BackTable / Urology / Podcast / Transcript #112

Podcast Transcript: Preliminary Complementary Data for Pairing mpMRI and the ExoDx Prostate Test

with Dr. David Albala

This week on BackTable Urology, Dr. David Albala, chief of urology at Crouse Hospital, and Dr. Jose Silva discuss the benefits and integration of biomarkers in prostate cancer diagnosis. You can read the full transcript below and listen to this episode here on BackTable.com.

The Evolution of Prostate Cancer Screening

Identifying Risk Factors for Prostate Cancer

Approaching an Elevated PSA Level

Interpreting ExosomeDx Scores in Clinical Practice

Clinical Decision-Making with Elevated Biomarkers

The Future of Urology: Personalized Approaches to Prostate Cancer Screening & Care

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Preliminary Complementary Data for Pairing mpMRI and the ExoDx Prostate Test with Dr. David Albala on the BackTable Urology Podcast)

Ep 112 Preliminary Complementary Data for Pairing mpMRI and the ExoDx Prostate Test with Dr. David Albala

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This is Dr. Silva [unintelligible 00:02:31] host this week, and I'm happy to introduce our guest, Dr. David Albala. He completed his medical school training at Michigan State University, and went on to complete his surgical residency at the Dartmouth-Hitchcock Medical Center. Following this, Dr. Albala went on to do a fellowship in endourology at Washington University Medical Center in St. Louis, Missouri, under the direction of Ralph V Clayman. At Washington University, he was part of the team that performed the first laparoscopic nephrectomy in humans. That's very good accomplishment.

[Dr. David Albala]:
Thank you.

[Dr. Jose Silva]:
Currently, he's on the board of directors of the Large Urology Group Practice Association or LUGPA. He is chief of urology at Crouse Hospital in Syracuse, New York. Dr. Abala Dave, welcome to BackTable.

[Dr. David Albala]:
Thanks so much for having me. It's a pleasure to be here.

The Evolution of Prostate Cancer Screening

[Dr. Jose Silva]:
Perfect. Today we're going to talk about prostate cancer screening and genomic testing. Can you walk us through your path in terms of prostate cancer screening? I know that there's been changes in the guidelines over the years. Can you walk us through since your early days in residency up to this point?

[Dr. David Albala]:
Sure. Thanks for, again, having me, Dr. Jose Silva. Prostate cancer is really an interesting disease state to study. Over the years we've learned so much and things have changed dramatically. When I first started my training, people would come in with advanced prostate cancer. That's right when PSA was being brought into the marketplace and the United States FDA approved it for prostate cancer screening back in the 1980s. We used this blood test, it was a simple blood test, relatively inexpensive, that could be done on everybody that walked through the door, and we started to diagnose more and more men with prostate cancer.

What was really interesting is that as PSA testing became more popular, we actually started to see you know more patients getting treated, and the disease, the number of patients that were dying was starting to drop off. You might say that PSA was a great test, it still is a great test that's used, and really is the first test that we use to screen patients for prostate cancer. Over time, what we started to see is that as we understood prostate cancer more, there's a group of patients that have prostate cancer that may be indolent. The disease grows very, very slowly.

These patients you know were diagnosed with prostate cancer and perhaps some of them didn't even need to be treated. We saw this mortality starting to decrease, but we also saw that we were starting to perhaps over-treat a number of patients. You weigh both sides of the penny if you will, the advantage of diagnosing men with prostate cancer, but also treating patients perhaps didn't need to get treated for prostate cancer. That continued on in the early 2000. Then the United States Preventative Task Force in 2012 really came out with a controversial decision.

That decision was that PSA testing may not have any value. They looked at some studies and this task force essentially recommended against PSA testing. As urologists, we diagnose prostate cancer two ways, one with a digital rectal exam, secondly with a PSA test. You might say, jeez, the digital rectal exam should help us identify these patients, but if I lined 100 men up with prostate cancer and did a digital rectal exam, I would detect prostate cancer in less than 50 of those individuals. Our finger is not a great screening test, but when you combine it with the blood test, you actually then are able to make the diagnosis and make recommendations of biopsy.

