The Peter Attia Drive - #39 - Ted Schaeffer, M.D., Ph.D.: How to catch, treat, and survive prostate cancer

Episode Date: February 4, 2019

In this episode, Ted Schaeffer, Professor and Chair of the Department of Urology at Northwestern (youngest chairman in the country), presents the roadmap for the best way to screen for, and treat, prostate cancer. We also get into the “mass screening” controversy and all the risks involved with treatment. In addition, we discuss our evolving understanding of cancer and the most exciting areas of research to come.  We discuss: Ted’s unique path to get his PhD [5:15]; The exciting transition in science during Ted’s PhD in the 1990s [15:30]; Ted’s advice to MD-PhD students, and why he choose urology and Johns Hopkins [23:45]; History of prostate surgery, and Pat Walsh’s legendary work in prostate cancer [36:15]; Prostate surgery and the risks involved with treatment [53:00]; Screening for prostate cancer [58:00]; The “mass screening” controversy [1:12:45]; Biopsies and MRI: important things to know [1:25:30]; Why urology such a great field of medicine, and why Peter wants a goat [1:34:45]; Ted’s work with Ben Stiller [1:39:00]; Gleason grading system [1:43:45]; Testosterone, DHT and the prostate cancer controversy [1:53:15]; The metabolism of the prostate [2:03:00]; The most exciting areas of research in prostate cancer [2:08:00]; Benign issues involving the prostate: pelvic pain, infections and treatments [2:11:15]; Video of Ted’s surgeries, the latest technology, and males contraceptive options [2:18:00]; Watches and cars [2:23:30]; and More. Learn more at www.PeterAttiaMD.com Connect with Peter on Facebook | Twitter | Instagram.

Hey everyone, welcome to the Peter Atia Drive. I'm your host, Peter Atia. The drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top performing individuals in the world, and this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information on today's episode and other topics at peteratia-md.com.

Hey everybody, welcome to this week's episode of The Drive. I'd like to take a couple of minutes to talk about why we don't run ads on this podcast and why instead we've chosen to rely entirely on listener support. If you're listening to this, you probably already know, but the two things I care most about, professionally, are how to live longer and how to live better. I have a complete fascination and obsession with this topic. I practice it professionally, and I've seen firsthand how access to information is basically all people

need to make better decisions and improve the quality of their lives. Curating and sharing this knowledge is not easy, and even before starting the podcast, that became clear to me. The sheer volume of material published in this space is overwhelming. I'm fortunate to have a great team that helps me continue learning and sharing this space is overwhelming. I'm fortunate to have a great team that helps me continue learning and sharing this information with you. To take one example, our show notes are in a league of their own. In fact, we now have a full-time person that is dedicated to producing those, and the feedback has mirrored this. So all of this raises a natural question. How will we continue to fund the work necessary to support this?

As you probably know, the tried and true way to do this is to sell ads, but after a lot of contemplation, that model just doesn't feel right to me for a few reasons. Now, the first and most important of these is trust. I'm not sure how you could trust me if I'm telling you about something when you know I'm being paid by the company that makes it to tell you about it. Another reason selling ads doesn't feel right to me is because I just know myself, I have a really hard time advocating for something that I'm not absolutely nuts for. So if I don't feel that way about something, I don't know how I can talk about it enthusiastically. So instead of selling ads, I've chosen to do what a handful of others have proved can work

over time. And that is to create a subscriber support model for my audience. This keeps my relationship with you, both simple and honest. If you value what I'm doing, you can become a member and support us at whatever level works for you. In exchange, you'll get the benefits above and beyond what's available for free. It's that simple. It's my goal to ensure that no matter what level you choose to support us at, you will

get back more than you give. So for example, members will receive full access to the exclusive show notes, including other things that we plan to build upon, such as the downloadable transcripts for each episode. These are useful beyond just the podcast, especially given the technical nature of many of our shows. Members also get exclusive access to listen to and participate in the regular Ask Me Anything episodes. That means asking questions directly into the AMA portal and also getting to hear these

podcasts when they come out. Lastly, and this is something I'm really excited about, I want my supporters to get the best deals possible on the products that I love. And as I said, we're not taking ad dollars from anyone, but instead, what I'd like to do is work with companies who make the products that I already love and would already talk about for free,

and have them pass savings on to you. Again the podcast will remain free to all, but my hope is that many of you will find enough value in one, the podcast itself, and two, the additional content exclusive for members to support us at a level that makes sense for you. I want to thank you for taking a moment to listen to this. If you learn from and find value in the content I produce, please consider supporting us directly by signing up from monthly subscription. My guest this week is Dr. Ted Schaefer, the chairman of urology at Northwestern University

in Chicago. He's a urologist who specializes in the diagnosis and treatment of prostate cancer. His high quality work has earned him the trust of people like Ben Stiller, who he's operated on and who have spoken very publicly about his own battle with prostate cancer. In this episode, we go through all of the current and basic best practices for the screening and treatment of prostate cancer from the latest drugs to the surgical options.

The conversation naturally leads to our evolving understanding of cancer and the most exciting areas of research in prostate cancer specifically. We also touch on the controversy around the role of things like testosterone replacement, in the development of prostate cancer, and even the controversy surrounding prostate screening using things like the PSA. And finally, if you're an MD PhD student, which I realize might not be many of you, you'll want to listen closely as Ted has some of the most pertinent and I, in my opinion, most important advice for those who are deciding on how to

Thread this needle of being clinicians and scientists. So without further delay, Please enjoy my conversation with one of my closest friends from residency, Dr. Ted Schaefer. Hey, man. how are you? I'm great, good to see you. Dude, it's kind of weird when I go and visit my friends from residency and I see them in their grown up clothes and their grown up offices. It kind of makes me feel like I failed.

