Eric Klein, MD, Chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic talks about the IsoPSA test as a prostate cancer biomarker.
Is prostate cancer screening important?
Dr. Klein: Prostate cancer screening is important because if it is caught early prostate cancer is easy to cure. There’s solid evidence that by using PSA-based screening strategies we save lives. A great example recently is Al Roker. African American men have the highest rate of prostate cancer and the highest death rate due to prostate cancer of any group in the world. That is probably because of the lack of access and attitudinal barriers to screening, rather than it being a more aggressive cancer in African Americans. That is probably not true. But he went public with his story after he was screened. He had early stage cancer that needed treatment and underwent successful surgery and that is a great success story. Also, there’s clear evidence that when the U.S. Preventive Services Task Force recommended against screening almost a decade ago now that rates of screening plummeted. But the number of patients who had an aggressive cancer, a locally advanced cancer and metastatic cancer went up after that. So again, there’s solid evidence that a PSA screening strategy saves lives. That is why screening is important.
Could you briefly explain what the IsoPSA test is and how it works?
Dr. Klein: PSA is a protein made by the prostate, made by normal prostate cells and it goes into the bloodstream. The amount of PSA in the bloodstream goes up when the prostate gets larger, as happens with men over 50 with prostate cancer. One of the challenges with PSA is, while it detects cancer at a time when it is curable, it does not distinguish between non-cancerous prostate enlargement and prostate cancer. It also leads us to do too many biopsies. Too many men have a biopsy who end up not having cancer and too many men end up having a biopsy that shows only low-grade cancer, which we know by and large does not need to be treated. So, IsoPSA was designed to improve our ability to detect the presence of higher-grade cancers like Al Roker had so we can identify those cancers that need treatment. IsoPSA is a new kind of assay or lab test, it is not a new kind of PSA. It is a new way of measuring the different abnormal proteins that result when cancer occurs as opposed to the normal proteins when PSA goes up because of non-cancerous prostate enlargement and it’s far more accurate than PSA in identifying the presence of a high grade cancer. So, a PSA is a little better than a coin flip in determining whether someone has a high-grade cancer where the IsoPSA gets it right about 80 percent of the time.
How does the IsoPSA test compare to conventional PSA test?
Dr. Klein: This is a simple blood test. Just like a PSA it is a simple blood draw, but it is far more accurate in detecting the presence of high-grade cancer. The real value here is that in patients who got an IsoPSA about 60 percent were able to avoid a biopsy because the IsoPSA test suggested that the rise in their normal PSA was due to non-cancerous prostate enlargement or just a little bit of low-grade cancer and we are not going to treat it anyway.
Can it detect any level of prostate cancer or only high grade?
Dr. Klein: It will detect some low-grade cancer but at a rate far less than a PSA does. So, our goal in using an IsoPSA is to avoid biopsies in men who are not likely to have a cancer that needs treatment. That is the real value and again it allows us to do that in about 60 percent of patients. So, say the next hundred patients I see have a PSA above 4, which is the usual cutoff for recommending a biopsy. If we add IsoPSA, instead of doing 100 biopsies we will end up only doing 40 biopsies. So that avoids the inconvenience, cost, discomfort, and minimal complication rate in 60 people who are really, really unlikely to have a high-grade cancer and it allows us to biopsy those patients where the biopsy is likely to be informative about something important for their health.
Talk about the different kind of studies that you were involved in.
Dr. Klein: There are two studies published about IsoPSA. One was about the initial experience so we could determine who needs to be scheduled for a prostate biopsy. These are men who met standard clinical criteria for having a biopsy with an elevated PSA level. Some of them had low-grade cancer already and were on active surveillance. Some had a bump on the prostate that felt like cancer. But the standard clinical criteria were a little over 200 men to determine whether IsoPSA, a simple blood draw before the biopsy, could predict the presence of high-grade cancer. The second study was similarly designed with several hundred more patients scheduled for a biopsy for the standard clinical reasons and had a blood draw beforehand. That was a validation study. Based on the data that we saw in the first study; we got a sense of what the accuracy was. The lab test was refined to be sure the results were reproducible. Then we took a larger population of patients and did a validation study where we retested the same test which was optimized to see if we could get the same results. The results of both studies were remarkably similar. IsoPSA was able to predict the presence of high-grade cancer with about 80 percent accuracy.
