Prostate Cancer (Part 2): Diagnosing Without the Panic

15:11Dr. Jesse Mills: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.

15:33Dr. Wayne Brisbane: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. We 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 biopsied. And we 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.

16:11Dr. Wayne Brisbane: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 PI-RADS-3 the other day that you would usually consider PI-RADS-3, you should biopsy 30%. But when we put his calculated values in, his risk was only 6%. And so I said, hey, you know, would you like to defer biopsy or would you like to go to biopsy? 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.

16:45Dr. Wayne Brisbane: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. And 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.

17:28Dr. Wayne Brisbane: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.

18:01Dr. Jesse Mills:Cardio-metabolic is one of the biggest health challenges in the U.S. and evaluating patient risk across multiple conditions requires careful attention. With so many testing options and guidelines, getting a clear picture of patient health can still be a challenge. LabCorp brings clarity. Our cardiometabolic testing solutions support early risk assessment and empower more informed decision-making, so you can focus on what matters most, your patients. Visit LabCorp.com to partner with LabCorp and simplify complex patient profiles. Are you trying to get weight loss support through telehealth, but it feels overwhelming and rushed, check out orderlymeds.com now.

18:38Dr. Jesse Mills:Orderlymeds.com was built to be different. Here, you connect with real doctors who take the time to understand your goals, review your eligibility, and guide you through a plan that's right for you. Orderlymeds provides access to proven GLP-1 medications like semaglutide and terzepatide, including both name brand options and personalized compound versions when appropriate. So you have choices backed by clinical oversight, not guesswork. It's a simpler, more supportive telehealth experience designed around people who want clarity, care, and confidence in their weight loss journey. And your medication is delivered directly to your home in discreet packaging.

19:13Dr. Jesse Mills:So your experience stays private from start to finish. Do your research, ask the right questions, then visit orderlymeds.com slash podcast for an exclusive offer. Again, that's orderlymeds.com slash podcast. Individual results may vary. Not medical advice. Eligibility required. See site for details.

19:56Dr. Wayne Brisbane:Get your tickets Friday at LiveNation.com.

20:00Dr. Jesse Mills:Support for the show comes from Public, the investing platform for those who take it seriously. On Public, you can build a multi-asset portfolio of stocks, bonds, options, crypto, and now generated assets, which allow you to turn any idea into an investable index with AI. It all starts with your prompt. From renewable energy companies with high free cash flow to semiconductor suppliers growing revenue over 20 % year over year, you can literally type any prompt and put the AI to work. It screens thousands of stocks, builds a one-of-a-kind index, and lets you backtest it against the S &P 500. Then you can invest in a few clicks.

20:32Dr. Jesse Mills:Generated assets are like ETFs with infinite possibilities, completely customizable and based on your thesis, not someone else's. Go to public.com slash podcast and earn an uncapped 1 % bonus when you transfer your portfolio. That's public.com slash podcast. Paid for by Public Investing. Brokered services by Open to the Public Investing, Inc., member FINRA, and SIPC. Advisory services by Public Advisors, LLC, SEC Registered Advisor. Generated assets is an interactive analysis tool. Output is for informational purposes only and is not an investment recommendation or advice. Complete disclosures available at public.com slash disclosures.

21:09Dr. Jesse Mills:How 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 a bag of cash and I want to do an MRI plus your urinary biomarkers. Is that a thing? Or 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 are fascinating. It's a huge ethical debate as well as a cost debate. But, you know, people have money and they don't want to get prostate cancer. What is the diagnostic accuracy of somebody with an incredibly low PSA going through that next step?

21:48Yeah.

21:48Dr. Wayne Brisbane: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.

22:30Dr. Wayne Brisbane:If 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, different tissues in the body have different responses to magnets.

23:12Dr. Wayne Brisbane:And 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.

23:49Dr. Wayne Brisbane:We 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, a kind of clinical trial in England called TRANSFORM, 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.