Well, your office is stunning. The view over the lake in Chicago, and admittedly, this might be the best month of the year to be in Chicago But it's like we're in the elevator coming up here, and I'm I Feeling we're supposed to be goofing off like we always did and I'm like wait. We can't goof off He's now the chairman of yourology. We got it. We got to be serious. It's true when I look at him looking at you You're doing this recording and I can't help but just chocolate So we'll get to all the med school stuff or the residency stuff

because that's obviously where we met. But let's talk a little bit about your decision to even do a PhD and you know you have kind of an interesting story there because you weren't on the typical MD PhD path right? Yeah I you know people ask me about my life and how I got to where I am and there's a couple of principles I think about. And there are common themes that we share together. But one of the things I teach are talk to my trainees about is, you know, you never walk by an open door without looking inside. And so that's how I ended up being at the NIH, doing my PhD. But even before that, I think the way my brain was built was that I always wanted

to see what was inside the open door, inside the alarm clock, inside the watch. And so conceptually, as I moved through my training, my light biology, because I wanted to understand how things worked. I loved organic chemistry. I loved putting the puzzles together, making things happen. And so as an extension of that, when you're in medical school and you're learning about the pathology of why things fail, understanding that at a cellular level just always appealed to me. And I loved the ICU. I loved the physiology of the human body and how you can measure all that. And so I think about that a lot,

because I read and been following your blogs and your life and how you analyze everything you do. And so for me in medical school was a lunchtime thing. I went by this open door and there was this opportunity to apply for a scholarship through Howard Hughes Medical Institution to really go study science at the NIH. And I had started college and school early early so I had about, I felt like I had a year to kind of play around and see what was interesting to me. And it was something

that was out of the box for me, but I just, you know, when you find something that makes sense, it's no longer risky to you. You're not exposing yourself to anything. It's really just exploration. And so that, that came very natural because I'm not the type of person who likes to take on risk, do different things. But for me, it wasn't a risk to just leave medical school and go to the NIH, it was an opportunity. When you were in college, did you know you wanted to go into medical school?

I think so, yeah, I loved biology, I loved understanding the way things were and how they worked. The most complex of all those things is the human body and just a living organism, a multicellular organism is just incredibly fascinating to me. I was always attracted to that. I thought that was a natural extension of it. I remember when I was in college, there was a very famous anthropologist at University

of Chicago who was one of these dinosaur hunters. And so I just, you know, I loved, I loved the idea of just discovery and I loved that idea of anatomy and discovering what dinosaurs were like and how they did that. I remember I talked to my father who's a physician and I said, you know, I think I wanna go off to grad school

and be an anthropologist and he's like, you're going to do what? You know, but that concept of discovery, innovation, figuring things out, it's just something I've always had in me. So you don't just go to NIH. How did you wind up in the lab of a Nobel laureate? Well, it was through a friend of mine. So when this program I was in, you know, you went and you interviewed in different labs and you basically decided what you wanted to do.

And some people, it was an incredibly talented group is about 40 medical students from all over the country. So some of these people, they're just amazing. They knew what they wanted to do. They knew what field, who they wanted to work with and so forth. I wasn't sure what I wanted to do, they knew what field, who they wanted to work with, and so forth. I wasn't sure what I wanted to do. I knew I wanted to pursue this idea of discovery

and pursue it at a high level. And I remember there's a guy named Jonathan Ashwell, he was an immunologist, and I thought, well, maybe I should do immunology, mostly because I didn't really understand immunology very well for my medical school class. It was a weak kind of class for me. So I went and talked to him and he said,

you know, he's a really tough guy, very successful, hardcore scientist. And at the NIH, immunology there was just really, really, you know, just amazing. And he said, listen, you just got to pick a guy, he was really tough. He just said, look, just kind of man up,

pick something and you'll get into it and you'll love it. And I thought, you know, that was actually good advice, you know? And so I was shopping around for somebody who was motivated, who was driven and who was smart to work with. And a good friend of mine, who's actually here at Northwestern Grand Baruch, you should look at this, go talk to this woman, Pam Swartzberg, she's a postdoc in the Varmas Lab

and she's looking for a student and she's really good. And so I went interviewed with her and she was exactly what I wanted. She's brilliant scientist and she happened to be in the Varmas lab. But, you know, the Varmas lab was a bunch of postdocs who would be effectively associate her full professors at any other university. They were just incredibly smart people. And I got to, you know, these individuals are just amazing. So I met her and then worked through her with him.

And the plan was always to, she had already been offered a position as a researcher at the NIH and she was waiting to transition to her own lab. So we, yes, technically I was a varmous lab member for six or nine months. And but all along I was mentored by this woman, Pam Swarthberg, who was just a brilliant scientist. And when she was a tech in her lab at Columbia, she was making, you know, she was had covers of cell, you know, she was just brilliant. So Harold attracted people like this in his lab group.

And we stayed part of his lab group, and we stayed part of his lab group, although independent throughout my kind of experience there, and I always considered our group to be equal, but part of his group. So it was a lot of fun to interact with him on a weekly basis during lab meetings, just to see how he thought, I mean, you know, like you, I like to surround myself with people who are just incredibly smart. And by being a member of his lab team, I by default did that, not just him, but many, many other people. So it was really fun. For the listener, of course, Harold Varmison and Michael Bishop shared the Nobel Prize probably in the late 80s or early 90s. It was like 88, 89, 90, something like that, right? They basically were the first people to elucidate the relationship

between viruses and oncogenes. Is that correct? Yeah. So the concept of their prize was, and I'll probably butcher this, and the real scientist out there will kill me for it. But the idea was that they described that you could pass on a cancer through a viral induction. So these viral oncogenes was what they described.