The PSA test doesn't diagnose prostate cancer. It's used to give us information on if a patient has an abnormal finding or the PSA is elevated, then we would recommend patients undergo biopsies. Now a biopsy of the prostate typically has traditionally been putting a small probe, an ultrasound probe in the rectum, taking some pictures of the prostate, and then randomly biopsying different areas within the prostate. It's a random biopsy. Then over the years, we then have started to use different tools, and in particular, MRI has come into the forefront in which we can get a lot of good clinical information from an MRI.

It's much more sensitive in picking up these cancers that may be more aggressive. Using MRI techniques or an MRI fusion biopsy, we can actually target an abnormal area within the prostate. Once the task force came out with this recommendation, all of a sudden we started to see our prostate cancer death rates start to increase because we were detecting less cancers. The real goal of PSA was to identify these individuals at an earlier stage and such that we could recommend different treatments. The United States Task Force then re-looked at this data, went from a D rating, which essentially says do not do the test, to a C rating.

That brought into the era of what we call shared decision-making. When a physician meets with a patient, you sit down and talk about risk factors. With prostate cancer there's a variety of risk factors. Age is one risk factor. Race. If you're African American, you have a much higher incidence of prostate cancer. Family history. If your brother or your father, you have a two to threefold increase risk of prostate cancer. Genetic markers. BRCA testing, BRCA1 and BRCA2. If you have these types of mutations, you do have potentially a higher risk of prostate cancer.

Other clinical factors. Diet has been studied, chemical exposure has been studied, maybe less so than you know age, race, or family history, or genetic mutations. Combining all this data, what we want to try to do today in 2013 is identify those patients that have risk factors, do appropriate biopsies, not do biopsies that aren't appropriate in individuals. The PSA test has evolved. We used to use a cutoff of 4. If you had a PSA less than 4 when I trained, the likelihood of prostate cancer was low. If it was above 4, the increased risk of prostate cancer existed.

We then used markers like PSA density, comparing it to the volume of the prostate, the PSA reading. We then developed what we call age-specific PSA ranges. An individual that, say, 40 years old, his PSA, a normal PSA should be 2.5 or less. If you compare that to a 75-year-old man, his normal PSA is up to 6.5. The one shoe doesn't fit every single patient. Over the years, we've learned a significant amount of information about PSA, but we've also learned that it's not the ideal test. It's not a cancer-specific test. We have to combine clinical data. Then, recently, we started to see the use of biomarkers come into helping us identify patients that are these higher-risk patient populations. We can use a variety of biomarkers, not only in the blood, but in the urine, to try to identify patients that have a high risk of prostate cancer. There's been this tremendous evolution. When I first finished my residency, if you were 40 years old and you had a family history of prostate cancer, or you were African American, that's when you got a PSA and a digital rectal exam. Then if you were 45, any individual Caucasian, no family history, those are when men got screened.

Over the years, what we've seen is perhaps we've over-screened patients, and trying to identify patients with prostate cancer. The United States Preventative Task Force made urologists look and say, maybe we should re-look at our guidelines. I think today, the current guidelines are such that if you're 40 to 45 and you have a family history, or you're African American, that's reasonable. Then, for all others, patients starting at age 55 is when these individuals should get screened for prostate cancer. Again, it's a shared decision. You come in, you get examined by your physician, and you have a discussion about this.

You make a shared decision. Then the first test that needs to be done, and our guidelines suggest this, is a routine PSA test. Once you get a PSA test, if it's elevated, you can repeat it to make sure that it's a valid test. If it is elevated, then there are a number of options. You can go right to biopsy if you want. You can do a biomarker test, a urine-based test, or a blood test, to try to pare down, maybe there's a group of these patients that have slightly elevated PSAs that you don't need to do biopsies in, that these patients don't have any risk. Then you can also integrate MRIs in that discussion as well.

[Dr. Jose Silva]:
Dave, in terms of the screening, what have you seen in your community after the message from the task force? Did you see that then primary care physicians stopped doing it?

[Dr. David Albala]:
Yes, primary care physicians in 2012, all of a sudden, stopped doing any PSA testing. Not only did they stop the PSA testing, but they also stopped doing the digital rectal exams. Now you're essentially dismantling the only effective way of identifying prostate cancer. Right after the task force made those recommendations, if you look back at the data and the mortality rates, you start to see a spike. What happens is you do PSA testing and all of a sudden the mortality drops. You stop the PSA testing, and then all of a sudden the mortality starts to increase.

