The Role of Liquid Biomarker for Early Detection of Prostate Cancer - Episode 6

Algorithms for Diagnostic Testing in Prostate Cancer

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Key opinion leaders in urology review factors to consider when selecting screening and risk-assessment tests for the diagnosis of prostate cancer including insurance coverage, commercial availability, and patient preference.

David Albala, MD: I am trying to get a practical little algorithm developed for the audience. Obviously, almost everybody around the country does PSA [prostate cancer antigen] testing in some form, maybe regular to total PSA or free to total PSA or looks at PSA velocity. Then would you go to the blood test, or would you go to the urine-based test? I am curious on how you put that together and then I will tell you what my algorithm is, and we'll see if we're similar.

Judd W. Moul, MD: Sure. There may be patients who only get a PSA and a rectal exam. For example, a patient with a PSA more than 20 and an abnormal digital rectal exam.

David Albala, MD: Fair enough.

Judd W. Moul, MD: We need a biopsy. We have been seeing quite a number of those guys seem more as we have gone through COVID. I do not know if it is just more or the fact that this primary care initiative that we have has just been bringing these guys out of the woodworks.

David Albala, MD: Or maybe the after-effects as well of the task force were stuck. Several papers have shown that when prostate screening and PSA testing got a de-rating, we started to see an uptake in metastatic disease then they reduced it to a C rating a couple of years later. I do not think we have caught up completely. You are exactly right. I think that patient that has a PSA of 20 or you find an abnormality on the rectal exam, that is a no-brainer. We are going to biopsy those guys and that's the standard of care. Let us take a guy that comes in, his PSA is abnormal, maybe it's between 4 and 10, you don't feel anything which is many of the patients that we examine. How do you work that patient up and what do you do? Do you do the urine-based test first or do you do the blood test?

Judd W. Moul, MD: First, as a urologist, I do the rectal exam. That is my first step when I'm seeing a patient because I really want to contextualize the PSA based on the size of the prostate. Rectal exams, we all know, are not perfect, and it is hard to teach a primary care physician to do a rectal exam and many of them are not that interested. But we as urologists and as urology educators, we need to make sure all our residents who we train know how to do a good rectal exam and size of prostate. If I have a gentleman who has a very robust prostate, significant BPH on DRE, and it's a smooth DRE with no nodules, sometimes I may just only do the PSA test and reassure that gentleman and schedule him back in a year. Just important to point out that the basics of what we do as urology is still there. However, if it is a borderline on rectal exam, if the patient has a borderline PSA family history, our next test usually is going to be a prostate health index and those are going to be binned in four groups. Generally, if the patient is low risk on pHi then they're going to be reassured and maybe come back in six to 12 months. If it is a high-risk pHi with a 50% greater probability of prostate cancer most of the time, we will recommend a biopsy without necessarily going to the exosome. However, as you said, sophisticated patients, many patients are reluctant, and they want more data. In those patients who want more data we will get the exosome and then if they have a combination of high-risk pHi and exosome greater than 15.6, we are going to really push for a biopsy. If the patient still does not want a biopsy and insists on an MRI, we will order the MRI counseling the patient that he might have to pay out of pocket. Where the exosome has helped me, the most is in patients who have that intermediate prostate health index – the gray zone. There is a gray zone there too. Then I like to get the exosome. Or the patient who is just reluctant and just has a no show and I am the third urologist telling him he needs a biopsy. Sometimes I am using the exosome test to try to convince him that he has a condition that needs to be taken seriously. I use it to try to increase compliance as much as anything. Also, finally I will say, our practice is employing more physician extenders, APPs. We train them the best we can, but they are not urologists, they have not been in practice 30 years like I have. Sometimes our younger APPs are using these tests because they are not quite as confident with a rectal exam. Is that right or wrong? It is a reality of needing some of those tests in our current workforce.

David Albala, MD: I think that is terrific. We up here have adopted obviously using PSA as our primary test, much like what I did when I was at Duke. We did go to a blood test with the 4K score and then we pivoted a little bit to the urine studies. It started with SelectMDx and now, I think, with exosome, having the home kit – a couple of things. One is, for exosomes they must be over the age of 50 to do the test. Most of our patients, when they come into the urology clinic leave a urine specimen so it is hard to get them to urinate again. Then I just say, "We're going to mail this to you," and it works out well. That has been my test. When they get the exosome test, as you say, if they are hesitant about a biopsy, that is where the MRI, to me, fits in place. If the patients are concerned, then we go directly to a biopsy. I think the algorithms can be massaged depending on the area where you are and the tests that are readily available. We don't have pHi up here, so we relied on the K, which is commercially available, and it was a good starter test.

Judd W. Moul, MD: Dave, I do not have a lot of experience or any experience with the Select urine test. What is the difference or what has been your experience when you look at those two?

David Albala, MD: They're very comparable tests. With the Select test, you do need to do a rectal massage, so it is almost like a PCA 3 test. Maybe it is a PCA 3 on steroids, so to speak, because you do have to do a rectal exam in these patients. But when you looked at the areas under the curve and the accuracy of the test it appeared to be a little bit better than some of the blood tests and so that's why we initially pivoted a little bit to the urine test and then when exosome came out, just the ease for the physician made it a little bit easier to do. When a new test comes out, I look at the efficacy, I look at the cost, I look at the side effect profile, I look at the ease of doing the test and then the durability. Those five things, whether it's a new drug, a new procedure, or whatever, I always think of those five things in the back of my head to try to put these tests in perspective. Because when they come out, there is a lot of hype, there's a lot of excitement about these new tests, you want to bring them back down to earth and put them in their place on where they really have a place. That is how I've used things and it's served me pretty well.

Transcript edited for clarity.