So they were an active alteration in the cell's normal machinery to induce a cancer. You know, I've never met Harold, but I did have the privilege of having dinner with Michael Bishop once a few years ago. And it was a very intimate, you know, there's like four people there, but everyone was either a Nobel laureate or will be a Nobel laureate sort of thing, you know, Luke Cantley, David Sabatini, Michael Bishop. And you know, it's just one of those nights, like you don't want it to end. You can't believe that, you know,

because we were at a stake house and we were sort of sequestered in our own little room and we probably spent like five hours there just talking about their work. It was amazing. You said something a second ago that I love, I didn't know this about you actually. So this is the fun thing of interviewing your best boys

is you still learn something. Part of the reason you retracted immunology is you felt it was a weakness. And having spoken with a number of very good scientists, I find that to be a very common thread. The great ones seem to go towards their weaknesses rather than away from them. Steve Rosenberg, who was my mentor at the NCI, I always talked about the reason he did. He always knew he wanted to be an immunologist, always, non-negotiable. But he did his PhD in biophysics, because he didn't want to be intimidated by these differential equations when he read papers. He really wanted to understand

a field of science that didn't come, you know, sort of easily to him. So that's sort of an interesting aside about you. Yeah, I was funny. I had a great mentor and worked hard. And, you know, on paper, I had a great PhD. And I remember, was degree granted through the University of Chicago. So again, I wasn't in a formal PhD program. There was an open door for me to do this great, you know, this great program and opportunity. And I went there for a year. I just loved it.

I loved the research environment. And from there, I petitioned to stay an additional year. And I didn't really know what it meant to have a PhD. I mean, I wasn't going there for a PhD. I was going there to do science. But I had friends that were in formal MD PhD programs at University of Chicago. And they were like, man, what you've done

is PhD students would die for. And I was like, well, I don't know, I'm just doing my thing. So at that time, I was an idiot, and I was kind of balsy. So I wrote a letter to my dean, and I said, well, I think I should be, I should be, someone should give me a PhD for this stuff. And they said, well, why don't you fly back and why don't you give us a talk. And I did. And they're like, okay, yeah, you do know what you're talking about. And what you had published, you have actually a very similar story to another good friend of mine who, you know, was in a

similar situation where he basically was in the right place at the right time, right? It was in a great lab, very well mentored, great project, and was willing to go to the wall for it and ends up getting a first authorship in science and nature. And it's sort of like, you just have to hand those in and that becomes a PhD. That's the idea.

And so, yes, all the critical thinking and how to develop and come up with on a hypothesis and test it, I did all those things. So I mean, I met all the formal thinking and how to develop and come up with on a hypothesis and test it. I did all those things. So I mean, I met all the formal criteria for it. I just did it in a, I wasn't in a structured way. It just happened to be in a good environment. What was the most interesting question you were asking during your time at NIH? Well, I mean, I think immunology, and really, I think I was more in a cell signaling lab lab and so a lot of what we did was biochemistry and The idea was you know, well you would take a single protein and you'd knock it out or turn it on or whatever and it would have an a

huge effect and I think At that time people were thinking really very linearly, you know, I had to mean, my PhD was pretty much the most amazing experience you can imagine. So on my floor and building 49, it was in the old center. This is before the new middle center was built, which was built. So, but building 49 was a genome institute. It was across the street from the NCI buildings, which I think were 35 and 37 or something like that. So on my floor was Harold Varmas. Varmas lab, I was technically in our own lab with Pam, but we shared the last space with Francis Collins.

So you know, it was just, I mean, you couldn't just pick a better floor to have just people on. And so at that time, Genomics and transcriptomics. And this is the mid 90s. This is 97 to 99. So I mean people are just starting to do homemade microarrays and looking at expression and I remember people would like take a muscle cell and they compared to a fiberglass and they would be like, oh my god, you can see these different expression changes in these homemade

microarrays. And so that's when everything was just taking off. I remember loose doubt who's still at the NIH, who was working on, there was a power of use, student working on lymphomas, and just characterizing the different genomic phenotypes of them, and people still use that stuff today. It's pretty amazing.

And so I was there when all that was happening. I remember when I went there, at University of Chicago, people really weren't on the internet. And then I show up and I go to the lab and there's T1 lines at the NIH and the internet. And I remember downloading the Clinton debacle, you know, and reading that in detail. And so like, there's all these just amazing things that happened in science and happened in technology that were going on at that period of my life and that period in the world. It was pretty

amazing. So the thing that's a long answer to the concept that when I went there, I think people are still focused on single gene, single change. They're still looking for the like, well, you have this mutation, you get this cancer, this mutation, you have this phenotype. And you know, the human body is a polygenetic organism. And so, yeah, at last count, if there's 20,000 human genes, I believe there's something like 73, but I could be wrong. Let's just call it a hundred and roundup. There were about only a hundred disease states that result from single gene representations.

Yeah. Out of 20,000 genes. Yeah, so, you know, that was the big thing, the big transition in Francis Collins is really leading that where there are people hunting for the gene for type 2 diabetes. At the time I was there, and of course now we understand it's a complex equation. And so within immunology, when I was there, it was also a transition. So it turns out that the tyrosine kinases that I worked on in my PhD are really involved

in fine tuning the T cell receptor signaling. They're really reostats. They really fine tune the signal. It's not off-arron, just like, you know, you have a mutation in X, Y, or Z off-arron. And so I think one of the big themes of what was evolving at the time I was there was this concept that was a fine tuning.

