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🎙From PSA to Personalized Prostate Care, Part 2 Ep. 292

• Dr. Michael Koren, Dr. Ali Kasraeian • Episode 292

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Urologist and president of the Duval County Medical Society Dr. Ali Kasraeian joins Dr. Michael Koren to update us on recent advances in Urology. In Part 2 of this series, Dr. Koren and Dr. Kasraeian explore into the controversial history of PSA testing. Dr. Kasraeian explains how this simple blood test revolutionized prostate cancer detection while creating challenges around overdiagnosis and overtreatment. The doctors also talk about how modern approaches to prostate screening have evolved to balance finding dangerous cancers while avoiding unnecessary interventions.

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Announcer:

Welcome to MedEvidence!, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts Hosted by cardiologist and top medical researcher, Dr. Michael Koren.

Dr. Michael Koren:

Hello, I'm Dr. Michael Koren, the executive editor of MedEvidence! I've been having this fabulous discussion with Dr. Ali Kasraeian and we talked about your background and some of the wonderful things that you've been doing for our community. And now let's jump into a controversy and you and I have had this discussion before, but I think it'd be super interesting for our listeners and viewers to hear it and the discussion is around the use of PSAs, or prostate-specific antigens, to diagnose prostate cancer.

Dr. Michael Koren:

And when I was a resident and early in practice and was practicing some internal medicine, I would routinely get PSAs on my patients, typically men anywhere between mid-30s and 55. And we would be looking to see if there are early signs of prostate cancer. And then the rules changed a little bit or the policy did, and that was no longer looked at as something that we should be doing on a regular basis. So why don't you educate our audience a little bit about the history of that and the controversies around that and kind of where you stand?

Dr. Ali Kasraeian:

So the PSA is a very inexpensive, very simple to get lab test that we use as a screening test to see what the risk of having prostate cancer may be. And the controversies that lie around this is the potential of over-diagnosing prostate cancers that may not kill someone, low-risk, low-volume prostate cancers that people could live with, versus over-treatment of those same cancers. So that has been, you know the, the albatross that has has really plagued prostate cancer screening for a long time, and since its inception it's been this, this discussion of what to do. When you know, in the late eighties, early nineties, PSA developed. It was a really wonderful tool that we had nothing.

Dr. Ali Kasraeian:

People would show up with metastatic prostate cancer and you would be lucky to find organ-confined prostate cancer, to be able to do a prostatectomy, which Patrick Walsh at Hopkins did some wonderful studies to find the anatomy, to do nerve preservation and better prostatectomy.

Dr. Ali Kasraeian:

So then everyone that was then diagnosed with prostate cancer. We had a sharp increase in the diagnosis of prostate cancer and a really, really profound decrease in the mortality from prostate cancer, which then continued for years and decades to come. The challenge with that is, the treatments for prostate cancer were associated with significant quality of life implications, such as incontinence or erectile function issues that were really profound. And so the discussion was if you have a potential prostate cancer that is low risk and people could live with and it was not fatal, is it worth the diagnosis and the anxiety related to it and the potential overtreatment with treatment alternatives that may have impact? And prostate cancer-specific antigen, or PSA, is not prostate CANCER-specific antigen, it's one that could be elevated for other things and enlarge prostate inflammation and those type of things. So we're kind of plagued with the appropriate way of screening. So more appropriate, smarter screening and you know the counseling and kind of how over the years have we used better tools to be more personalized and precise with our screening discussions?

Dr. Michael Koren:

So, just for the audience's knowledge and for my knowledge, what are the current recommendations about PSAs? Never get them. Get them in certain patients. Just break that down for us.

Dr. Ali Kasraeian:

So right now with the AUA, the recommendation is around 45, begin screening for prostate cancer, and that's been kind of like a that constantly changes. Different organizations recommend different things and if you are at a higher risk population.

Dr. Michael Koren:

When you say screening, is that a rectal exam or is that a live test now?

Dr. Ali Kasraeian:

So you know the PSA is what you talk about. The rectal exam remains controversial, but most of us that do a lot of prostate cancer tend to recommend getting a rectal exam and a PSA test as a screening measure.

Dr. Michael Koren:

So that's still in the books as something we shall do at age 45.

Dr. Ali Kasraeian:

At 45.