There clearly is a direct relationship. There's been numerous papers published. That's why I think the United States Task Force went back and said, maybe you should discuss this with your physician. Many urologists feel that the backbone of prostate cancer is PSA and testing, and doing this testing, and we feel it should be done in appropriate patients. We also feel we should do biopsies in appropriate patients, because there is a risk with a biopsy.

Infection, bleeding, those are the biggest risk with biopsies. If we can identify those high-risk patients, perhaps we can defer biopsies in patients even if the PSA is slightly elevated. Remember one other thing that you don't have to have an elevated PSA to have prostate cancer. We see patients that have normal PSAs but are diagnosed with prostate cancer. The test is not perfect in identifying cancers in patients, and when you combine it with other things, digital rectal exam, biomarkers, MRI, you increase that sensitivity.

Identifying Risk Factors for Prostate Cancer

[Dr. Jose Silva]:
Especially, you mentioned those patients that have low PSA that have cancer. I always ask the patient if they have family members, and what I have seen, some families, uncles, brothers, they tend to have low PSAs and all of them have cancer. Definitely that family history is very important.

[Dr. David Albala]:
It's no question, and race is important. Not only is the prostate cancer more common in African Americans, but the mortality rate is higher in African Americans. When you look at Caucasians versus African Americans, you see that if you're an African American male and you develop prostate cancer, you have a much greater likelihood of dying of prostate cancer than a Caucasian.

[Dr. Jose Silva]:
Like you mentioned, usually, not only they have higher incidence of cancer, but also higher incidence of bad cancer. We're talking about high Gleasons.

[Dr. David Albala]:
Exactly. The cancers are more aggressive.

[Dr. Jose Silva]:
Dave, the other thing I want to mention, also, in terms of the guidelines, they talk about the asymptomatic patients. From my understanding, any patient regardless, we're not going to do a 20-year-old, but 43, 45, regardless of their race, if they have some symptoms, you should at least look into it, right?

[Dr. David Albala]:
No question. There are different conditions that cause symptoms in the prostate. The three big prostate diseases are BPH, which is the most common, an enlarged prostate. These men have difficulty with urination, urgency, frequency, going to the bathroom, getting up at night. In the younger population, prostatitis is the black sheep of prostate diseases, if you will, but it's extremely common in younger men. When a 25-year-old man comes in and he has burning, urgency, frequency, you have to think prostatitis and not prostate cancer.

Typically, it's rare to see prostate cancer before the age of 40. If you have some rare tumors, but it's not a disease of younger people. Prostate cancer, it's interesting that when you look and see the incidence of prostate cancer, it really increases with age. There was a study that was done that looked at the development of prostate cancer. If you're 70 to 80, you have about a 70% chance of getting prostate cancer. Now, not all of these men die of prostate cancer. Some of these diseases, this disease state is indolent. These people live in harmony with their disease.

That's really what spurred on urologists to think about doing active surveillance in men. If you're diagnosed with prostate cancer, when I first started practicing, these patients would undergo radical prostatectomies, open operations or radiation. Today, we look at the Gleason score, we try to determine how aggressive these tumors are, and based on that, we now can use genomic profiling in these patients to say, jeez, this is a tumor that is unlikely to cause a problem. The genomic markers is like, if you have two race cars, if you have a Corvette and a Volkswagen, and you know nothing about cars, you'll say the cars are going to go about the same speed.

If you lift up the hood, under the Corvette, you're going to see this gigantic engine, and you'll see a putt-putt engine in a Volkswagen, you're going to realize that the Corvette's going to go much faster. That's what these genetic studies, there's been this really blossoming of knowledge, understanding the genetics and the genomics of prostate cancer. There are tests that are available, much like what we see in breast cancer, to identify, is this an aggressive tumor? Really, what these genomic tests do is identify the wolf in sheep's clothing.