24:23Dr. Wayne Brisbane:So 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.

24:48Dr. Wayne Brisbane:How do I be very careful? And so we'll just, we'll 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, um, in, instead of just PSA at an aged base frequency. So instead of saying, Hey, you know, we at 40 start PSA screening, um, we could say, well, we know your genetic risk. And so, you know, Jesse, you get PSA screening, Wayne, 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.

25:35Dr. Wayne Brisbane:So that's, those are hopefully things that we'll kind of get into later with continued research.

25:42Dr. Jesse Mills:Yeah. Wow. Amazing. So then let's talk about our guy. So you say get an MRI. He has a PyRADS 4. yep so walk walk us through fusion walk us through biopsies i want to you know 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 walk so pyraz4 guy needs a biopsy what are his options for biopsies in 2026 how are you gonna how are you gonna target this yeah so um there's a lot of different

26:14Dr. Wayne Brisbane:options so in general i'm gonna start with the guidelines and then we can go into a little bit of my research in 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. They can also help if there's some registration, like we've all played darts and not everyone hits a bullseye.

27:01Dr. Wayne Brisbane: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, um, uh, 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 using our shoe analogy. It would be as if you, if you stood on, um, 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 again jordan's grimacing i'm just thinking that we we need to make a steel shank on our yeah yeah right exactly shoes just so guys can walk on regardless um that's the it's it's easy access right so it's it's very easy to do and it's worked for it that's the the technique that's been used for many years.

28:09Dr. Wayne Brisbane:One of the problems though is you have to give people pretty high dose antibiotics if you do it that way because there's, you know, there's fecal material in the colon. You 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.

28:42Dr. Wayne Brisbane:People are placed in the birthing position. We call it lithotomy, but it's the way that females get cervical exams. And 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.

29:20Dr. Wayne Brisbane:So I think that guys do very well or oftentimes surprised by how comfortable it is. It's nothing that you'd sign up for on vacation, but it's actually pretty reasonable. So I prefer the transperineal technique for multiple reasons, but you should know there's two techniques and they're still both highly valid. But my my strong preference is for the transperineal technique. Now, when we get into biopsy strategy, a lot of my patients want to know, do I need those extra cores? Like I get it. Put put needles through this MRI target. But do you need to put cores everywhere? That seems a little nuts.

29:56Dr. Wayne Brisbane:And the answer is no, you don't necessarily need to put cores everywhere. So we have published that if I can use a specialized ultrasound, this micro ultrasound, and I can visualize the spot that the MRI saw, we have a 97 % chance of diagnosing cancer where there's cancer to be diagnosed. Okay. So this was guys who got all the biopsies. We looked at our accuracy at the level of the lesion. And basically, we always found that the cancer almost always. Now, that said, if I can't see the micro ultrasound on micro ultrasound, the same thing that the MRI sees, the accuracy falls apart completely. And so that's a place where the systematic cores can be very beneficial because there's something on the MRI, maybe it's inflammation or something like that.

30:37Dr. Wayne Brisbane:But the PSA as a risk feature may also be signaling cancer somewhere else and the MRI found some inflammation. And I know that's a little bit complicated, but we're using now in clinical trials PSMA, which is a brand new PET scan. and we can get into PET scan if you like, but that's another good test to add on over a biomarker positive, meaning the PSA or the urine test is positive, MRI equivocal or negative. PSMA can be a very strong way to go and delineate who has prostate cancer or not, but that's at the level of clinical trials. So we have about two to three clinical trials in that space using PSMA to guide biopsy.

31:17Dr. Wayne Brisbane:But anyway, all that to say is if you can easily visualize the spot on two imaging modalities, MRI and micro ultrasound or MRI and PSMA, it's very likely to be prostate cancer in that location. You probably don't need the cores everywhere. However, if there's any equivocalness to that, then systematic cores can be very useful. And if you're interested in focal therapy, where we just go and ablate one spot in the prostate, then the systematic biopsies at this current time are very useful to rule out other cancers that are currently invisible in the MRI, but could grow fairly shortly after you do an ablation.

