Solvent Interaction Analysis of PSA Reduces Need for Biopsies

A novel test for serum levels of prostate specific antigen (PSA) was found to be better than currently available assays in distinguishing cancer from benign conditions, and identifying patients with high-risk disease.

The IsoPSA test was developed at the Cleveland Clinic. This method is designed to evaluate the changes to the structure of the PSA protein biomarker. These structural changes directly relate to cancer mutations. In contrast to looking at gene mutations, this technology provides direct information about the onset or progression of the disease, not just predicting risk of getting it.

IsoPSA is based on the principle of solvent interaction analysis (SIA). The basis of SIA is the separation of proteins with distinct physiochemical properties by a biphasic system. Two distinct immiscible solvent systems arise when polymers and salts are mixed in water. A sample is first placed in the aqueous two-phase system. The system is agitated and then centrifuged to thoroughly mix and then separate the solutes. All protein isoforms partition unequally between the top and bottom phases based on their structure and interaction with other proteins.

SIA technology reports a quantitative ratiometric parameter that is independent of the absolute expression level, called K, which represents the ratio of the biomarker concentration in a customized biphasic solution. The value of K is used as standard cut-off clinical parameters once calibrated against known clinical samples. The biomarker concentration in each of the two phases is measured with a simple conventional technology such as ELISA, which can detect the biomarker but is incapable of detecting changes to its structure.

The investigators used IsoPSA to conduct a multicenter prospective study of 261 men scheduled for prostate biopsy at five academic and community centers in the United States enrolled between August 2015 and December 2016. Results revealed that IsoPSA demonstrated a 48% reduction in false-positive biopsies; at a cutoff selected to identity men at low risk of high-grade disease, there was a 45% reduction in the false-positive rate. The IsoPSA assay outperformed traditional prostate-specific antigen detection in predicting the overall risk of prostate cancer and the risk of clinically significant cancer in this preliminary study. The IsoPSA assay could assist in determining the need for prostate biopsy for patients.

"Despite criticism, PSA has transformed the landscape of early detection, screening, and management of prostate cancer in the last few decades," said first author Dr. Eric Klein, chairman of the Glickman Urological & Kidney Institute at the Cleveland Clinic. "Unfortunately, PSA is tissue-specific but not cancer-specific, leading to over diagnosis and over treatment of biologically insignificant cancers, which is widely recognized as a key limitation in its clinical utility. The methodology used in the IsoPSA assay represents a significant departure from conventional ways to define biomarkers in blood, and may be applicable to improving other cancer biomarkers."

The study was published in the April 7, 2017, online edition of the journal European Urology.