In other words, if you have a Gleason 6 disease, which is the most common Gleason score tumor that we see, usually you think that many of these patients can go on active surveillance. If you do genomic testing, and you find that the genomic test says that this is a wolf and not a sheep, those are the patients that you want to treat. We have commercially available tests, just like in breast cancer. Prostate cancer mimics breast cancer in a lot of ways, with the genomic testing, the genetic testing that's done. We're just a little behind the women. They're just a little smarter than us. The understanding in breast cancer has really blossomed.

We're now just on the tail edge of understanding genetic makeup of these tumors, and understanding BRCA genes, and so on and so forth. There's a lot to unpack in prostate cancer. The real big question is, go in, if you're at a high-risk group, you need to get screened and tested. If you're not, go in and have a discussion with your physician. Then if you do get screened and you have an elevated PSA, you need to sit down with him and decide, what's the best path for you? Should you get a biopsy? Should you do a biomarker, a urine-based biomarker, or a blood-based biomarker to determine if you should have a biopsy? Then obviously an MRI is also on the table here.

Approaching an Elevated PSA Level

[Dr. Jose Silva]:
Dave, so in your practice, what are you doing? Let's say that patient has an elevated PSA, 60-year-old PSA 5. What will be your next step?

[Dr. David Albala]:
Obviously I'll have him come in. I'll do a digital rectal examination. If the PSA all of a sudden jumped up, I might repeat the PSA to see if it's really just a spurious value. For example, men with prostatitis can have really high PSAs. I want to make sure that man doesn't have prostatitis. Usually when I do a rectal exam, I can feel a boggy or soft prostate that would suggest prostatitis.

Then here's where the fork in the road is. Should I do a biomarker or should I do an MRI to try to help me identify men at higher risk? Again, it's dealer's choice on how you want to do this. I actually think the biomarkers are really a nice way to go personally. In my practice I like to use a biomarker. There's a blood biomarker, for example, like the 4K or the Prostate Health Index. There's a number of commercially available blood tests that you can use for-- for example, the 4K looks at four isoenzymes of prostate cancer, four subtypes of BPH. When we look at those isoenzymes, you'll get a score, and if it's elevated, those patients have a higher risk of prostate cancer. The hot area right now is using exosomes, which are these tiny little extracellular vesicles that are released in prostate cancer patients.

What we can do is collect these exosomes in individuals and then analyze them, and if you have a preponderance or a surplus of these small little RNA, DNA, protein particles, you may have a higher risk of prostate cancer. Now, the urine biomarker area's really expanded. There's a number of commercially available tests. They typically are used in patients that have PSAs between 2 and 10. The FDA guidelines have put in place men typically over 50 or older that have PSAs between 2 and 10. In your individual that's 60 years old, comes in with tha, elevated PSA, after I do my exam, and obviously if I feel an abnormality of the prostate, I may go right to an MRI.

Given that in most of these patients, the prostate feels completely normal, I like using a urine biomarker. I've used blood biomarkers, I've used urine biomarkers. I like using the ExosomeDx test personally. I think it's a simple test to do. There is a test called SelectMDx, which is a similar test that these tests are different in some respects that the Select test uses clinical information. You might say, jeez, is there a family history of prostate cancer? Have you had a prior biopsy? So on and so forth. The Exosome test actually does not. There's a difference in how the markers, you know, are utilized, number one.

Number two, to obtain a SelectMDx test, you have to do a digital rectal examination. The reason for that is you're trying to release from the prostate, this marker that's tested in that SelectMDx test. What's different about the Exosome test is you don't have to do a digital rectal examination. I think that's a little nicer for the patient. When COVID hit and we weren't seeing these patients in the office, the company pivoted to doing this home collection kit. I could do a tele visit, just like we're sitting here talking today through a video. If I say, jeez, [Dr. Jose Silva]:, you have an elevated PSA of 5, you're over 50 years old.

You weren't coming into the office for a digital rectal exam, but I could send the whole kit to you and we could then do this Exosome test by just peeing in a special apparatus, sending the specimen off to Boston to be analyzed. Then that would essentially be a risk evaluation tool that I could say, your Exosome test came back at 25, which is above the cutoff of 15.6. The negative predictive value and the sensitivity are quite high, above 15.6, and you're a young guy, I want to do a biopsy on you. Whereas if it came back below 15.6, I would say the likelihood of you having prostate cancer is extremely low, and I don't think we need to do a biopsy.