31:55Dr. Wayne Brisbane:And so those are the indications.

31:57Dr. Jesse Mills:I was going to say, I mean, that, you know, prostate cancer is not like other cancers in terms of, as we, you know, we'll talk about grading and staging, but, but yeah, I would think that even if, because otherwise, if you had an MRI targeted lesion, you could just do one biopsy, right? And say, and I mean, he could, you can't really frozen section prostate cancer either. Cause the mitotic figures, it's not, you know, the pathologic diagnosis isn't like taking out of the suite or doing Mohs surgery or something you need, you need it to be fixed. But at least if you have a smoking gun on the MRI, you do one biopsy, you decrease the morbidity, but then you've sort of ruled out doing anything more focal.

32:36Dr. Jesse Mills:If you miss, if you miss smaller cancers elsewhere. So that puts us back into basically, yeah, this guy's got a really bad prostate cancer. He's going to need definitive therapy, surgery, radiation, plus minus hormones. That's a different beast than somebody that may have an obvious lesion. But as we all say in radiology, the most commonly missed lesion is the second one, right? So you don't know if there is something out, if you don't do some kind of sampling. But you're saying you don't routinely do random samples or you do routinely do random samples in addition to the one that obviously lights up on the micro ultrasound or MRI?

33:13Dr. Wayne Brisbane:Yeah, I actually ask guys every time. So we have a conversation about it every time and we chat about it and we discuss kind of what their goals are. It's a long conversation, unfortunately, but you know, that's the UCLA way. We make sure you get what you want. Basically saying, hey, you know, I can get an estimation of how good a person might be for focal therapy, looking at their MRI alone. So I can tell you, Hey, look, this is, this is a possibility for you, or this is not a great option. Um, and then we can decide, you know, where to go from that. Um, and then also we can, um, and some guys, you know, I, we can, with the transparent meal technique, if you have to be on a blood thinner, we can actually do the biopsy still while on the blood thinner, cause the, the soft tissue compresses against the prostate.

33:57Dr. Wayne Brisbane:Um, and that happens for some guys. Um, and so we can do targeted only biopsies. Some guys just don't like the idea of the biopsies and just the fewer cores, the better. And I think we can accommodate them. And then other guys are on active surveillance for low risk prostate cancer. And we're doing some serial biopsies. Maybe the MRI has changed a bit. And my personal opinion, this is starting to get into the point where people disagree. So you need to know that, obviously, for the listeners. But my personal opinion is if we have a good established diagnosis and everything seems to be in one spot.

34:31Dr. Wayne Brisbane:We don't need to go and put cores everywhere. We can just go back to the spot and take a single or one to three samples just to evaluate for upgrading.

34:52Dr. Jesse Mills:Cardiometabolic is one of the biggest health challenges in the U.S., and evaluating patient risk across multiple conditions requires careful attention. With so many testing options and guidelines, getting a clear picture of patient health can still be a challenge. LabCorp brings clarity. Our cardiometabolic testing solutions support early risk assessment and empower more informed decision making so you can focus on what matters most, your patients. Visit labcorp.com to partner with LabCorp and simplify complex patient profiles. Are you trying to get weight less support through telehealth, but it feels overwhelming and rushed.

35:27Dr. Jesse Mills:Check out orderlymeds.com now. Orderlymeds.com was built to be different. Here, you connect with real doctors who take the time to understand your goals, review your eligibility, and guide you through a plan that's right for you. Orderlymeds provides access to proven GLP-1 medications like semaglutide and terzepatide, including both name brand options and personalized compound versions when appropriate. So you have choices backed by clinical oversight, not guesswork. It's a simpler, more supportive telehealth experience designed around people who want clarity, care, and confidence in their weight loss journey.