Dr. Ali Kasraeian:

You know the rectal exam by itself there are studies that show it may not be as impactful. I personally do a rectal exam because it gives you a lot of information. The size of the prostate is a guesstimation. It's not as precise as getting an ultrasound or an MRI scan per se, but it gives you an idea of if someone has a huge prostate, a medium-sized prostate or a large prostate and you look to make sure there are no nodules. You know if someone does have a nodule on their prostate you could still have a low PSA and have a nodular prostate. You can make sure there are no rectal nodules or rectal masses and things of that nature. So I think there's impact and positivity in doing a rectal exam. So I still do rectal exams.

Dr. Ali Kasraeian:

Risk and high-risk populations include a family history of a prostate cancer, especially a brother, father, first-degree relative and people of African ancestry and African-American populations are a higher risk of prostate cancer and with the African-American population they had an almost twofold increase in more aggressive and fatal prostate cancer diagnosis at an earlier age. So earlier screening kind of starting at 40, is an easy way to kind of think about that. So I try to make things simple for people, if you have no family history, no increased risks 45, and then everyone else at 40. And you can kind of at 45,. You can think about that as the same timeframe to begin getting that first colonoscopy.

Dr. Michael Koren:

Okay, and when do you stop screening for PSA? This is where the whole concept that later in life maybe it's not going to be particularly helpful and just chase you down a rabbit hole. So one.

Dr. Ali Kasraeian:

You know 70 comes up as this age. That comes up in a lot of the guidelines. However, you kind of think about that in terms of, you know, age as chronology but also level of health. You know there's 70-olds that are running triathlons and then there's 70-year-olds that have 900 heart stents and are walking around with an oxygen tank. So you assess that 10- 15-year lifespan and possibility of being alive at 10- 15-year, which is not the easiest thing to do, but there are a lot of ways you can potentially assess that and you look at that.

Dr. Ali Kasraeian:

And really one thing that's really important to think about these conversations a lot of times are had at urology meetings and within urology venues, but it's important for this to be had at the primary care doctor's office because a lot of times we have these conversations when the patient already has had a PSA and they're like 85 years old and they show up with an elevated PSA. So then you got to figure out do we want to make sure that we don't have metastatic disease now, because I'm not excited about getting, you know, prostate biopsies on an 85-year-old for their PSA being elevated, but you want to make sure what the reason you're doing that is from that standpoint. So those are the discussions to have at the primary care level and that's where we are working very hard as urologists to figure out the best way to come up with the best screening aspect at the beginning of the conversation which is there?

Dr. Michael Koren:

So just for clarity. So somebody who is considered low risk doesn't have any of the high risk markers. Do you still recommend primary care physicians check at 45 and yearly, or every five years? Or give us a Good question, yeah.

Dr. Ali Kasraeian:

So when you talk the guidelines, talk about a patient-centered discussion, and a lot of times when you talk to your patient, they have buy-in on checking it on a yearly basis and it's an inexpensive test to do If their PSA is very low, and most of the world's population's PSAs are actually less than one then you can actually come

Dr. Michael Koren:

And is four still considered above normal?

Dr. Ali Kasraeian:

So in a lab test, but we're actually looking at that a bit more. Four would actually come up with as a two standard deviation increase from two, two and a half we're actually looking at could two and a half be the new normal per se? A study was actually just published that people in their 70s the world's majority of PSAs are actually less than one at 70.

Dr. Ali Kasraeian:

And if your PSA at 70 is less than one, your risk of having a clinically significant prostate cancer is very low. There was a great study done out of Malmo, sweden, years ago, where they went it was a natural history of disease study and they went back and looked at blood and looked at PSAs. That first PSA at 45 to 49 for average risk patients was the most telling of your risk of prostate cancer. If your PSA at that age was 1.5, that represented about 44% of people who had clinically significant prostate cancer in their lifetime. If at 60, you had a PSA less than one average risk, your risk of clinically significant prostate cancer was very, very low. And that study showed at 70, kind of similar type of thing.