And I remember we would do a manology retreats in the road. So another way to explain this maybe for the listener, because of course I hear Riestad and I think about Riestad's because I'm an engineer. Digital is a signal it's on or off. That's right. Zero or one. Analog is like the volume button on your radio. You can go from nothing to full blast, but an infinite number of iterations in between. And that's what you mean by modulating the signal. Right. And I think that that trend that was a period of transition in between. And that's what you mean by modulating the signal. Right. And I think that that trend, that was a period of transition in science,

where maybe we people always thought that that happened, but people were developing the tools to begin to test that and understand that. And you know, think about cancer immunology. And the Rosenberg lab was a huge player on campus when I was there, which was 10 years before you were there. And they were hunting for single tumor antigens, right? But then they were realizing that it's a complicated thing. There's multiple factors that come into the role in the play there. For me, that was maybe conceptually something people had always thought about, but the tools to explore that, the tools to test that on multi-gene levels were kind of coming online

in science at that time. So it's a pretty fun time to do that. Talk a little bit about a tyrosine kinase. I mean, these are so ubiquitous in biology that, and they just come up over and over again. So explain to someone who doesn't understand what that is, what it is, and why it's relevant, and maybe where it shows up. You have your DNA, everybody's born with it. It's in every single cell in your body. But the skin cells in your body make a certain amount of melanin that make you darker than I am.

And so within between different people, there's variability in what the individual cells do with the DNA. And then within the human body, there's different cell types, and they use the DNA, the code differently. That code then is incredibly, it's modified, right, by exposure to the environment, and that's the epigenetic change. And what results is a protein. And so once you have a protein, that's really what kind of constitutes a lot of what's in

our cells in our body. But they're not inert. They're constantly changing. And so one of the ways that they change and one of the ways that the signals change within an individual cell, how the cells communicate with each other, et cetera, is by having kind of temporary modifications to those individual proteins. And so one of the ways that happens is through these kinases. And there's different pieces of the proteins that can be modified. So one of them is a tyrosine kinase, but there are other types of kinases.

And these are temporary modifications that happen within a protein, within a cell to typically transmit a more acute or change within the cell or between two cells and so forth. And of course, these have become a very attractive target for drugs. Yeah.

So one of the, obviously, the idea in cancer biology is to find alterations, to find mutations, to find changes that you can, quote unquote, target to do precision oncology, precision medicine. And so these are one of the ways that we're beginning to think about, you know, advancing the kind of medicine in that special way. Gleevec targets a tyrosine kinase, doesn't it? It does. It targets a specifically altered fused gene.

So it's not just a random tyrosine kinase. It's a tyrosine kinase that's altered by specific mutation within a cancer. I mean, that was how I was originally described. And so, yes, it will target those. I'm going to have a specific effect. And that was, you know, work done on the West Coast. And part by Charles Sawyer who's now a memorial, who's, you know, an idol of mine. But he wasn't the only one involved in kind of identifying these fused mutation. It's sort of one of those exceptions to this rule, right, where

if you have that mutation, which basically is, if I recall, it's only showing up in CML and GI stromaltumers, then you do have the one-hit wonder. You do. This drug is, at least in the CML, it seems curative. I don't recall if it was actually curative in just... GI stromal tumors or if it was just basically could render it a chronic disease. For the GI stromal tumors, it's not my space, but yeah, it works, but there is resistance that develops, I think in both models now, but in general, for the liquid tumors, it's much more durable. And for the GI stromals, it does help to suppress the growth of those tumors. Some of them do recur and come back, and that's the concepts of how we manage and we've converted HIV-H to from a lethal disease to a chronic condition, really.

Those basic principles of multi-targeting of the particular cell. So for cancer, single agent like Levek isn't going to work because the cells change an alter, but doing double or triple targeting will be effective long-term approach for those, just like we've learned from HIV management. So, I'm sure today, you're now the chairman of urology, so you encounter lots of residents and medical students, and if one of them came to you and said, hey, Ted, or I guess they have to call you Dr. Schaefer, but you know, I'm really thinking about doing a PhD. And what advice would you give them to select a good lab?

In other words, you describe so much of your trajectory is the, is you're the beneficiary of having been exceptionally well mentored. And you, you know, you've talked about Pam now and before. And I know we've talked about just when you have an amazing mentor, it's like everything works out. And yet there are countless students who go into labs that just couldn't waste more time. They don't actually learn how to think properly. They come out as dumb as they were when they went in and the field is not advanced.

So in as much as surrounding yourself by the right people is the best first step you can take, what guidance would you give somebody to, you know, what questions should they be asking? What things should they be looking for, either positive or negative to help them think through them? Well, I think you've had an opportunity to interact with brilliant scientists all along and for me it's the brilliant scientist it's brilliant clinicians it's just brilliant people so what are the essence of those people that's how I would think about it. And mentorship matters, obviously brain power matters, motivation matters. So, you know, why is it that some PhD students are not successful? Sure, you can attribute some of it to mentorship, but I really think that it has to do with

motivation and drive, and that's such a critical part of it. So then you'd say, well, why is somebody not motivated? Why aren't they driven? I mean, I guess some people are biologically built that way. But I also think maybe, you know, if you wanted to be nicer about it, you could say, well, maybe they just haven't found what they're passionate about. Because I think that drive passion, they're very stupid, and they come from the same part of your heart or your brain. And so I think part of that is just that. You know, they found the right area. Now there are still having said that there are people that are just super passionate about

something and they want to do it and they just can't, you know, maybe they just need to kind of move along. But I think that in my experience in grad school is that there are usually you can, it's not that hard to identify grad students that aren't successful. It's pretty easy to find out, well, they're missing a major one of those components. So you head back to University of Chicago. You wrap up your last two years of medical school at which point you have to decide what you want to be when you grow up and you pick your ology.

