Prostate Cancer Awareness Month (Part 2): Diagnosing Without the Panic

0:00This is an iHeart Podcast. Guaranteed Human.

0:31positive metastatic castration-resistant prostate cancer, or PSMA-positive MCRPC, who have already been treated with hormone therapy and are considered appropriate to delay chemotherapy. Blue Victo involves contact with radioactivity, which may increase the risk for cancer and cause fetal harm. Drink plenty of fluids, urinate often, use contraception, and talk to your doctor about ways to reduce the risk of exposing others to radiation during and after treatment. Blue Victo can cause low levels of blood cell counts, kidney problems, and infertility. Tell your doctor if you have weakness, pale skin, shortness of breath, bleeding or bruising more easily, and infection or changes in urination.

1:05Side effects include decreased blood cell counts, tiredness, dry mouth, nausea, appetite loss, joint or back pain, and constipation. Ask your doctor about Fluvicto because every day without cancer progression is a victory. Visit Fluvicto.com to learn more.

1:31Let's talk about the mailroom Welcome to the mailroom Welcome, welcome, welcome back to the mailroom. Dr. Mills back here with Jordan Runtai again. We are part of this multi-part series with Dr. Wayne Brisbane. We're bringing him back today to talk about diagnosis. For those of you that listened to the last episode, we're walking through a patient journey, a 55-year-old male that is referred to Dr. Brisbane, a prostate cancer specialist here at UCLA, who has a bump in his PSA, went up from his baseline, and his primary doc said, hey, you know, you should probably get this worked up. So we learned all about screening on the last episode.

2:13A lot of great take-home points that should arm our audience to be able to be very informed when they go into their doc the next time to ask about prostate cancer screening, even beginning as early as age 45. Guidelines are a little bit squidgy on that. So the bottom line is if you feel you have a need, family history, maybe even just a curiosity of longevity, that you want to get screened relatively early. And screening has changed over the years from just one blood test to serum biomarkers, urinary biomarkers, and MRI. And so that's going to be the natural segue into the diagnosis segment of this trilogy.

2:53Dr. Brisbane, welcome. How are you, man? I'm doing so well. Thanks so much. I really appreciate you having me back. Was it leg day? Was it chest day? What was it today? You know, today was leg day, actually. I had leg day, too. I just came from leg day. I'm still recovering from my marathon I ran that I think leg day is going to be 2027 for me. How'd you do? I mean, I'm here. I'm awake. I did not end up on dialysis. So for me, it's all a win. I got a very heavy medal saying I finished the marathon. and a lot of high fives and bananas. So it was a really fun time. I ran it with my son who was already back in the hot bath in the hotel a good hour before I made it back.

3:36So we trained together, but we certainly didn't run together. You talk about aging well, Wayne, and you've watched me age for the last eight or nine years and we've known each other. And, yeah, I'm telling you, 30 years puts a lot of mileage on these legs and these hips and his back. I get it. But I'm happy I did it. It was a great feeling. It was just so fun to be out and seeing, first of all, the weather in Houston in January. Oh, it's just like one of the greatest towns out. I mean, big shout out to H-Town for their hospitality. It was amazing. But the weather is perfect. And there's just so many people out there supporting you.

4:14And you're part of this just really great feel-good moment where you're competing against yourself at my level because, you know, the guys that won the marathon could have run three in a time. It took me to run one pretty much. And then it was even great. Like there were the guys that had finished the marathon, they had their medal on. They came back onto the, you know, around around mile 26 and were high-fiving, being like, you got this, man. Oh, that's so cool. Dude, that is like, you could have been all drinking beer. But you're done and you came back. Oh, so great. So, no, I loved it. It was an amazing experience.

4:45And I'm actually not that sore. So I do need to get leg day in next year. But enough about this. Let's talk to our guys a little bit more about our patient that's in your office. You have a plan for him. His PSA is up. You're not going to say we got to go get a biopsy. You're going to tell him, what do we do now? Yeah, totally. So we talked a little bit about, you know, PSA. It's a thermometer. It is not a cancer test. It is a risk stratification tool, okay? It's like a thermometer. Just like if your temperature goes up, you might be running. If your temperature goes down, you might be sleeping, but you could also have a fever and you might be sick from a flu or something like that.