How does the IsoPSA test prevent biopsies and how many annually do you think it could prevent?
Dr. Klein: A substantial number. IsoPSA prevents us from doing prostate biopsies in some men because it does a better job of distinguishing whether the elevation in PSA is due to non-cancerous prostate enlargement or due to high grade prostate cancer. We do not want to biopsy men who do not have cancer because there is no reason to do that. We do not want to biopsy men who have low-grade cancer because we are not going to treat that anyway. We would be better off, and men would be better off not being diagnosed with it. The way it reduces biopsies is to focus the biopsies only on those men who are at highest risk. There are around 1.3 million prostate biopsies done in the United States every year. So if our initial experience in a very small number of patients, about 200, can show that we can avoid biopsy in about 60 percent of men who would normally be recommended for a biopsy, that’s a pretty substantial reduction in the number of biopsies. Maybe several hundred thousand.
Has this test been approved and is it available to patients?
Dr. Klein: The test has not been approved by the FDA yet. Cleveland Diagnostics, the company that developed the test is preparing an application to be submitted to the FDA in the first quarter of 2021 for approval. It is now available in certain markets in the United States for what is called a lab developed test with an out-of-pocket cost for the patient. Eventually, if the FDA approves the test or insurers are convinced of its value, it is likely it will have insurance coverage. But that is a regulatory and commercialization process that takes time.
What is the target demographic of the IsoPSA test and what are the signs that patients should have it done?
Dr. Klein: IsoPSA is indicated for all men who have a regular PSA test. The standard recommendation is to have a baseline PSA at age 50 and to be tested at repeated intervals over the course of your lifetime depending upon what your initial PSA level is and what your risk factors are. So if you have average risk, meaning no family history and you’re not African-American, a baseline PSA at age 50, if it’s below about .7, you probably can be screened every two or three years for several years. If you have risk factors such as a positive family history, brothers, a father, people close to you in the bloodline with prostate cancer, you probably ought to be screened every year. Or if you are a BRCA carrier or have BRCA in your family, those men are at increased risk of prostate cancer. They should be tested every year. IsoPSA is indicated for any man who has a PSA that the physician feels would perhaps warrant a biopsy and to distinguish whether the PSA elevation is due to non-cancerous prostate enlargement or whether there’s actually a cancer that needs treatment. That is who should have an IsoPSA. So not every man who gets a PSA should have an IsoPSA. If your PSA is below 4 or is not worrisome for cancer, there is no reason to do an IsoPSA. But if your PSA is worrisome for the presence of cancer, then an IsoPSA can help distinguish whether it really is cancer or whether it is non-cancerous prostate enlargement.
What does this mean for the future of clinical practice and for patients both physically and financially?
Dr. Klein: This could have a real impact on clinical practice. If we can reduce the number of biopsies that we do, that is a boon for everyone who avoids a biopsy. It is reassurance that they do not have prostate cancer and it avoids the cost and complications. Although the complication rate from a biopsy is low, there is about 1/2 percent risk of a serious infection. So, all those savings and if we could reduce the 1.3 million biopsies a year by 50 or 60 percent, that would be a huge savings. In terms of cost, it is still to be seen whether the savings from avoiding 60 percent of biopsies is worth the added cost of the test. That is something Cleveland Diagnostics will have to discuss with the insurance companies and come to a reasonable estimation of what is a reasonable cost for this test due to avoiding all the biopsies and downstream effects of those biopsies. Big picture, when you do the cost benefit analysis, it will be greatly beneficial to use an IsoPSA to help decide on a biopsy because it avoids so many biopsies.
How will this add to the diagnostic toolkit for clinicians?
Dr. Klein: PSA has shown real value. We know when men are screened with PSA, we save lives. We prevent men from dying from prostate cancer. The cost of doing it is a lot of men get a biopsy that does not show cancer or shows only low-grade cancer. So, the IsoPSA adds to the toolbox because it allows us to more accurately identify men at highest risk for high-grade cancers and only do biopsies in those patients and avoid biopsies in patients who don’t need a biopsy and that’s a good thing.
Interview conducted by Ivanhoe Broadcast News in November 2020.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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