36:01Dr. Jesse Mills:And your medication is delivered directly to your home in discreet packaging. So your experience stays private from start to finish. Do your research. Ask the right questions. Then visit orderlymeds.com slash podcast for an exclusive offer. Again, that's orderlymeds.com slash podcast.

36:22Dr. Wayne Brisbane:Hey everybody, I'm Bobby Bones. Today we're talking about Thomas Rhett and the Soundtrack to Life Tour. For over a decade, Thomas Rhett has delivered more than 20 number one hits and sold out tours. Inspired by his family and his Nashville roots, he's created songs that have become the soundtrack to our lives. From Die a Happy Man to Life Changes, you've heard his songs playing at life's special moments. Now it's time to hear them live. Round up your friends to catch Thomas Rhett on the Soundtrack to Life Tour. Get your tickets Friday at LiveNation.com.

36:50Dr. Jesse Mills:Support for the show comes from Public, the investing platform for those who take it seriously. On Public, you can build a multi-asset portfolio of stocks, bonds, options, crypto, and now generated assets, which allow you to turn any idea into an investable index with AI. It all starts with your prompt. From renewable energy companies with high free cash flow to semiconductor suppliers growing revenue over 20 % year over year, you can literally type any prompt and put the AI to work. It screens thousands of stocks, builds a one-of-a-kind index, and lets you backtest it against the S &P 500. Then you can invest in a few clicks.

37:23Dr. Jesse Mills:Generated assets are like ETFs with infinite possibilities, completely customizable and based on your thesis, not someone else's. Go to public.com slash podcast and earn an uncapped 1 % bonus when you transfer your portfolio. That's public.com slash podcast. Paid for by Public Investing. Brokered services by Open to the Public Investing, Inc., member FINRA, and SIPC. Advisory services by Public Advisors, LLC, SEC Registered Advisor. Generated assets is an interactive analysis tool. Output is for informational purposes only and is not an investment recommendation or advice. Complete disclosures available at public.com slash disclosures.

37:59Right.

38:00Dr. Jesse Mills:And I mean, you base that a little bit on the fact that as we talked about, you almost always have time with prostate cancer. that if something is equivocal, you can come back in a year, even six months, but most likely a year and relook at that spot. And your targeting is so good now with MRI micro ultrasound that you know exactly where you're looking. It's not a needle in a haystack anymore. You've got a really good image. You got your beads on this to know exactly where you're going to go next year.

38:28Dr. Wayne Brisbane:Right.

38:29Dr. Jesse Mills:Correct. Yeah. Well, let's talk about our guy. So you do the perineal biopsy. He does fine with it. He's like, yeah, Wayne, that was nowhere near as bad as I thought it was going to be. And didn't have a lot of blood in the urine afterwards, had no infection. And you call him and you say, hey, so just want to let you know, we know we did find prostate cancer. You have a Gleason grade 3 plus 4, and we found it in two areas of your prostate, two foci, as we say. The MRI, we knew ahead of time, it showed that the prostate looks like it's confined to the organ itself. It is not spread into surrounding organs such as seminal vesicles or rectal wall.

39:09Dr. Jesse Mills:And there's no extra capsular extent. And I'll actually say this. Maybe this guy, because in this day and age, a lot of times patients get their medical information uploaded before we even get to make that phone call. Right. That's one of the things that we fight with as doctors is that that I may have opened up my chart and said, oh, it says here I've got two foci of three plus four disease involving 20 percent of each core. MRI shows organ confined. What is what did what just happened to me? Tell me, first of all, is this guy going to be OK? Are we going to be OK with what I just said? Is this a don't buy green banana situation or or is this guy have a lot of daylight and sunsets ahead of him?

39:47Dr. Wayne Brisbane:Yeah. Yeah. Great question. So this gets into the flavors of prostate cancer. So every cancer, regardless, prostate cancer is no exception, kind of goes through these phases. The first is screening, then diagnosis, then risk stratification, then treatment, then survivorship. Okay. So you have these five phases to every single cancer. It may look different depending on what the cancer is, but we went through screening. We've now gone through diagnosis. The next step is actually not treatment. It's risk stratification. So there's definitely multiple different types of prostate cancer. And we need to risk stratify his prostate cancer because that directly informs how we treat it.