5:24But you'd be pretty, pretty skeptical if you got a fever, you went to your doctor and they said, hey, we're going to take you to the operating room for take care out your appendix. You'd say, well, don't you think there's a couple more tests we should do? And prostate cancer is the exact same thing. So PSA is your thermometer. If it goes up, there's several different things that could cause it to go up. Cancer is on that list, but it's actually not the top of the list. And we do need to take a look at this a little bit more extensively. Our main tool is MRI, prostate MRI. MRI is not perfect, but it has about a decade or more data now that shows that it's an extremely powerful, it's actually more like 15 years now, a really great test for separating those men who have cancer versus those who don't.

6:12Okay. Once you go and get in the MRI, people might want to know about that, what that feels like. So it's the, one of the questions I get is why does it have to be so tight? Like, why does it have to be so close to me? You know, I go and get a CT scan and it feels like I'm going through like a, like a little donut and it's open and it's great, but I go into this MRI and it has to be super, super close to me. And that has to do with the MRI and CT scanner acquire images very differently. A CT scanner is shooting an x-ray. You can think about it a regular x-ray, but then it's a CT because it's computed tomography.

6:48So they're using a computer to get all these little x-ray beams from all around in a circle and then realign them. So that is little x-rays that are going through your body. An MRI is based on magnetics. And so this is magnetic resonance imaging. So the reason why they take, you know, you can't have any metal in that room, they take away your phone, all that kind of stuff, because that magnet that is always on, okay, that that kind of cylinder that you lay in is a magnet. And they'll talk about the strength of that magnet in Teslas. And so it's very common to have a three Tesla magnet, occasionally, you'll get one that's 1.5.

7:25They have some that go up to 11 Tesla, usually only for research, but the in general, as those magnets get bigger and bigger, as far as their strength, they tend to get closer and closer to the cylinder gets smaller and smaller. And so this idea of an open MRI is a good concept for people who are claustrophobic, but it is usually a 1.5 Tesla magnet. It's a little bit open and that decreases the resolution because what the magnet does is it basically takes all the water molecules and it kind of aligns them in your body. And when you hear those big thuds, you're going to hear these big thuds in the MRI.

8:01That's these electromagnetic coils reorienting the water molecules at a perpendicular angle. So they're coming in and going against the water. I'm not an MRI physicist, so this is a little bit of a watered down version, but basically it's reorienting your water molecules and then they're measuring how long it takes for your water molecules to realign to that big magnet. And that produces an image. And so that's how you get these MRIs and different tissues in your body are going to react differently. So fat versus water versus muscle versus bone. Those all look different and those water molecules realign differently.

8:39And that's how you can get the separation of these different tissues. Well, normal prostate tissue looks very different than cancerous tissue. So cancer tends to be cellular growth that's unchecked. And so it grows very fast and it tends to grow very close together. So it creates more density. And that's usually what the MRI is picking up. And so we can use that looking for areas where the cellular structures are growing close together, and that can be identified on MRI. Now, that's kind of a, the MRI will then be interpreted by a radiologist, and so the radiologist will get all these pictures there, and they will give us a score, okay?

9:19And we have to come up with, this is a score that, as you mentioned, was very much involved here at UCLA. We had kind of the development and evolution of this score took several years, and a lot of UCLA physicians were highly involved in developing this score. It's basically a one to five score. One is perfection. It's beautiful. There's no abnormalities. Everything is perfect. I actually very rarely see that score because it's one of those things that if you're a 20-year-old getting an MRI of your prostate, that might be what your prostate looks like. But as we know, as we age, there's things that happen.

9:55Your joints probably don't look like they were when they were 20 either. So a lot of the times you would get a score of two. It means that there's no cancer. It's not perfect, but there's some little scar tissue, some degradation here and there, nothing to worry about, but it's a level two. And that means that we don't really see anything that's concerning for prostate cancer. Level three would say there's some cellular density, but it's not enough that it can be really measured. The radiologists can see it, but they say, you know, I just can't quite measure it. Okay, and that's, some radiologists might have some nuance with my description, but this is a general way to understand it.