Yeah, so I went to University of Chicago undergrad. So I spent 11 years at University of Chicago. And the first four years were the toughest years of my life, for sure. The undergrad. I learned only one skill set, and that was how to use my brain, how to think, how to think critically. You know, that's why we became,

I think friends instantly at Hopkins was that I feel like that's how your brain is built too. And you've exemplified that throughout your whole career. So for me, I learned how to think, I decided I wanted to pursue biology at a deep level, and I wanted to pursue human biology. So then I went to medical school. Now for me, I think one of the key components of having an effective research career to date, I guess, would be that I had a clear understanding of this idea of translation. So you can do science for science sake, but to me to make really big impacts, you have to be able to translate that to the human condition. So I did three years of

medical school before I left. So I went away after my third year and then I came back. So you already had a year of clinical medicine under your belt. Yeah. So that's also very unusual. It's definitely different, but I encourage all students who are MD PhDs to do a clinical time before they do their PhD. So that might be the nugget of the podcast right there because I don't think I knew a single MSTP student who didn't go straight into their

PhD after the preclinical phase. Right. So for me, it was just so impactful to be, I guess if you say in hindsight, what was the distinguishing factor of the Varmus lab crew? They're all MD PhDs. They had all done clinical. So they knew, really key nuances that were important questions I asked. And it doesn't, you don't have to be an Mb to get that

You know one of my good friends is this PhD who developed a genomics company that we may talk about later And he's a straight PhD. He should know prostate cancer like he does But he really gets the nuances of it. So I did three years of my med school. I went to the NIH I did three years of my med school. I went to the NIH. I did pure science. I met in, think about humans at all, thought about mice and signaling in mice and T cells and mice and so forth. But in the back of my brain, I was always like,

okay, how are we going to change? How are we going to think about the human condition, human disease, breakdown, rebuilding, all that. So from my perspective, I had a jump on, the other straight PhDs in the group because I had an idea. Now, why did I choose urology? Well, this goes back to just an early childhood imprinting.

So there's a couple facts. Number one, my dad is an incredibly famous urologist. My father was the chair of the Department of Urology at Northwestern for 25 years before I took over the job. And he's an incredibly successful scientist. Doesn't do cancer biology. And I didn't really even know he was a urologist as a kid. I just knew him as my dad.

But one of the back stories was that when I was in seventh grade, eighth grade, and beginning high school, we used to go visit my dad's parents, and they lived in Northern Indiana, which is about an hour and 20 minute drive from where we were. And over that time, my grandfather got sick, and I have these just vivid memories of seeing him and their really snapshots in my brain, I recall weekly,

of just becoming sicker, becoming more frail, becoming bed bound, and then dying. And I never really asked what he died of and I don't think I could have processed it what it would have meant anyway if I had asked. But when I was in medical school and I was doing my PhD, I asked my parents what he died of. And he died of prostate cancer. So I was at the NIH, I was doing science, I had done some clinical work, I realized what people in DC, not in science, but in politics were interested in, they're interested in

cancer biology, and they're interested in prostate cancer. So I saw what other people were interested in. And I had this very vivid memories of my grandfather having prostate cancer and dying from it, and I decided that that's what I wanted to do. So when I came back to medical school, I knew already that I wanted to be a prostate cancer biologist and understand the disease.

I also knew that I wanted to be a prostate cancer biologist and understand the disease. I also knew that I wanted to be a surgeon and so I didn't want to be a medical oncologist, although that appealed to me a lot. And I'm always flatter when people think I'm a medical oncologist because those guys were smart. But I knew I wanted to do something. I love working with my hands. So for me, the idea of being a surgeon scientist was just, it just made sense. I love the biology. I love, but I still love the idea of not just conceptually deconstructing something and putting it back together, but actually physically deconstructing something and putting it back together.

So it was a perfect fit for what I wanted to do. For the listener to put some things in context, at the time that you and I began our residencies, I don't really think there was any debate about what the best urology program was in the United States. I think there was a good race for number two, there were lots of programs that would have competed to be the second best urology program in the country, but Johns Hopkins was hands down in a league of its own. And they only take two residents per year. So if there are 400 or 500 medical students graduating who want to go into urology, only two of them get to go to Hopkins. And you were one of them,

which perhaps isn't surprising. Did you want to go to Hopkins for reasons other than it was the best program? Was there something about the environment there that drew you to it? Yeah, it was the people. It's an amazing place that I think about Think about it all the time. So I interviewed there and The chair of the department of time was is the godfather of my field. He made all the Contemporary modern discoveries and prostate cancer and it was real simple. He looked me in the eyes and he said I Looked at your CV. I know what you have the ability to do and I want to help you get there.

So Pat, we all selected you and as much as you selected Hopkins. I guess you could say that, yeah. It was a perfect fit because as we've talked about mentorship is just so much of everything. It's everything in life really. If you're motivated and you have drive,

even if you're not motivated and you don't have drive, you need a good mentor. So for me, I showed up for the interviews. I'd interviewed all over the country. There was places I could have gone that I could have made a good opportunity, a good experience for me to be trained. But when I showed up at Hopkins,

I was like, okay, this is, I gotta go here. So, I think it was a good fit. He was interested in having me train with him and I was interested in training with him. So it was pretty. Did he know your father? He must have. I mean, they're both chairman.

