New Confirmatory IsoPSA Test Put on Fast-Track

Cleveland Diagnostics, Inc. announced that its IsoPSA prostate cancer diagnostic test was granted Breakthrough Device Designation by the U.S. Food and Drug Administration (FDA). This program is “for certain medical devices and device-led combination products that provide more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.”¹

So, what does this mean? It means that the manufacturer gets to work more directly with FDA experts to address issues and get feedback, as well as receive expedited review. The hope is to get worthy products through the approval process more quickly.

Why a new test?

A good place to start is to examine what is lacking in the current prostate cancer testing. Don’t get me wrong, I’m a big fan of the PSA test and believe the early detection of PCa it has made possible has saved countless lives. As noted in an article on the new test: “The prostate specific antigen (PSA) has arguably been one of the most successful biomarkers in medical history -- defining screening, early detection and surveillance paradigms for prostate cancer for a generation of physicians worldwide.”²

That said, while the PSA antigen is specific to the prostate, it is not specific to cancer. Other conditions, such as benign prostatic hyperplasia can cause an elevation in this marker. In addition, the test cannot differentiate levels of cancer aggressiveness. This test has come under increased criticism for leading to unnecessary biopsies and over-diagnosis and treatment of low-grade cancers.³

Improvements in prostate cancer testing

Luckily, rather than simply engage in arguments over the use of the PSA test, there are researchers looking to improve the testing arrays. In the announcement for the Breakthrough Device Designation, Dr. Mark Stovsky, the Chief Medical Officer for the manufacturer and a urologist at the Cleveland Clinic notes: “the relatively poor diagnostic accuracy and predictive value” of the PSA and states “We believe that IsoPSA has the potential to fill a major void in this space.”⁴

What is IsoPSA?

The short answer is that IsoPSA has been shown to be superior to traditional tests, such as PSA, total PSA, and percent free PSA, in predicting high-grade prostate cancer. As such, it has the potential to substantially reduce the number of unnecessary biopsies.

Now for the longer answer: the IsoPSA is what is known as a conformational test. As opposed to simply looking at the concentrations of PSA, like the standard test, the IsoPSA looks at changes in the PSA protein. Trying to keep the technical to a minimum, cancer cells have altered metabolism -- causing them to divide extra fast. These alterations also modify the cancer-related proteins, in this case, the PSA (you don’t even want me to get started on the types of alterations).

Other conformational PSA tests have improved diagnostic accuracy, but they are limited by the fact that conformational changes vary across time and by patient, and these tests can only detect a few PSA isoforms out of many. IsoPSA is the first test that can examine a blood sample across the entire spectrum of isoforms (don’t ask how, or this will get even more complicated than it already is, but feel free to check out the source article).⁵

What do the studies say?

One validation study looked at 271 men who had the IsoPSA test within 30 days of a biopsy. The test found Gleason 7 or higher PCa 94 percent of the time. Just as important, the study found that if a person had a low IsoPSA, there was a 93-percent certainty that they did not have high-grade PCa. With this level of confidence, 43 percent of biopsies could have been avoided according to the study authors.⁶

What are the better test options?

Reducing unnecessary biopsies and early detection of high-grade cancer certainly is a great step forward. One question on implementation will be whether, even with 93-percent certainty of no high-grade cancer, doctors and patients are willing to take the risk that they are not in the small percentage who will have high-grade PCA and forego the biopsy. Of course, they can closely monitor the blood work to ease the mind some on that front. In addition, it should be noted that no test is perfect and 93 percent is a far cry from having no idea about the likelihood of high-grade cancer pre-biopsy.

What took this so long?

A couple more questions are: what took so long for the Breakthrough Device Designation, and what is taking so long for approval? The studies were conducted in 2017 and 2018, and the results I mentioned above were published in early 2018. The IsoPSA is a simple blood test, which actually has the potential to greatly reduce invasive procedures and overtreatment. If there was ever a medical procedure ripe for fast-tracking this may be it, and yet even the expedited process seems pretty drawn-out.

Don’t get me wrong, I’m all for due diligence and patient safety when it comes to medical approvals. But in this case, the scales of medical prudence seem tilted against the interest of patients, particularly when so much of the medical community is turning against the standard PSA test. Hopefully, this more precise test will be available to men in need soon.