10:31So it's what we call equivocal, okay? They can't quite measure it. Level four is they can measure cellular density. And there's some specific sequences in the MRI where you can measure cellular density. But it's less than 1.5 centimeters, and it doesn't look like it's pushing on the wall of the prostate at all. and five is they can measure cellular density but it is greater than 1.5 centimeters and it or and or it's pushing on the wall of the prostate and so that's kind of the levels and as you go from one to five the risk of prostate cancer goes up as you might expect in the coast so one and two has about depending on who you read maybe a 12 to 20 percent just risk of prostate cancer which I'll come back to a level three has about a 30-ish percent risk of prostate cancer level four about a 60 % risk of prostate cancer and a level five, about an 80 % risk of prostate cancer.

11:22And we'll get into kind of the grades of prostate cancer, but this would be those prostate cancers that you do want to know about, what we call clinically significant or prostate cancer that could spread, has the biologic potential for spread. Right. So then that gives you a little bit of shared decision-making with your patient, it sounds like, right? Absolutely. If a guy comes into you and says, whoa, whoa, you just said a two gives me still a teen to 20 % chance of prostate cancer. I can't live with that. Yeah. Can you, I mean, Dr. Brisbane, are you going to biopsy? Will you biopsy a one or two?

12:00If a guy just says, look, I can't sleep at night, or do you reassure, or how do you walk through that diagnosis? Great question. So what we oftentimes do is, and so that's a good point. So we said this MRI is looking for cellular density. And how would an MRI miss a cancer? Well, it would have to be something that was small, meaning that the cells hadn't packed together quite enough to really throw out a magnetic signal that the MRI could pick out. So that's probably the most common one is the cells are small. Or the cells might be hiding behind other things that are cellularly dense. Okay, so there's actually a couple zones in the prostate.

12:41The prostate's a weirdly shaped organ, but it kind of resembles if you ever wore a slipper where the toes are missing, you know, those flip-flops that you wear at the pool maybe. But if you slide your foot into that, that's kind of what a prostate looks like. The flip-flop portion is what we oftentimes refer to as the peripheral zone. It's on the periphery, and that generates about 80 % of prostate cancers. But your foot sitting in that slipper is probably, it's called the, that's the transition zone, if I can make the analogy. And that area is actually the part that causes more urinary trouble.

13:19The urethra is the tube that runs through that. That would be basically your foot. And your ankle is right around where the bladder sits. And then the penis would be kind of where your toes sit. And so it's kind of this area that's going through the peripheral zone. And that transition zone, about 20 % of prostate cancers do occur in the transition zone. but that area is much more cellularly dense. Okay. And so prostate cancers can hide in that area. Thankfully they're less common, but they can hide in that area. Okay. So that can be a way that an MRI can miss a prostate cancer. One would be small, one would be in the transition zone.

13:51And then there's some cancer, we call them phenotypes where the cancers just don't pack together quite as much. They kind of, they kind of spread out a little bit more and they have more like a, like a spider with, uh, with legs. They kind of have more tentacles and less of a big body. And so this is, these are the three ways that the MRI can miss a prostate cancer. And that's how you get to that 20%, even with a PI-RADS, that's the score too. I think you just, actually, I think you just invented our first swag merch is to have prostate shaped pool shoes. Yeah, yeah, right. Exactly. Can we get a 3D printer on that and see what a prostate pool shoe looks like?

14:28I think they would sell very nicely. Of course. I mean, and they'd be anatomically great. You could, you know, maybe we could do as part of your HSA spending. I love it. Open enrollments around the corner. I'm sorry. Yeah, go ahead. So actually, that was really, as much as I made light of it, very good analogy in terms of what the privacy looks like and how you can get a little bit lost in the MR. Totally. And so you can use that data in combination with your PSA, your age, the digital rectal exam we talked about, that's an optional thing. Any prior history, family history, stuff like that. You can add that into an online calculator.