Yeah, it's an interesting story. He, I met him at a, I met him at a, a function in, in the fall before I started. So before I had interviewed and he was, I was at a function with my father. And so my father introduced me to him. And he said, well, you know, what, and what do you want to go into when you finish your medical school?

And I said, well, I'm actually interested in yourology. He said, really? And he said, well, where are you applying? And I said, well, I've applied to all the great programs. So he said, well, did you apply to Hopkins? And I said, I sure did. And he said, that's wonderful. And then I find out from my father that he grabbed my dad

when I had walked away. And he said, I just learned that Ted applied To our program did we give him an interview? And so I made me feel good that you know I had gotten this interview at the best place in the country without using my father's Co-tails to kind of get the job and then I showed up and it was just an amazing. I mean Hopkins was an amazing place I know I know you have many fun memories of the place and I'll never forget just the pursuit of excellence is something I think about all the time.

And that was really the epitome of Hopkins for me. It was the pursuit of excellence among everybody there to be honest with you. Even the chairs of the departments, they pursued excellence. But it trickled down, you know, it trickled down to the everyday employees, the physical plant people, the people who cleaned the floor. They had a pursuit and a passion for excellence. At the time that we are there was amazing. I remember also being so struck by that when I arrived, because of course we're each thinking about it through the lens of what we're going to do. You're going there because of course we're each thinking about it through the lens of what

we're going to do. You're going there because of urology, I'm going there because of general surgery, the neurosurgery guys were going there, but we all had this common first year. I don't remember how many, there must have been 28 of us doing internships in general surgery. Six of us would go on to do that track. Two of you would go on to do. Eurology, there might have been three guys in ENT and Ortho and neurosurgery, etc. But within about a week, I was like, oh my God, this is like the All-Star game. These three guys, and I still remember everybody's names, those three guys that were our classmates who went on to be neurosurgeons were out of control. They were so good.

The Ortho guys, ortho guys get a reputation of being kind of the jokers. These guys were fantastic. Yeah, you know, they were, everyone is just so exceptional. So yeah, you're right. It's, you pay a little bit of price. You got to go to Baltimore.

Yeah, it's all the way to Spain. That's right. Although we both met our spouses there. So, and I had my kids there. So there are some upsides to it, but the reality is that, you know, it's funny because Pat Wallace, my mentor there always would talk about that He would always say well, it's negative selection

People come here because they want to pursue excellence. They don't come here because there's a good night life It don't come here because of x-wires. They come here for that single reason and that's that's a great point I never really thought about that way, but it's so obvious because I remember That's a great point. I never really thought of it that way, but it's so obvious because I remember being so sad about having to leave California to train there, but at the same time realizing. And talking a lot about it with Steve Rosenberg, who had done his MD and PhD at Hopkins, that you only get one opportunity to train at this. This is the phase of your life to do this.

So go to the best place you can go that fits with how much you want to work. Let's talk for a moment about Pat's work because I don't think it can be overstated and I don't think, I mean, in many ways, I think Pat Walsh was a very unique mentor to you specifically, but in many ways, the field of yourology today is different because of him. And I don't think, and I've thought about this, knowing that we were going to talk today. I've spent the last couple of weeks thinking about this. And I have a hard time coming up with people in the modern era that rival him. John Cameron potentially being one with respect to pancreatic surgery. But

I can't think of someone in the last 30 years that has so fundamentally changed the course of one operation, its impact on one disease as Pat. Now am I missing an obvious example? Well, within urology I think I can't think of anybody within urology. And the other point is I'm sure that there are brilliant outstanding people that have changed an operation in a way that alters the course of those individual patients. But one of the things I think about a lot is that walls would always tell me, you know,

you can't make important discoveries unless you work on important problems. So prostate cancer is an important problem and it's an incredibly prevalent problem. So yeah, there's probably some guy out there who came up with the best way to do a Nicknack whatever surgery, but if it doesn't have a high impact, it's probably not noticed. So yeah, I think that what he did in our field was, you know, really was never been done before

and probably won't be done again. And he did it for a problem that was incredibly important. So let's talk about the state of prostate cancer surgery for men prior to Pat's work. If a man had prostate cancer, what would be back in the early 70s, even late 70s, right? What were the treatment options for him? Well, at the time that Walsh was training, very few people with prostate cancer had surgery. That was because it was a potentially life-threatening operation. People would die from extreme blood loss. People were incontinent.

People were for sure impotent. Let's stop there for a second because this is one of those things that I think if unless you've been in an operating room it's hard to understand why the blood loss from prostate cancer surgery could be so deadly. It's the same reason until you see a trauma where somebody is shot through the pelvis. You can't understand how did that person die? People get shot in the chest and they walk away sometimes if it's not through the heart or a pulmonary artery or vein.

And yet, a cross-pelvis gunshot wound is often quite fatal. What is it about that anatomy that makes it so deadly? It's the large number and variable distribution of veins in the pelvis in general. And why is it the veins, not the arteries, Terry? I love that. I love that I get to do this with you. I mean, you know, the vein is just,

the wall of a vein is as thick as a piece of paper. So it's prone to tear and it's hard to repair it if you do tear it. And an artery is much thicker. It has much more resiliency to it. And it has to do with the amount of flow going through both of them and pressure. So yeah, there's a lot of veins in the prostate. In the pelvis, there's a lot of veins around the prostate. And the distribution, the exact location is incredibly variable. So

they're more like venous plexuses versus an actual vein that you can name. But if you get into the inferior vein of cave, a man, you're in trouble too. There's no doubt about that. That's happened to me a couple of times. So point is that anytime you, you know, an artery is the real deal, but it's just easier to control it. And oftentimes if you cut an artery, it'll go into spasm and it won't even, it'll just stop bleeding on its own. And that's not true for veins. So for one, and then also there's the depth, right?

