Prostate cancer affects roughly 1 in 9 American men in their lifetime, with 174,650 new cases reported each year. However, current prostate specific antigen (PSA) tests lack specificity, leading to overdiagnosis and overtreatment of inconsequential cancers. Cleveland Diagnostics Inc. is looking to change that with its IsoPSA assay, which just received a breakthrough device designation from the U.S. FDA. In clinical studies, the noninvasive, blood-based test has been shown to have higher accuracy than standard PSA tests.
To improve cancer diagnosis, the clinical-stage liquid biopsy startup has developed a proprietary solvent interaction analysis (SIA) technology, which assesses structural changes in the PSA protein biomarker for prostate cancer rather than overall concentration of PSA in prostate tissue, which is what traditional tests do. That provides doctors with clues about onset and progression, not just a patient's risk of getting the disease. A key drawback of current PSA tests is their failure to differentiate advanced or higher-grade cancers that require immediate treatment from less concerning PSA levels. This can lead to overdiagnosis and unnecessary surgical biopsies to determine if additional tests, such as CT or bone scans, are needed.
"The clinical utility of PSA is limited by the relatively poor diagnostic accuracy and predictive value of the test," said Mark Stovsky, chief medical officer at Cleveland Diagnostics and a staff urologist at the Cleveland Clinic Foundation. "Clinicians today are using an array of diagnostic tests and procedures to inform decisions about a patient's prostate health and the risk of prostate cancer. We believe that IsoPSA has the potential to fill a major void in this space."
In May, Cleveland Diagnostics announced the publication of results from a multicenter, prospective validation study of IsoPSA in the Journal of Urology. The study, led by investigators at the Cleveland Clinic, assessed IsoPSA's ability to detect high-grade prostate cancer (Gleason 7 or greater) in blood samples drawn from 271 men who were scheduled for prostate biopsy. The assay's discriminatory prowess was validated by ROC analysis and compared with earlier test results. Performance also was validated through comparison with multiparametric MRI-ultrasound vs. transrectal ultrasound guided biopsies.
The results showed the IsoPSA's accuracy to be superior to PSA, the current gold standard in prostate cancer detection. Specifically, the assay AUC (area under the curve) was 0.784 for high-grade vs. low-grade cancer or benign tissue, compared with 0.657 with total PSA studies. Specificity of IsoPSA was also higher, at 40% vs. 22% for total PSA.
"If 1,000 patients were biopsied, the assay would have reduced the number of unnecessary biopsies from 705 to 402 (43%) with only 22 missed high-grade cancers, of which [seven] would have been Gleason sum 4 + 3 or higher," the authors wrote. "Subset analysis of multiparametric magnetic resonance imaging guided biopsy produced a substantial improvement of the AUC to 0.831." An earlier study published in European Urology produced similar results.
45% fewer biopsies
Cleveland Diagnostics estimates that its liquid biopsy test could cut the number of unnecessary surgical biopsies by 45%, or 500,000 procedures, sparing patients undue risk and pain and saving $1 billion in health care costs annually.
"We are grateful that FDA recognizes the potential of IsoPSA, the first test in our pipeline of simple, affordable, and highly accurate cancer tests that focus on cancer-relevant changes to protein biomarkers in blood," said Cleveland Diagnostics CEO Arnon Chait. "We look forward to working closely with FDA to expedite the appropriate approvals and get this important new test into the hands of physicians."
Chait and Boris Zaslavsky, an analytical biochemist, founded Cleveland Diagnostics in October 2013 to leverage their SIA protein structure technology in the area of cancer diagnostics. The duo previously co-founded and worked together at Analiza Inc., where the technology was developed, and later at Analizadx LLC, which focused on exploring applications for the technology. After deciding there was an unmet need in cancer detection, they approached the Cleveland Clinic Foundation for help in commercializing the technology. The company raised a total of $2.4 million in two equity rounds in 2015 and 2016.
FDA breakthrough device designation is intended to provide quicker access to novel diagnostics and treatments for life-threatening or nonreversible debilitating conditions. The agency works closely with companies on product development and preparation of regulatory submissions. Cleveland Diagnostics is aiming for an FDA greenlight for IsoPSA in 2020, according to the company's website. In addition to prostate cancer, the company is developing noninvasive diagnostics for breast cancer and Alzheimer's disease.