15:07We have one that's available. Everyone can use it. It's PCRC. That's Prostate Cancer Risk Calculator, MRI. It's available online at UCLA. And that will compare you to 2 ,300 other men that we've biopsied, men that will tell you what your risk of clinically significant prostate cancer is. And so that changes the MRI from a biomarker, or sorry, from an imaging to a biomarker. It basically says, this is your picture. This is all the features. We compress them together. We compare you to a large cohort of men. We tell you what your risk is. And so I actually had a guy with a PyRADS 3 the other day that you would usually consider PyRADS 3, you should biopsy 30%.

15:45But when we put his calculated values in, his risk was only 6%. And so I said, hey, would you like to defer biopsy or would you like to go photobiopsy, he chose to defer. And so we'll continue monitoring his PSA for about a year to maybe two. We'll see what the trajectory is, and then we'll kind of see how that goes. I've had another guy with an MRI of two, or PIRADS of two, who has PSA density. His PSA was too high for his prostate size. We call that PSA density. And, you know, his age and all these features came in. He actually had a negative MRI, but his risk of prostate cancer was 56%, okay?

16:20And so you can have a negative MRI combined with multiple other variables in this calculator and you can go and kind of risk stratify as using multiple variables. And we hope that with time and more inputs and perhaps with some machine learning, we can get these accuracies to go even up. So that's some nuance. The other thing that you can use is you can use other tests on top of the PSA and urinary biomarkers are one that I particularly enjoy using just because they're easy to implement. I can send them to your house. And if you have a negative MRI and a negative urinary biomarker, some work out of our group and then also the group at UCSF has shown that your risk of prostate cancer drops precipitously if you have a double negative.

17:29how do you feel about guys that do really ultra preventative health screening right so if a guy has a PSA of 0.5 and he says no no no I got here's I got a bag of cash and I want to do an MRI plus or urinary biomarkers. Is that a thing? Do you have people ask about that? And because I know, I mean, things, you know, there's so many of these whole body MRIs that that are fascinating. It's a huge ethical debate, as well as a cost debate. And, but you know, people have money, and they don't want to get prostate cancer. Yeah. What is the diagnostic accuracy of somebody with an incredibly low PSA going through that next step?

18:07Yeah. So in general, I view this in two different ways. There's the population-based answer, and then there's the individual-based answer. So from a population standpoint, when I take my population science hat on and I say, how useful are these whole-body MRIs for a population compared to PSA? The answer is unequivocally not that useful. But for gentlemen who say, I accept possible false positives, meaning that I go through and the MRI picks up a little bit of inflammation in the prostate, or it picks up a little weirdness that I was born with. It's like a mole on the skin. It's fine. So those false positives will pick up quite a bit.

18:50If you have a PSA of 0.5, your risk of prostate cancer is quite low because the PSA has a very good negative predictive value. It's good at ruling prostate cancer out. And so I don't know if there's that much additional benefit. And in general, what I tend to do, those MRIs, the whole body MRIs, I get no money from them. But I do think that they're interesting. They have to go from the head to the toe. And they can't spend 18 hours in the scanner, right? You've got to do this in an hour or two. And so they have to be very choosy about which sequences on the MRI they pick. And each, as we said, you know, different tissues in the body have different responses to magnets.

19:31And so you can't image the head the same way you image the prostate, right? They're two very different sets of organs. And so you have to pick one thing that kind of does everything okay. And in general, that's a T2 weighted image that they just kind of run from the head down to the foot. And that will pick up bad things, really big things that are bad. But in general, the hope is for these prostate cancers to pick up small things when you still have a chance to intervene. And so at the level of the prostate, it's probably not your best test. But I still have guys who do it. I bless them. If they have something that's a false positive, we work it up.

20:08We just usually get a dedicated MRI of the prostate. Oftentimes the thing disappears or we'll get some PSA and we'll use our risk calculator. So I just kind of use it as another screening test. And you should know that they're running a huge, huge test, kind of clinical trial in England called TRANSFORM, where they're actually going to use MRI instead of PSA as a screening test. So this would not be necessarily diagnostic. It will be biparametric MRI, meaning that they're going to choose slightly different MRI sequences. so they can run it faster and cheaper. And they're going to just do that as a screening.