What's nice is the Exosome test has been validated. There's been two large clinical trials. One was in JAMA Oncology in 2016. The other one was in European Urology. Over 1,000 patients were used in the validation study. Essentially what these studies showed is if I do this, I can reduce the number of biopsies I do in individuals by 27%. Think about that. If you have an elevated PSA and we do this test, 30% or a third of 100 patients may not need to get a biopsy done, and I'll be confident that they don't have prostate cancer, high-grade prostate cancer.

When we think about prostate cancer, in the past we've thought about prostate cancer as a single entity. In other words, if you had prostate cancer, it was bad and we needed to treat you. We now look at it a little bit differently. We know that people can have low-grade prostate cancer, live a perfectly normal life, and not have to get treated at all. It's really interesting. I was a professor at Duke for 11 years, and I essentially built my career on doing robotic prostatectomies. I've done over 2,200 robotic prostatectomies in my career. When I was at Duke, my active surveillance rates or patients that would come in with low-grade disease, was about 17%.

The likelihood, if you had prostate cancer and came and saw me back in 2005, I would say you got a Gleason 6 tumor, we need to take your prostate out, and you would be operated on by me. That would be a good thing because you'd do pretty well, but it may not be the right thing. Now, I look at my active surveillance rates and they're 45%. The likelihood, if you came in with a Gleason 6, average tumor, not a lot of disease, I'm going to tell you what we're going to do is more likely than not just follow you. You may exist and go on for your whole lifetime without any kind of treatment.

I tell patients, if you go on an active surveillance protocol, a third of patients eventually in their prostate cancer journey are going to get treated with either surgery or radiation, or focal therapy. There's so many different options today. Two-thirds of patients, 66 out of 100 are going to be able to go their whole life without any kind of treatment for their prostate cancer.

[Dr. Jose Silva]:
If you're following that one-third, where you come by a couple of years without any treatment or without risk of metastatic disease, I guess it's a win for the patient because you don't have to live with these possible side effects of either radiation or surgery.

[Dr. David Albala]:
No question. There are side effects with those. Getting back to the biopsies, here's a test that reduces almost a third of patients from getting an unnecessary biopsy. I've done a lot of biopsies in my career. I've been practicing for 30, almost 34 years now. I remember when I first started doing prostate biopsies, I started my career out at Loyola University in Chicago. We'd stick an ultrasound probe in. We wouldn't use any anesthetic, and we'd do these biopsies. It was cruel punishment to these men. They would be jumping off the table.

Over the years, we've been a little kinder. We now use lidocaine to do a prostate block, but it's still uncomfortable. There's no question. If you can avoid that number of biopsies, and here we have a test that does that, and it's a simple test. When I look at new tests, there are five things to me that make a difference between how to understand, should I use this test or not? I look at the efficacy of the test. Does the test perform in a way I want it to perform? In other words, if I do an Exosome test, is it efficacious to the patient? One could argue, yes.

It reduces the number of unnecessary biopsies. What are the side effects? There's not a lot of side effects from collecting a urine test. There are side effects if you do a prostate biopsy. Infection, bleeding are the biggest things, and patients have died in the past from prostate biopsies. That risk is really low. That risk still exists. What's the ease of doing the procedure or biopsy, or whatever test you're doing? A urine-based test where a patient can do it in his home, pretty nice to do. It's simple. He just pees in a little cup, and you're done.

Interpreting ExosomeDx Scores in Clinical Practice

[Dr. Jose Silva]:
Regarding the results of the ExosomeDx, the closer you are to 100, the more chances you have a high-grade cancer? Is that how it's read?

[Dr. David Albala]:
The higher the score, the more likely of a high-grade prostate cancer is going to be detected. If you have an exosome test that's 10, and you have an exosome patient that comes in and it's 50, he has about a 50% chance of high-grade prostate cancer. It's almost a one-to-one ratio up to 50%, and then you start to see it plateau off. If you come in and your exosome's about 30, they have about a 30% chance of a high-grade prostate cancer. We define high-grade prostate cancer as a Gleason 7 or higher. Gleason 6 is really not considered, you know, a high-grade prostate cancer. We use the term low-risk prostate cancer or low-grade prostate cancer.