There's the actual exposure is really tough in the pelvis. It's one thing to look at the kidney, where even though it's in the retroperitonium, you can be staring at straight in the face without too much work. That's not really the case in the prostate. Yeah, so, I mean, the way that Dr. Walls describes it is that, you know, people had done anatomic studies

for many, many years, right? I mean, for decades before surgery for the prostate kind of was attempted to be performed. But the anatomy, when you fix a body and you study it, it really compresses a lot of these sinuses, and so you don't really fully appreciate where they are and what's happening and so forth. Anatomically, an artery is preserved, but these kind of venous plexuses were not. So the anatomy of the pelvis was not appreciated, but I

will say that in 1904 at Johns Hopkins, the first radical prostatectomy for cancer was performed by the chair there at the time. And he did it through a perineal approach, which is the space between your scrotum and your anus, basically. And when you do the surgery that way, you avoid, and the reason is that's the closest place that the prostate gland is to the outside world. That's right.

And if you do it that way, you avoid a lot of the veins that bleed just, you know, catastrophically when you approach the prostate from kind of above versus from below. And so that operation had been, was being performed and it was considered to be, you know, was definitely safe. I mean, this life-threatening blood loss did not occur. And the problem was it wasn't a very good cancer operation. Why is that? Well, it had to do with exposure. Number one, I mean, you're doing, you know,

the prostate is very deep in the pelvis. So for the lay people, the way I explain will, whereas the prostate, I explain to people that the pelvis is like a ring of bone. And off the ring, hang a bunch of muscles and those muscles form a hammock. At the bottom of the hammock is the prostate. So it penetrates through the muscles and then that's where the urethra, the tube that

you urinate through comes through the pelvic floor muscles and then goes out of the body. So it's deep in the pelvis, it's hard to access. It's hard to access from the perineum and it's hard to see what you're doing. And it's harder to kind of excise tissue widely in that area. The exposure is tough when you do it from above, but it's hard to see what you're doing, and it's harder to kind of excise tissue widely in that area. The exposure's tough when you do it from above, but it's even tougher from below. So, the life threatening bleeding wasn't there, but part of the reason that the bleeding didn't occur

when you did a perineal approach was because they were leaving part of the prostate kind of in place. They were staying away from the area where the big veins were. And so, when you do that, it would be safer for the patient, but less oncologically sound. So, and I can't believe I'm blanking on the forefathers. Obviously, Halsted, Osler, Kelly, who was the, and Kelly was the gynecologist. Obviously, Osler, the internist, Halsted, the surgeon. What was the name of the urologist? The first urologist at Hopkins was one of Halsted's trainees that was Hugh Hampton

Young. So Hugh Hampton Young was a Halsted trainee, and so people probably don't realize, but many sub-specialties of medicine came out of the Halstedian era at Hopkins. And so orthopedics, radiology, urology, these were all sub-specialties that basically were Halsted telling Hugh Hampton Young, I think we should start an institute or program for people with your logic problems. Now Kelly was doing some of that also at Hopkins, just more on the female side, but that concept came out of Hallstedt really assigning Hugh Hampton Young to do that. And the story is that he literally bumped into him in the hallway and told him,

you're going to go work on this. He didn't really want to do it because at the time it wasn't very sexy, but he did and from there he really began the whole specialty of Eurology. Yeah, that's sort of the other thing about Hopkins that never got old actually was to walk through Blalock and look at the photos of all of these old photos of people who literally created the field of surgery. The lineage there was sort of staggering. Yeah. I think one of the things that you I certainly didn't appreciate was to really take it all

in at the time. I mean, I had the pleasure of being hard to when you're sleeping, I think, an average of 28 hours a week or whatever we slept. Right. exactly. But the idea of what we did was pretty amazing. I mean, remember, we had Sunday school, right? Yeah. Oh, I loved Sunday school.

You know, we would show up. And can you explain to the listener what Sunday school is? You and I might have been two of the, there weren't many people that probably loved Sunday school, but you and I had scored it. So when we were interns at Hopkins, there was no work hour limit. And you know, the expectation when you got there was that you'd work seven days a week You would work eight days a week if there eight days in the week and so Sundays was a day that you'd go in and you'd sit with the chair of the department one of the most famous

surgeons of all time really and he would lead the discussion on A topic for the day it often started with history, right? We would do history of surgery history of surgery at Hopkins. And those are some of my most favorite kind of discussions was him just talking for 45 minutes about somebody. And then we would present cases. And then we would talk, we would practice our suturing. I remember we, I remember I think Julian Sosa, who's the's the Jared UCSF now was taught me how to tie a square knot

You know what I mean? So and also once a year we each took a turn presenting something back to the group I still remember what I presented on I presented on the Warren Shunt really there's an operation that I never got to see because even by the time We were residents, interventional radiology had completely nullified the need for that operation. But as a medical student, I became obsessed with the history of that operation, because of how dangerous it wasn't how complicated it was.