20:42So everybody gets one, just kind of like a colonoscopy. When you turn 40, you get one of these biparametric MRIs. We're going to see what the risk is. The other thing that they're running in this transform study, and then we're working on here at UCLA, and then also has been worked on in England a bit, is running a genomic test, right? We know family history is very important. So we can say, hey, you know, my brother had prostate cancer. My dad had prostate cancer. My grandfather had prostate cancer. And I've had some guys where they say, you know, I'm pretty much going to get prostate cancer.

21:07Or how do I be very careful? And so we'll just increase their screening frequency and stuff of that nature. But we can quantify genetic risk through a cheek swab. And basically, you can spit in the can, send it over to us, and we can use these various tests in order to say, what's your risk of prostate cancer as a lifetime risk? And this may also be a very good way to screen for prostate cancer instead of just PSA at an aged base frequency. So instead of saying, hey, you know, we at 40 start PSA screening, we could say, well, we know your genetic risk. And so, you know, Jesse, you get PSA screening.

21:44Wayne, you get colonoscopies. And we kind of risk stratify your prostate cancer risk versus other cancer risks and intensify some people's screening, de-intensify others. So that's those are hopefully things that we'll kind of get into later with with continued research. Yeah. Wow. Amazing. So then let's talk about our guy. So you say get an MRI. He has a PyRADS 4. So walk us through biopsies. You've done a lot of work in fusion biopsy. You've done a lot of work in targeted biopsies. And so let's hit to the biopsy part of this. So yeah, so PyRADS 4, guy needs a biopsy. What are his options for biopsies in 2026?

22:30How are you going to target this? Yeah. So there's a lot of different options. So in general, I'm going to start with the guidelines and then we can go into a little bit of my research and how we really do this with high precision. But the guidelines would suggest that you would do a, and this is pretty universal, at least in the European and US guidelines, that you would do a biopsy through the MRI target. And then you would also do what they call systematic. It's like a grid-based biopsy where they put biopsies around the prostate. Now, the biopsies around the prostate do two things. A, they can help with catching cancers that are MRI invisible.

23:14They can also help if there's some registration. Like, you know, we've all played darts and not everyone hits a bullseye. And so if you are aiming at the bullseye and you come a little bit off, but then you throw a couple more darts, you might have a higher chance of hitting that bullseye. Okay, so that it helps with registration error. And those are the main kind of, those are guidelines accepted strategies. There's also two approaches. One approach is you can put an ultrasound in the rectum and pass a needle through the rectum into the prostate. The prostate sits right underneath or right over the rectum.

23:49Using our shoe analogy, it would be as if you stood on a pipe, basically. Put your foot on a pipe, that rectum is the pipe, your shoe is the peripheral zone, and then your foot is the transition zone. And if you had a needle coming up from the pipe, it would hit your foot. But the problem, I know, maybe I shouldn't use that analogy. Jordan's grimacing. I'm just thinking that we need to make a steel shank on our shoes just so guys can walk on pipe. Regardless, it's easy access, right? So it's very easy to do and it's worked for it. That's the technique that's been used for many years. One of the problems, though, is you have to give people pretty high-dose antibiotics if you do it that way, because there's fecal material in the colon.

24:35You can do fecal cleanses and stuff like that to try and reduce the bacterial load, but you really do need to give pretty powerful antibiotics in order to prevent an infection in the prostate and sometimes the infection going to the other parts of the body. And despite our best efforts, that still happens about 4 % of the time. And so that's one of the major risks of that style of biopsy. So there's another style of biopsy that has gained traction recently where you actually just go through the skin. People are placed in the birthing position. We call it lithotomy, but it's the way that females get cervical exams.

25:07And you put the ultrasound in the rectum still because it's a great guide. You can't get closer to the prostate. But then you sterilize the skin and put the needle through the skin. And I know people get very queasy about these needles in this area. It's very sensitive. And I totally understand. And it is something that comfort is really important. And so we use lidocaine that's buffered in order to kind of take the sting out and basically will numb the skin, numb the prostate. And in general, our average pain scores are about a three out of 10 during these biopsies. So I think that guys do very well or oftentimes surprised by how comfortable it is.