[Dr. Jose Silva]:
We're talking about group 2 or above or intermediate risk or above?

[Dr. David Albala]:
Exactly.

Clinical Decision-Making with Elevated Biomarkers

[Dr. Jose Silva]:
Dave, in terms of, you mentioned the multi-parametric MRI, how do you integrate that to your practice? Are you using MRI fusion biopsies or what are you doing?

[Dr. David Albala]:
We are. Again, this has been a significant evolution and change in the way we think of things.

For a number of years, the best way to biopsy was doing a transrectal ultrasound. I remember when I was a resident, we would take patients to the operating room and do perineal biopsies, put our finger in, do it maybe either transrectal or transperineal and essentially biopsy, just putting-- we tried not to stick our fingers and have finger tissue in the biopsy specimen. Then ultrasound came along and that changed the dynamics. We could image, we could stick a needle in, but an ultrasound provided a random biopsy. In other words, you wouldn't know exactly where you were doing the biopsy. You know it's maybe right apex or right base, or whatever. Then MRI fusion biopsies came in, and that again changed the playing field. In those biopsies, you could do the MRI and it became a targeted biopsy. You could aim, when you fuse the images on the MRI with the ultrasound, you could target a specific abnormality that you saw on the MRI with the ultrasound, so you were sure to get that tissue. That's the difference. Even up to a couple of years ago, we were still doing regular transrectal ultrasound biopsies.

Because many insurance companies would only approve it if you had a transrectal ultrasound and it was negative, and the PSA kept rising. They've changed their guidelines now. I go exclusively to MRI fusion biopsies. I'm a believer in the technology. There is a cost with the MRIs and it's much higher than with an ultrasound, but I think the biopsies are better quality. Plus you also have a record of where the biopsies were taken. In other words, if you come in and I do a biopsy, and then your PSA fluctuates a little bit and then goes up again, I can pull your MRI up. I can see exactly where we biopsied and if you have a new lesion, it shows me where the biopsies were the first time. It's very useful information.

[Dr. Jose Silva]:
Dave, in your practice, are you using both? You're doing the MRI and the ExosomeDx?

[Dr. David Albala]:
I do. My workflow algorithm is PSA test, repeat it if necessary. Then men age 50 and higher that have a PSA between 2 and 10, those individuals, I'll get an exosome test. If the test is less than 15.6, I'll say I'll see you back in six months and repeat the PSA. If it's above 15.6, I'll set those patients up for an MRI fusion biopsy. We get the MRI and then we can target any abnormalities that are seen on the MRI. That's my workflow. You could do it the other way. You could do MRIs and then do the exosome test. There's different variations. We just recently wrote a paper showing how layering biomarkers with MRIs really does provide enhanced information to the clinician to diagnose prostate cancer.

[Dr. Jose Silva]:
I've been doing it the other way around. Back in COVID, I started doing the MRI, and since I've been doing MRI, I guide it. I get a lot of patients that are reading from the radiologist that says chronic prostatitis, but their PSA continues to creep up. Last couple of months, I started using ExosomeDx in the practice. Most of those patients, I will say the index is more than 15.6. Those patients that, let's say the MRI is negative but the ExosomeDx is positive or more than 15.6, are you doing a random biopsy? Are you doing a saturation biopsy? What are you doing with those?

[Dr. David Albala]:
Again, a rule of thumb based on clinical information is up to 50%. If your exosome test is 35, there's about a 35% chance of a high-grade prostate cancer. That's where you have to use a little bit of clinical judgment. If it's 17 and the patient is 78, you may say, listen, I'm not going to really worry about this. You're going to act differently with an exosome score of 20 in a 55-year-old versus 75-year-old. You use a little bit of clinical judgment. I like that one-to-one relationship really holds true for me. I can tell you if the exosome test is below 15.6, the likelihood of a bad prostate cancer, a high-grade, grade group 2 or higher prostate cancer, extremely low.

The beauty of the exosome is the negative predictive value, ie those patients that have numbers below 15.6, really probably have a very, very low risk of prostate cancer, and the sensitivity, it's much better. This is much better than PSA testing. It's much better than using the calculators, the prostate cancer prevention calculator, the European calculator for detecting prostate cancer. I like this test because it's simple and I can do it and patients do it at home. Then I can set up a video visit. Then if it's elevated, then I will do the biopsy in those patients.