40:33Dr. Wayne Brisbane:Then is going to be diagnosis and then is going to be the survivorship. So intermediate risk prostate cancer. That's what we're talking about. And I'm going to unpack that so we know exactly what it is. there's multiple different ways of looking at the prostate cancer. The main one though, is under the microscope. So you have a pathologist and they look at the cells and they're going to look at the cells as a pattern. Okay. So they'll, and they'll give one of two scores. Oftentimes they'll give both. The first has been around for more than 50 years. It's called the Gleason score. And a lot of people have heard of that.

41:04Dr. Wayne Brisbane:The second one is called the grade group. Um, and that is a way that was initially intended to simplify the Gleason score, but now we just report both to make it more confusing. So it's, it's been, it's been, it's anyway, but it's a, it's a good idea.

41:18Dr. Jesse Mills:The Gleason lobby is very strong.

41:20Dr. Wayne Brisbane:So what I'll tell you is I think about this, actually your, your marathon example is, is a pretty good one. And so I think of this as the pathologist is looking at the, through the microscope. If you've ever seen one of those aerial photos of a bunch of people running in a marathon, you can, you can get an idea of what the pathologist is looking at. Now, these aerial photos are static, but you can, I, you can tell if they're at the start, nobody's moving. If they're mid race, people are, they're running or if they're at the finish line and they're sprinting. Okay. And that's based on body position might be based on the distribution of the people who are in the picture.

42:06Dr. Wayne Brisbane:But actually, if you showed pictures like that to all three of us, we've come up with reasonable kind of assessments of those phases of the race. And the pathologist is doing something very similar. They're looking at the cells. They're looking at specific features in the cells, which we won't get into. But they're saying, are those cells walking, running, or sprinting? They're trying to say, how fast are these cells moving? and it's a static image, but we can interpret based on cellular features what the speed of movement is. And within cancer, just to use our car example, that's how fast is the gas pedal pressed down.

42:42Okay.

42:42Dr. Wayne Brisbane:So how fast is the cell moving? And when we talk in cancer, that's called a grade. Okay. We're going to also talk about stage. That's how far the cancer has traveled. So how fast it's moving versus how far it's traveled. You can have a moderately fast tumor, that's had a lot of time to move, or you can have a very fast cancer that hasn't had a chance to move, and those are treated very differently. So grade and stage are very important for the risk stratification of the tumor. Now, in general, there's five different grades. When Dr. Gleason first developed this score, grade one was normal. Grade two was low-risk cancer.

43:22Dr. Wayne Brisbane:Grade three was moderate-risk cancer. Grade four was bad cancer, and grade five was terrible, okay? But over time, we've said grade one is normal grade two is actually normal okay so this was one of the developments over time where the pathologists have made changes so grade two is actually normal so when you get your pathology back and let's say we took more cores than just the ones in the target there'd be a lot of ones that say benign is when you get your your path back and those would be great gleason scores one and two now if the cells look like they're walking that would be Gleason pattern three.

43:59Dr. Wayne Brisbane:If the cells look that they're running, that would be Gleason pattern four. And if the cells look like they're sprinting, that would be Gleason pattern five. And the pathologist will say, you know, if you take a picture of this race, you'd be able to see that not everyone's moving at the same speed as maybe, maybe you're more of a Gleason pattern three and your son was a Gleason pattern four. But yeah, that's exactly right.

44:20Dr. Jesse Mills:I was hoping 3.5.

