May 20, 2022/Cancer

Real-World Study Supports IsoPSA as a Prostate Cancer Biomarker

Reflex testing led to substantially fewer provider recommendations for prostate biopsy and MRI

Results of a new study show that IsoPSA®, a novel prostate cancer test, is readily adopted by practitioners in various practice settings and its use significantly reduces biopsies in men being evaluated for elevated prostate-specific antigen (PSA).


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Performed by Cleveland Clinic researchers, the observational study is the first to evaluate provider behavior using IsoPSA in a real-world clinical setting. The tool previously was validated in a large, prospective, multicenter trial, which showed that it reduced costs when compared with use of PSA and percent free PSA.

“Having the information from IsoPSA allowed providers to recommend prostate biopsy far less frequently than they would have before, and that was not affected by their training or experience,” says study co-author and urologic oncologist Robert Abouassaly, MD. “This suggests that the tool is easy to use and interpret and provides useful information in all clinical settings.”

These findings supported the addition of the IsoPSA test to the National Comprehensive Cancer Network Prostate Cancer guidelines for early detection of the disease.

Study at a glance

The participants in the observational research were 38 providers – advanced practice providers, fellowship-trained oncologists and general urologists – practicing in community and academic locations that were part of the Cleveland Clinic health system. Nine hundred of their patients were being evaluated for prostate cancer, 734 of whom were eligible for IsoPSA testing.

Criteria for use of IsoPSA were age ≥ 50 years, total serum PSA ≥ 4 and < 100 ng/mL and no history of prostate cancer. The providers used a standard template to document their biopsy recommendations for the patients before and after IsoPSA testing. The primary outcome was the number of recommendations for biopsy and magnetic resonance imaging (MRI) that changed after the IsoPSA testing.

The authors found that IsoPSA testing resulted in a 55% net decrease in recommendations for prostate biopsy in men with total PSA ≥ 4 ng/mL and a 9% decrease in recommendations for MRI. The IsoPSA results strongly correlated with provider recommendations for prostate biopsy. Biopsy was recommended for 87% of patients with an IsoPSA index above the threshold and it was not recommended for 92% of patients with an IsoPSA index below the threshold.

Says Dr. Abouassaly, “Our previous clinical validation study estimated a 43% reduction in unnecessary biopsies with IsoPSA. What we found in this study is that it’s likely to be even higher in general practice. The reduction in MRI was more modest.”

Origins of IsoPSA

Developed by Cleveland Diagnostics, Inc.* in partnership with the Glickman Urological & Kidney Institute, IsoPSA received breakthrough device designation from the U.S. Food and Drug Administration (FDA) in late 2019. It is designed to stratify risk of biologically significant prostate cancer (Gleason grade ≥ 7) and intended to be used in men aged 50 and older with a total PSA ≥ 4 ng/mL who have not been diagnosed with prostate cancer and are not under active surveillance.


Unlike PSA testing, which is tissue-specific and prone to overdiagnosis of low-grade cancers and over-treatment of low-mortality tumors, IsoPSA is a reflex test. It overcomes the shortcomings of PSA by taking a different biological approach. Rather than assessing PSA concentration, it interrogates a patient’s serum sample for broader, structural changes in PSA levels as a result of disease pathogenesis.

Statistical analysis results with IsoPSA in the validation study showed that with all assays set at 93% sensitivity, the tool outperformed conventional PSA tests – total PSA [tPSA], free PSA [fPSA], and combined tPSA and fPSA – in detecting clinically significant cancers. IsoPSA’s positive predictive value was 43%, compared with 35% for tPSA, 32% for fPSA and 37% for tPSA plus fPSA.

In the observational study, use of IsoPSA also resulted in 20 biopsies in patients for whom providers previously had not recommended them. Six additional high-grade and 2 additional low-grade cancers were detected. In 9 other patients, no cancer was found on biopsy; no biopsy findings were available for the remaining 3 patients.

Future research

Cleveland Clinic researchers believe that IsoPSA has potential to help patients avoid the discomfort and potential complications of biopsy, reduce over-detection of indolent prostate cancer, and reduce healthcare costs. The next step in their evaluation of the tool is to evaluate the impact of clinical factors, such as previous MRI or PSA density information, on provider recommendations for patients with elevated PSA. Says Dr. Abouassaly, “In recent years, more and more men have undergone MRI testing, and adjusting for that and other factors, such as family history of prostate cancer, in future studies of IsoPSA will be important.”

*Cleveland Clinic Innovations has an equity position in Cleveland Diagnostics.


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