The IsoPSA biomarker displays superior diagnostic accuracy in the early detection of prostate cancer, thereby helping to avoid unnecessary prostate biopsies.


There is a growing population of patients with prostate cancer who should be monitored rather than immediately treated or subjected to initial or repeat biopsy, according to Jason M. Hafron, MD.

“It is estimated that in the United States, $4 billion is spent annually on unnecessary prostate biopsies,” Dr. Hafron says. “While we know that maximizing early detection increases the detection of both indolent and aggressive prostate cancers, it may lead to unnecessary biopsies.”

To address this, the National Comprehensive Cancer Network’s (NCCN) Prostate Cancer Early Detection guidelines panel recently added IsoPSA—a blood-based, structure-focused assay for high-grade prostate cancer—to a list of biomarkers that may aid in the detection of early malignancies. “This can be helpful for patients who have a high PSA and/or suspicious digital rectal examination findings pre-biopsy,” Dr. Hafron notes.

Prevalence of High-Grade Prostate Cancer was 35.3%

For an investigation published in Urologic Oncology, Dr. Hafron and colleagues conducted a validation trial to determine the performance characteristics of IsoPSA in detecting high-grade prostate cancer versus low-grade and benign conditions. Blood samples were collected from patients with serum PSA between 4 and 100 ng/ml at multiple clinical sites within the 30 days leading up to a prostate biopsy. The prevalence of high-grade prostate cancer was 35.3% in the study group.

“In addition, we looked at the test’s ability to detect any cancer versus benign conditions of the prostate,” Dr. Hafron says. “The test parameter (IsoPSA Index) was evaluated by receiver operating characteristic (ROC) analysis in comparison to total PSA and percentage of free PSA.”

IsoPSA May Reduce Prostate Cancer Biopsies by 55%

Several key findings from the clinical validation study stand out, according to the researchers. “Using specificity as a marker, we estimate that IsoPSA would prevent 47% of biopsies compared with 21% and 14% for PSA and percentage of free PSA, respectively, in low-risk subjects,” he says. “This estimate has been borne out by a large, real-world, clinical utility study, which suggests that IsoPSA could reduce biopsies by 55%.”

The test performed similarly among patients who had not yet had a biopsy and those that had a pervious negative biopsy, Dr. Hafron notes. “The test results were not affected by 5-ARIs or alpha blockers, two classes of drugs frequently taken by patients suffering from benign prostatic hyperplasia (BPH). This is important, as other tests cannot be used in patients taking these drugs.”

IsoPSA was shown to have dramatically improved specificity versus PSA and percentage free PSA, without loss in sensitivity. Dr. Hafron says this implies that false-positive results will be reduced dramatically, while missing no, or few, additional true cancers.

IsoPSA May Also Be Helpful for Early Detection of Other Cancers

“Our study validates the diagnostic accuracy of the IsoPSA test, concluding that it displays superior diagnostic accuracy of total PSA and percentage-free PSA in assessing the risk for high-grade prostate cancer,” Dr. Hafron says. “Clinical use of IsoPSA may result in a significant reduction in unneeded biopsies for low-risk patients. As mentioned previously, IsoPSA also displays clinical utility in patients with symptomatic BPH on standard medication regimens.”

The NCCN’s recent recommendation to include IsoPSA in Prostate Cancer Early Detection guidelines points to how IsoPSA could change the way in which prostate cancer is diagnosed and subsequently treated, the study team concurs.

“The test’s use in active surveillance and for screening purposes is currently being evaluated,” he adds. “Moreover, the underlying technology platform, which essentially serves as a protein filter, may be helpful for breast and lung cancers as well.”