44:24Dr. Wayne Brisbane:but um you're going to say you know you're going to see in this population of cells or people in our race analogy there's different speeds and so we we can't say well this is all gleason pattern three or all gleason pattern four so we'll give you a ratio we're going to say you're a three with some four and then the pathologists will oftentimes say that's five percent pattern four so five percent runners maybe 30 percent runners when you get up to 50 percent or beyond so if it's 60 % runners, they switch the numbers. So it becomes four plus three rather than three plus four. And that is how the Gleason score gives you a ratio.

44:58Dr. Wayne Brisbane:Now there's some inherent problems with the ratio. For example, if you have two to three runners and not that many walkers, then it might be four plus three. But if you have a ton of runners, but you just have a ton of walkers as well, it might be three plus four. So the score breaks down in some ways, but this is the most commonly diagnosed score a pattern three plus four in the MRI era. Okay. Now that we've stopped doing just biopsies as a, as a trigger, um, Gleason pattern five is very dangerous. It's one of the, the cancers that really do cause a lot of problems, but thankfully very rare. Okay.

45:33Dr. Wayne Brisbane:And if you have cancers that are only runners pattern four plus four and a large amount of them, when the pathologist reports out, they say there's a lot here, a lot of running patients. Those are very dangerous as well. this three plus four and four plus three are the ones that are often diagnosed. They're often curable. They're a high enough grade that we consider them treatable in men, especially men who are in their fifties, where we'd say, Hey, you know, these will, if we give them enough time, it may be several years, but if we give them enough time, they would spread. And so we would want to treat these before they had the opportunity to spread.

46:06Dr. Wayne Brisbane:And so that's kind of where I would, I would kind of talk to you or this 55 year old and kind of explain those. That's where we get the Gleason score. Now, I'll pause there because I have a couple more things to say, but that's a big soliloquy. So any questions that generated?

46:21Dr. Jesse Mills:I think we're following, and I think the main idea here is that that risk stratification is critical. I guess the only question I have, which is sort of a loaded question because I know the answer, but then if you have any pattern of four, why would you report out the three, right? I mean, I get a four plus three, but if you have with three plus four, why don't you just say four? Because the threes, those guys walking, they're not going to make the finish line any time in my lifetime.

46:48Dr. Wayne Brisbane:Yeah. Great, great question. So actually there's a, there's a big move to do that. So the, so there's a group that's led out of Memorial Sloan Kettering and actually UCLA is one of the, one of the sites as well. But this idea of where let's, let's not report out the pattern three, let's just report out the volume of pattern four. Obviously, if there's pattern five, we need to report that out. But instead of just pattern three, we need to report out the volume of pattern four. And this gets to historical context. We've been using three plus four and four plus three and four plus four, all these kind of ratio-based patterns for decades.

47:25Dr. Wayne Brisbane:And so it's very entrenched within the way that we do things in medicine. And it also works really well. So we've been using this for risk stratification for decades. It seems to work very well. We can probably tweak it and make it better. But obviously, we want to study this to make sure that we're doing the right thing. And I think that this will be future research. The other thing that we can do, though, is we can look at other biomarkers for speed of running. So let's say we take our race analogy and you take a picture of a bunch of runners and it's all three plus three, right? This is the start of the race.

48:04Dr. Wayne Brisbane:It's all three plus three. Obviously, we know some of those runners are going to do really well and some are not. But how do we know at the beginning of the race? Well, we can, probably extending this analogy too far, but we'll give it a try. We can look at their training schedule, okay? So we can say who's been training really well and who hasn't. And the way that we do that is we look at some kind of a genomic RNA test. There's three different ones, but we can basically use an RNA, which is the messenger molecule between DNA and protein. And it's a, the reason we use RNA is it's, it's a tumor specific and it can be encoded pretty easily.

48:41Dr. Wayne Brisbane:We can, we can interpret it pretty easily. Um, and we can compare the RNA of this gentleman's tumor, our 55 year old male, who's in my office to a bunch of other gentlemen who we know what happened to them over 15 years. So we can compare his RNA to their RNA. And we can say, is there any difference between them? Does his race schedule, does his training, does his tumor look like it's going to be a runner or look like it's going to be a walker over the next 15 years? And we can use that to help us understand what direction should we go with your treatment? Should we be more aggressive? Should we be more conservative?