Dr. Ali Kasraeian:

So you can come up with an algorithm of how frequently to check PSAs based on what those PSAs are at A. So if your PSA is less than one at 45, could you check less frequently. If it's two, it is different from that standpoint and that's what we want to kind of look at. The other thing is knowing your family history, knowing if there's any kind of bracket gene positivities, even in the women in your life. So that becomes important in terms of how often you check your PSA. For you personally, the easy answer is if you're getting labs anyway and you check a PSA every year, it's not an expensive test. But as a population discussion you can make decisions based on what your individual PSA is in a conversation with your primary care doctor, so if it's less, than one, risks are much lower.

Dr. Michael Koren:

And, as you alluded to before, the concern is that there are a lot of false positives and I imagine that if you have prostatitis from infection or something else, your PSA goes up.

Dr. Ali Kasraeian:

Absolutely, and I want a couple of things. We recommend to people Avoid ejaculation for two to three days. If you have any kind of symptoms you're worried about, talk to your urologist. You know a lot of the things. When people look up, you know prostate cancer a lot of urinary symptoms come up which are usually associated with BPH benign prostatic hyperplasia which is a benign entity. It's not a cancer-based entity from that standpoint. So that's something for people to be mindful.

Dr. Ali Kasraeian:

Often, most of the prostate cancers that we diagnose are really simply from a lab test that was obtained, often with patients not knowing that they had the lab test done, being elevated. So that's why the importance of screening is so profound. And you know, looking at the data, you know in 2008, there was an initial screening recommendation against prostate cancer screening by the US Preventative Services Task Force. That then was strengthened in 2012 with a grade D recommendation and that really led to a significant decrease in screening, especially at the primary care level, which we now see the downstream effect. And you know, multiple years later, that grade D recommendation, after re-evaluation of the

Dr. Michael Koren:

Grade D meaning they did not recommend it at all.

Dr. Ali Kasraeian:

Now it became a great C recommendation, meaning that you can have a patient-centered discussion with your doctors about the risk benefits and that has increased screening. But we downstream have seen a significant stage migration more metastatic disease, more high-risk disease.

Dr. Michael Koren:

Because we're not diagnosing these earlier.

Dr. Ali Kasraeian:

We're not diagnosing earlier and in populations like the African-American population. That's a big deal from that standpoint and those are really, really profound. So if you have people men in their 50s not being diagnosed with high risk disease, the implication of that is profound.

Dr. Michael Koren:

So we always like to talk about the fact that things should be personalized when you're getting medical information from the internet or from Med Evidence!, and so let's come up with a couple of scenarios so people can understand things in a more personal way. 48-year-old guy not 100% sure of his family history but thinks maybe somebody had prostate cancer two generations ago. He comes in PSA, comes back 2.8. Do you freak out? What do you do as a next step?

Dr. Ali Kasraeian:

No, I mean. So why always repeat a PSA after one, you know, unless you have a trend? So you kind of go back and look if they've ever had any kind of PSAs and things of that nature. Then we kind of talk about repeating it. There are studies that show that even kind of, you know, giving antibiotics doesn't make a difference unless they have symptoms. You know prostatitis. That's where the rectal exam helps. If you have a warm, tender prostate associated with prostatitis, then you can treat that.

Dr. Ali Kasraeian:

But repeating, you know, is this a fluke? Is it elevated For someone in their 40s? You know age-specific PSA. Your PSA should be less than two and a half, you know, from that standpoint. So then you kind of look at if the PSA is elevated. I was, you know, I'm a big, big believer in multi-parametric MRI scan. This is a very specific MRI scan that looks within the prostate to see are there any areas of concern. Because now we have the technologies that if there is, you can actually merge the MRI and the ultrasound and target that area. And if that area is the only place that's concerning, then we could potentially just treat that.

Dr. Michael Koren:

So you repeat the 2.8 before you do imaging, I imagine.

Dr. Ali Kasraeian:

Absolutely Okay.

Dr. Michael Koren:

And then your go-to is ultrasound, or is it MRI or this?

Dr. Ali Kasraeian:

Yeah, so ultrasound is not the most diagnostic tool for "aha. There's the prostate cancer. There's a very, very high frequency ultrasound that can be used at a time of biopsy that can give us more information to see "aha. There's a better place to do, but in terms of a diagnostic tool that helps guide and shape biopsy decisions and also as a tool to do a better biopsy the multi-parametric MRI scan. And if someone can't get the contrast, the gadolinium, we could do what's called a bi-parametric MRI scan. But that can give you a target, if one exists, to do a targeted biopsy. But also if the MRI is negative, that's great information from that standpoint to not only help guide a better, more accurate, more precise diagnosis, but also it could help shape our discussions of what to do next.