[Dr. Jose Silva]:
If it's elevated, you will do the MRI first to see if there's a targeted lesion that you can biopsy, but you already are going to do the biopsy regardless.

[Dr. David Albala]:
If the number is just slightly elevated, I may not do the biopsy again, depending on the age and using that clinical information. Remember MRIs, there's a lot of variability with MRIs. It depends on reader subjectivity. The negative predictive value, if you have a very small lesion, if it's less than a centimeter lesion on the MRI, that's going to be a much harder cancer to detect. The location, the multilaterality and focality of these tumors. There's a lot of issues that go in with MRIs. There are many people that hang their hats on MRIs, but again, it's not 100% technology or we'd all be doing MRIs. We use them a lot. They're a useful test, but they're not 100% foolproof.

[Dr. Jose Silva]:
Probably more expensive, the MRI, rather than the urine test.

[Dr. David Albala]:
The urine test I believe is actually a little bit higher. Again, I don't know the cost of the urine test. What's interesting is these now, the biomarker, you know, ExosomeDx is in the NCCN guidelines. It's paid by Medicare. Many insurance companies, private insurers pay for this test. Like any new test, I talked about this earlier, looking at efficacy, side effects, ease of use, cost, and then durability, those are the five things. When I see a new technology. If it's, say, BPH, I ran the FDA trial for the low-energy microwave.

It was great on efficacy. We got good results. The side effects, it was pretty minimal, easy to do. The cost was reasonable. Where it failed, it was durability. After a number of years, three to five years, these patients all became symptomatic again. When I see a new technology, whether it's a urine test, a blood test, a new procedure, in my head, I think of these five categories and I say, does it check the box? To me, the exosome test checks those boxes. I've used it and integrated it into my workflow.

[Dr. Jose Silva]:
You convinced me. I already use it, but I'm going to change the way I use it. Like I mentioned, I use it after the MRI because I was already doing the MRI, but definitely probably it's easier, patients do it at home. I'll probably start doing it the other way around. Also I can start doing less MRIs and I can rule out patients already if they have a low index score.

[Dr. David Albala]:
It's a great adjuvant marker to use with the tools that we have to try to diagnose prostate cancer. Again, there are other tests. There's blood tests out there. There's other urine tests. You're old enough to know PCA3 where we'd go in and massage these men with their prostate. What I like about this test is we don't have to do that. The validation study really have shown that it can reduce not only patients that are undergoing an initial biopsy.

Jim McKiernan from Columbia wrote a very nice paper showing in patients that have had a negative biopsy, first biopsy, that you can use this to try to enhance and identify more patients that potentially might have had prostate cancer that was missed. These are really the risks at two populations that the test is approved for; patients undergoing initial biopsies, and patients that have had a negative first biopsy that you want to decide, should I do a repeat biopsy on?

[Dr. Jose Silva]:
Dave, you mentioned that there's data out there between comparing the MRI with or using it in conjunction, the MRI with the ExosomeDx. Can you talk about that a little bit more?

[Dr. David Albala]:
We just published-- we've just submitted a paper. It's not published, we haven't received any word on the paper, but looking at layering biomarkers. The first biomarker, PSA is a biomarker. It's a blood test. If that blood test is elevated, if then we add the exosome test to that and that's elevated, then we can enhance the detection of prostate cancer by doing an MRI. When you combine all those three pieces of clinical information, it's going to be a much higher value in detecting prostate cancer than just using a single test alone, whether it's MRI or PSA.

We know PSA is not prostate cancer-specific test. It's a good screening test. It's been used for years. I think it should continue to be used, but it's not sensitive enough to pick up the prostate cancers that we really want to identify. That's why I think this layering concept, much like what we've seen with advanced prostate cancer. When I train, if you have

metastatic prostate cancer, you either did an orchiectomy, the removal of the testicles, or you gave people injections to fool the body to shut down the production of testosterone. In 2023, patients with metastatic prostate cancer don't get just hormone injections or orchiectomy. We now are layering drugs like enzalutamide or abiretarone, or a variety of these newer androgen receptor agents to help with prostate cancer. When you look at the data, there's no question that this layering or this combination of different treatments is much more effective. I think it's now spilling into diagnostic testing, that we're using this layering to try to enhance our ability to pick up prostate cancer.

