ 7) disease.

Result highlights:

• IsoPSA outperformed standard PSA for both cancer detection and detection of high-grade disease
• In detecting cancer, IsoPSA’s area-under-curve (AUC) was 0.79 (95% CI 0.73–0.84), vs. 0.61 (95% CI 0.54–0.67) for total PSA (p < 0.001)
• For detecting high-grade cancer, IsoPSA’s AUC was 0.81 (95% CI 0.74–0.86), vs. 0.69 (95% CI 0.61–0.75) for total PSA (p < 0.005)

“By changing the focus from PSA concentration to PSA variants and structures, we have developed a testing paradigm that returns highly relevant information for providers and patients,” Dr. Klein maintains.

Until final validation is confirmed, IsoPSA is unavailable for routine use, but Dr. Klein is optimistic that ongoing evaluation of the test will lead to the conclusion that it provides superior detection and prognostication over current testing technologies, which include imaging and PSA testing.

Benefits of isoform testing

PSA testing is unique among molecular biomarkers in that it is specific to the gland being evaluated. The drawback is that it is tissue-specific, but not cancer-specific, and often leads to overtreatment and unnecessary biopsies.

In other words, many pathologies and biological processes unrelated to cancer (i.e. prostatitis, benign prostate hyperplasia and urinary tract infection) can elevate serum PSA levels.

IsoPSA, on the other hand, has been developed to evaluate structural changes in the PSA isoforms that correlate with prostate cancer. This approach not only reduces the number of false positives, it also allows providers a window into the cancer grade before deciding on whether a biopsy is indicated.

Benefits over traditional PSA testing include:

• Agnostic to the presence or absence of specific PSA isoforms
• Conditions including benign prostatic hyperplasia, inflammation and age have diminished effect on IsoPSA results
• Measures all PSA isoforms without an a priori requirement of knowing which species are present, instead of just three or four prescribed antigen forms as measured by currently available tests

Series of firsts

IsoPSA represents the first potentially cancer-specific biomarker for prostate cancer detection and prognostication, Dr. Klein points out. Development of the assay has been ongoing for several years, and the most recent clinical test represents its world’s first clinical evaluation.

Most recently, the European Urology study demonstrated for the first time that use of a structure-based assay—rather than a concentration-based test—for the PSA has better diagnostic accuracy for detecting cancer and grade.

“Results of this study suggest that if validated and adopted clinically, IsoPSA could significantly reduce the number of unnecessary biopsies while preserving both positive and negative predictive values for cancer detection and staging,” says Dr. Klein. “This would be a major advancement in our ability to provide men with the information they need to make informed decisions about their care.”

*Cleveland Clinic has an equity position in Cleveland Diagnostics. Dr. Klein has no direct or indirect personal financial interests in the company.