49:17Dr. Wayne Brisbane:It's not perfect, obviously. You could have somebody who trains really well and sprained their ankle. But it's a very, it's a nice way of having additional information about the characteristics of the tumor. And it becomes really helpful in this three plus four cancers where you have some runners. It's probably not going to be, you know, there's a lot of race left to live, but we can get an idea of how the cancer may behave over the next few years and possibly start to recommend more things like active surveillance, which will, this is starting now, we've done our risk stratification, we're moving to treatment, active surveillance versus one of these active therapies.

49:53Dr. Jesse Mills:Yeah, that's amazing. I mean, so I think that the take home is that once you get the diagnosis, that risk stratification is so critical to know what you do with all those data. And the RNA markers even give you a little bit better idea of, you know, we talk about the wolf in sheep's clothing and there are people that look as if they have a Gleason for maybe a low grade, I mean, intermediate grade, but actually have something much more aggressive hiding in their genes. And I think that 15-year window is critical as well, because, you know, if I'm not 55, if I'm 70, you may have a different conversation with me than if I'm 55 with that exact same tumor diagnosis, same genetics, same everything else.

50:40Dr. Jesse Mills:But as you say, to make a morbid finish line metaphor, is that the prostate cancer going to win the race and kill you? Or is something else, either another malignancy, as you talked about earlier, in terms of risk stratifying versus colon cancer risk, prostate cancer risk? Or how's your heart? How are your lungs? How's your weight? What's your diabetes risk? I mean, what are the other, there's one of the things that's really important is to treat men holistically. And sometimes in the world of oncology, they get an undeserved bad rap for thinking their goal is to save you from cancer and not, you know, think about other organs.

51:19Dr. Jesse Mills:In fact, we do a really good job these days of risk ratification based on overall survivability and some actuarial numbers to just say, okay, look, you know, you're 75. In fact, these days, we rarely even screen men over 75 for prostate cancer because if they haven't gotten a clinically significant cancer at that point, something else is going to beat the cancer to the finish line.

51:45Dr. Wayne Brisbane:Yeah, okay.

51:46Dr. Jesse Mills:Yeah. Well, wow. So we've got diagnosis. I mean, I think, Jordan, what are we missing from your notes? Anything else that we need, Dr. Brisbane, to talk about with a diagnosis of prostate cancer?

51:57Dr. Wayne Brisbane:I mean, you hit most of them. And what I have isn't really a full-fledged question, but the thing that sort of surprised me the most in hearing everything you had to say was, as you said, how treatable this is. I mean, I guess my question is you sit down and you give this diagnosis to someone, they hear cancer, and that's kind of probably the only word they hear for the first, you know. But, I mean, what would you say? Obviously, it's a case-by-case basis and everybody's different and everybody's circumstances are different. But I mean, just to end on kind of a more positive note, other than the morbid finish line analogy, what would you say to those people in terms of how treatable this is?

52:39Dr. Wayne Brisbane:This is a very curable disease for many, many men, especially if it's caught early. And it can be something that sometimes we need to do treatment, but it's very curable.

52:51Dr. Jesse Mills:So this guy is going to be okay.

52:52Dr. Wayne Brisbane:Yeah, he's going to be definitely okay.

52:54Dr. Jesse Mills:Three plus four, he'll be back in the gym. And let me ask you this. I mean, we're going to have a whole next segment on treatment, but can that guy go back on testosterone?

53:03Dr. Wayne Brisbane:Yeah, we oftentimes can get them back on testosterone. Sometimes there's some nuance to it, but the answer is absolutely. Great, great.