[Dr. Jose Silva]:
Just out of curiosity, a patient that has elevated the score, if you do a biopsy, have you had patients that have negative biopsies?

[Dr. David Albala]:
Sure. I've had patients that have-- again, this is not 100% foolproof, but the higher the exosome score, the higher the likelihood of detecting prostate cancer. If you have an exosome score that's 20 and you compare it to a patient that has an exosome score of 55, there's a difference. About 55% of those guys in that upper group are going to have prostate cancer versus 20% of patients in that other group. 80 patients, if I have 100 patients, we'll have no prostate cancer whatsoever. What we're trying to identify much like what the genomic markers do, try to identify the wolf in sheep's clothing, is that patient a candidate for active surveillance?

This test helps us identify those patients at a higher risk. All of these tools are risk assessment tools. We've now branched out from, do you have prostate cancer or not, to try to assess the risk? If you have low-grade prostate cancer and low risk, more likely than not you don't need to do anything. That's where this evolution, and over my 34 years of practicing, I've really seen this change.

Like everything else, things change. When I first finished my residency and did my fellowship in St. Louis, we were still doing ureterolithotomy, making an incision in the ureter to take a stone out. We wouldn't think of that today in 2023. We have scopes that are small lasers, shock waves. That's the beauty of what we do. There's this evolution of technology. These biomarkers and MRIs are, are just evolutions of different technologies to make us better at detecting different diseases.

The Future of Urology: Personalized Approaches to Prostate Cancer Screening & Care

[Dr. Jose Silva]:
Exactly. Dave, I think you already summed it up, but anything else you want to add?

[Dr. David Albala]:
To me, the takeaway message is be smart, get screened. If you're at a high-risk group or you have a family history, get screened at age 40 to 45. If you don't, if you're not a high-risk group, you can get screened at age 55, but the bottom line is get screened. What you don't know is ignorance is not bliss. If you have prostate cancer and you're diagnosed with it, you don't necessarily need to get treated. Almost 50% of patients that are diagnosed today don't need to get treated. We can follow them. That's very unique to prostate cancer.

I can't think of a single disease state in which you follow these. Early on, many patients were essentially bewildered that you would come in and I'd say, Dr. Silva, we know we've diagnosed prostate cancer, but we're not going to do anything. People didn't understand that concept. They now understand it. The takeaway message is have a discussion with your physician, shared decision-making. Each case is individualized. We're getting more towards personalized medicine. All of these tests in some ways are ways of personalizing your medical care.

One shoe doesn't fit everybody anymore. I think get screened. If you need to get a biopsy, there are tests, the exosome is a perfect example, that you may prevent 30% of patients from getting a biopsy that's not necessary. It's been a great profession. I've had an amazing career. I've seen so many great changes. I wish I could do it all over again, but I'm getting old and the younger guys are coming through. They're fast out with the robot.

I think that my early days when I did a robotic prostatectomy at Duke, my first one took me eight and a half hours. Think of it, eight and a half hours to take a prostate out. I could do an open prostatectomy in an hour and a half. Today I can do a robotic prostatectomy in an hour 30 minutes or so, and the results are really terrific. It's great to be a physician. It's great to be a urologist. The beauty of what we do is we really see how we impact our patients. There are tests out there that really help us do our job much, much better.

[music]

[Dr. Jose Silva]:
Excellent. Well said. Thank you, Dr. Dr. David Albala Albala, to being in BackTable.

[Dr. David Albala]:
Thanks so much. Have a great day.

[Dr. Jose Silva]:
Thanks.

Podcast Contributors

Dr. David Albala

Dr. David Albala is the chief of urology at Crouse Hospital in Syracuse, New York.

Dr. Jose Silva

Dr. Jose Silva is a board certified urologist practicing in Central Florida.

Cite This Podcast

BackTable, LLC (Producer). (2023, August 16). Ep. 112 – Preliminary Complementary Data for Pairing mpMRI and the ExoDx Prostate Test [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.