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New Biomarker Holds Promise to Discriminate Between High-Grade and Low-Grade Prostate Cancer

July 2016, Vol 7, No 6

When combined with other clinically relevant parameters, a novel protein biomarker called IsoPSA can improve selection of patients with prostate cancer for biopsy. IsoPSA holds promise for improved diagnostic accuracy, said Eric A. Klein, MD, Chairman, Glickman Urological and Kidney Institute, Cleveland Clinic, OH, at the 2016 American Urological Association annual meeting.

In an ongoing multinational study comparing the clinical performance of IsoPSA with serum prostate-specific antigen (PSA) measurement, “using Iso­PSA reduced unnecessary biopsies by 52%, missed no high-grade cancers, and correctly identified 97% of low-risk patients,” said Dr Klein.

To be clinically useful, a biomarker must be specific to tissue type and to cancer. PSA is prostate-specific but not prostate cancer–specific, which limits its ability to distinguish between prostate cancer, prostatitis, benign prostatic hyperplasia, and urinary tract infection accurately, Dr Klein explained.

The diagnostic accuracy, predictive value, and clinical utility of current biomarkers are limited by a lack of cancer specificity and by relatively poor sensitivity.

PSA has multiple structural isoforms that can be detected in the serum and that are cancer-specific. Current screening assays measure only the concentration of a limited number of prespecified isoforms. By contrast, IsoPSA measures the concentration of all isoforms. “That’s important, because in different patients there may be different PSA isoforms that are associated with cancer that are not detectable by the current assays,” Dr Klein said. “Furthermore, there may be different isoforms of PSA in the same patient over the course of time that are also not captured by current assays.”

IsoPSA is a novel assay that uses aqueous-based solvents to detect overall changes in the structure or isoform mixtures of biomarkers.

The IsoPSA assay interrogates the entire PSA isoform distribution in serum, as opposed to preselecting individual protein biomarkers. “This is an add-on to standard total PSA/free PSA assays; it’s done very cheaply without requiring an additional blood draw,” said Dr Klein. “The way it will be reported…is the percent likelihood for an individual patient for the presence of Gleason 7 cancer.”

Preliminary studies showed excellent discrimination between cancerous and benign prostate diseases.

Dr Klein’s study included 132 patients with PSA values of 2 ng/mL to 26 ng/mL. The objective was to assess the clinical performance (ability to predict for Gleason 7 cancer) of Iso­PSA against PSA with 12-core ultrasound-guided prostate biopsy. Compared with PSA alone, which had an area under the curve (AUC) of 0.61 for prediction of Gleason grade ≥7 cancer, adding IsoPSA to the model improved the AUC to 0.85.

The positive predictive value for aggressive cancer was very high, and the negative predictive value (negligible chance for aggressive cancer) was also very high, said Dr Klein.

In patients at very low risk for aggressive disease, the negative predictive value was 97%; in those at high risk for high-grade disease, the positive predictive value was 86%.

“So IsoPSA has a very high ability to correctly discriminate clinical outcome,” Dr Klein said.

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