53:11Dr. Jesse Mills:Because it's good for more than just sexual function, as we've talked about multiple times on the show, as a big part of my research, of course, in men's health is where hypogonasm plays a role. But you're right. It's great for bone density, great for cardiovascular improvements, et cetera. So Wayne, you've done it all so far. I really appreciate all of your professorial explanations, your metaphors from cars to marathons, maybe still a little to fashion. To footwear. I mean, you coined an idea. It's going to be at the top of leisure wear for spring break and cruises now in April of this year.

53:48Dr. Jesse Mills:But I appreciate so much. I'm looking forward to having you back here in a little bit to talk about how we treat this man with what sounds like a very curable disease if caught early. Wayne Brisbane, professor at UCLA of urology, surgeon scientist extraordinaire. Thanks so much. Long transit. Let's take us out on that guitar riff. Jordan, I'll see you soon.

54:21Dr. Jesse Mills:Let's talk about it in the mailroom

54:26Dr. Wayne Brisbane:Let's talk about it Let's talk about it in the mailroom Let's talk about it Let's talk about it in the mailroom The Mailroom with Dr. Jesse Mills was a production of iHeartRadio. It was executive produced by Jordan Runtag.

54:48Dr. Jesse Mills:It was edited, mixed, and mastered by Bahid Frazier, and the theme was provided by Long Transit. If you liked what you heard, please subscribe and leave a review. For more podcasts from iHeartRadio, check out the iHeartRadio app, Apple Podcasts, or wherever you listen to your favorite shows. This program is intended for educational and informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.

55:16Dr. Wayne Brisbane:Consult your health care provider for any medical or other related questions or concerns. The views and discussions aired on this podcast are those of Dr. Mills and do not represent the official positions of UCLA or UCLA Health.

55:46Dr. Jesse Mills:Here, you connect with real doctors who take the time to understand your goals, review your eligibility, and guide you through a plan that's right for you. Orderly Meds provides access to proven GLP-1 medications like semaglutide and terzepatide, including both name brand options and personalized compound versions when appropriate. So you have choices backed by clinical oversight, not guesswork. It's a simpler, more supportive telehealth experience designed around people who want clarity, care, and confidence in their weight loss journey. And your medication is delivered directly to your home in discreet packaging.

56:18Dr. Jesse Mills:So your experience stays private from start to finish. Do your research. Ask the right questions. Then visit orderlymeds.com slash podcast for an exclusive offer. Again, that's orderlymeds.com slash podcast. Individual results may vary. Not medical advice. Eligibility required. See site for details. I'm U.S. Transportation Secretary Sean Duffy. We all get distracted when we drive. whether it's from our phones or kids in the backseat bickering. But how we handle these distractions can be a matter of life or death. Before you get on the road for your next road trip, please put your phones on silent and take a mental note to focus on driving.

57:04Dr. Wayne Brisbane:Paid for by NHTSA.

57:07Dr. Jesse Mills:Are you a fraud-paying American? One in four tax-paying Americans has been a victim of identity fraud. With LifeLock, if your identity is stolen, they fix it. Guaranteed or your money back. Last year, billions in refunds were stolen. Could be from your salary, overtime, or second job. Gone. But this year, you don't need to stay a victim. Because this tax season, fraud-paying American is something no American should have to claim. Save up to 40 % your first year. Visit LifeLock.com slash iHeart. Terms apply. This is Jacob Goldstein from What's Your Problem? Business software is expensive. And when you buy software from lots of different companies, it's not only expensive, it gets confusing, slow to use, hard to integrate.

57:51Dr. Jesse Mills:Odoo solves that because all Odoo software is connected on a single affordable platform. Save money without missing out on the features you need. Odoo has no hidden costs and no limit on features or data. Odoo has over 60 apps available for any needs your business might have, all at no additional charge. Everything from websites to sales to inventory to accounting, all linked and talking to each other. Check out Odoo at O-D-O-O dot com. That's O-D-O-O dot com.

58:22Dr. Wayne Brisbane:This is an iHeart Podcast. Guaranteed human.