Dr. Michael Koren:

So the 48-year-old guy 2.8, gets it again 2.8,. You're going to do imaging.

Dr. Ali Kasraeian:

I'm going to do imaging and that helps shape our diagnosis. At 48 with a PSA of 2.8, if the MRI scan is negative, you know we have to be mindful that you could still have about a you know, 20 to in two amazing studies, the PRECISION trial and the PROMISE trial, which helped land the impact of MRI scan for not only finding more clinically significant disease, which means intermediate and high-risk prostate cancer, meaning prostate cancer that if you found you would treat Low-risk prostate cancer, which there's a thing called the Gleason score. It's how you grade the prostate cancer. Lower-risk prostate cancer is the Gleason score of six PSA less than 10, a small nodule or no nodule those you can monitor with an active surveillance. We hope not to find those. If we can, we want to find the ones that we would treat and could impact your life potentially in the future If you find a small targetable lesion like that. Now we have technology that you could potentially just treat that Interesting.

Dr. Michael Koren:

So take that same 2.8, but now it's a 70-year-old person. You just sit on it, or do you still do the same thing? Look at their trend.

Dr. Ali Kasraeian:

If they've been 2.8 for two decades, especially if they've had previous biopsies or things of that nature, you can see If it's a change, if they've had an increase in their PSA velocity. They've been one their whole life and now it's 2.8, you repeat it. If it's still 2.8, then you can talk to them. You know, I would do an MRI scan. It gives you the size of the prostate. It can give you some idea if there's a targetable lesion. Because that same pathway Could you do a better biopsy and you can also use biomarkers.

Dr. Michael Koren:

Right, and the reason I'm creating those two scenarios is that there is a notion, as I understand it, that being diagnosed with prostate cancer later in life tends to have a more benign course than somebody that's diagnosed earlier in life.

Dr. Ali Kasraeian:

Yeah, and a couple different perspectives. One the average age for being diagnosed with prostate cancer is 66, 67 years old and the implications of how to manage them depend on a few things. One, the stage and grade of the prostate cancer. Like I mentioned, there's Gleason score. Pathologist looks at the cells on the microscope and assigns two numbers. The first number is the most common, second is the second most common. Adds them together to a total score. As the numbers increase, how different from normal those cell types are increases and the possibility of it in the future at some point getting out of the prostate increases. So a Gleason score of seven is kind of a fence that divides aggressive cancers, like eight, nines and tens, from less aggressive cancers, like six we don't really see fours and fives anymore Within the seven family and 10s from less aggressive cancers, like 6. We don't really see 4s and 5s anymore Within the 7 family. A 3 plus 4 is less aggressive than a 4 plus 3.

Dr. Michael Koren:

So you're less worried about over-treating people with prostate cancer because you feel like there's ways of characterizing the cancer so that you're really treating the people who are at higher risk over time.

Dr. Ali Kasraeian:

Yeah. So I'm a big believer in active surveillance have been for my whole career. So if you have a low volume, low risk or even you know a low risk prostate cancer in general, you can do what are called genomics tests. You can assess the biology of that disease to give you a picture of, you know, the cat in the bag analogy.

Dr. Ali Kasraeian:

If you have a cat in the bag. Is that cat going to grow up to be a small kitten? Is it going to be a cat that's a timid cat, or is it going to grow up to be a ferocious tiger? You can make decisions, and it can actually. We have testnodes that can give you predictive information. What's the likelihood of passing away from this cancer, based on your biology and clinical information, in the next 10 years? If we treated it, what's the risk of metastasis in that time? And then, based on that information, we can counsel. You're a great candidate for active surveillance. Every guideline talks about active surveillance for low-risk disease. If we have intermediate disease, what's the volume? Is it localized? We can do artificial intelligence technology.

Dr. Michael Koren:

Well, let's get to that. I'm going to take a quick break here, but this is fascinating. So we talked about the controversy about PSAs and gave a little bit of information about how you would customize that for different patient populations. But let's talk about the future in our next segment.

Dr. Ali Kasraeian:

Absolutely

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