This was an operation for the folks who maybe don't spend a lot of time on the at-worn shunt Twitter handle. I just find no such thing. Hope someone creates one after this. It's an operation that was done for people with elevated pressures in the liver, and this is something that happens when people get cirrhosis. So this was basically an operation that would alleviate that

by creating a shunt in the liver. But I still remember that, and I remember typing it up, and this was back in the day when I would cut pictures out of textbooks and tape them on, make photocopies and it was awesome This was old school. Yeah, so that was eight to ten every Sunday morning, right? Yeah, and so Those kind of things I wish I could just you know people say I wish I could go back to high school. I wish I could go back to college in many ways I mean I do internship all over again. I would I mean we we were there at what a hundred and thirty two hundred and thirty six hours a week, but man, I would do it all over again. It was awesome.

We did have amazing times. And I feel fortunate. I mean, there was just a great group of people we met. You and I met immediately on day one and then work together. We were together September, September of our intern year. We did pediatric surgery together. And Karen Kling was our fellow. She is now an attending in San Diego. I bumped into her in the grocery store like a year ago. She was great. She was incredible.

Yeah, she was awesome. John Vogel was our senior resident. She taught me how to put an NG tube in that served me an asogatric tube for the listener is a tube that you sometimes have to put in a patient's nose down behind the fairings and then into the esophagus and into the stomach. This is something that is so ubiquitous in surgical care, but so wildly uncomfortable for a patient because the patient is usually wide awake when you're doing this. And I remember one day, Vogel, I remember where we were. It was just at the ground level of CMC.

He sat us down there in the playground and said, look, you two knuckleheads. You have got to learn how to put an NG tube in without killing somebody. And he didn't mean literally killing, but he just meant tormenting. And do you remember the Vogel technique? I do still, I remember him telling me. It was like, because everybody thinks

that you're supposed to put the NG tube up the nose. Yes. And he's like, it's straight back. That's exactly right. And so he's like, you get the cup of ice, you get the ice water cup, you put the NG tube up the nose. It's straight back. That's exactly right. You get the cup of ice, you get the ice water cup, you put the NG tube in, you put a wicked bend on it, you put the lidocaine jelly in and that's exactly the key point. Do not go up, go directly back and you curl down and then you give them a little straw and

you tell them exactly once you hit the back of the orafairings, take two big sips. And this was a game changer, Ted. It was. For the rest of my residency, I was throwing in G-Tubes, and if you looked at me, you got an NG-Tub, and it didn't hurt. The thing that the listener will not appreciate is the layer of comedy associated with this, because this was done in what you described as the first floor of the pediatric hospital, which was called the zoo, right? Yeah. And so this is

this is a brilliant surgeon, John Vogel. He's the head of colorectal surgery in Colorado, teaching Peter Tia, brilliant surgeon, Ted Schaefer, just getting by in front of life-sized stuffed animals of like giraffes and lions. It was hysterical, right? It was just comedy. Yeah. That entire... That might have been certainly the best month of my internship.

Yeah. It was fun in terms of having great, many great months. Yeah. Pure jokes. So let's go back to Pat. I got us a little off topic. I actually got us way off topic because we were talking about the bleeding. But there was this other enormous complication of a prostatectomy, which was it virtually guaranteed that a man would not be

Continent with respect to urine and would not be able to regain erectile function. And so I'm guessing that many men When faced with an operation that's going to leave them in a diaper unable to have an erection might opt for not having surgery. Yeah, so people had radiation. Radiation has changed a lot too, so it was bad radiation or bad surgery effectively. But when you can actually see what you're doing, just for the listener, doing something when it's pitch black out versus daylight makes all the difference in the world. So you would go into the operating room with him and he had just had a mastery and he could control,

he understood where the veins were, he controlled them by suturing them before they started bleeding. And by doing that, you could actually see everything. And once you could see everything, it was obvious. You'd be like, hello, why aren't people doing this for that? Now, the ability to maintain potency and preserve sexual function was something that it's not so obvious

how to do that, but he figured that out by working with some anatomists and really just studying and talking to his patients and listening to what they had to say, he also recorded all of his cases, which I do now too, and I studied them. And he learned how to kind of... I didn't know that about Pat. He would record all the operations and study them.

And I didn't realize that you were doing that either. I do now. It's much easier now for us. We just hit the button, but every single case I recorded. And we're working on, when I'm working on with one of my residents, just making a photo video library. So what was hard for him, and he's published, and he put out on DVD, you know, his operation, you can see it on YouTube, and it's a brilliant thing.

But one of the things that makes doing any surgery fun is that there's so much variability in anatomy. So what I'm working on now is a video library. So 10, bladder necks, 15 of these, because there's so much variability in how the tissues present themselves to you, and then how do you handle that? And that's part of what, you know, surgical skill and hours in the cockpit do for you. So, we're doing with one of our lab residents issue.

We're just taking all these videos. And so, whenever I do a case, and the anatomy was really nice for X, Y, or Z, we'll tell them, they have pull that case. And it's in the third 20 minute clip and pull it and make a short, you know, just make a clip of that for particular steps of the procedure. Was there a moment when Pat realized he was on to something and that this was, you were, we were basically witnessing a paradigm shift, which is such an overused term, except here it's not at all,

it's actually an understatement here, but such a paradigm shift in how an operation was gonna be done. I mean, this would have been in the early 80s, I'm guessing it was fun. Yeah, well, mid to late 80s, our late 80s early 90s. And so it was, I think he knew all along

he was on to something and he was very confident. You know, he's not a shy guy and he'll tell you that. So he was incredibly confident that he was on to something and that what he was doing was the right thing to do and was very convinced of that and was convincing of that when he spoke about it publicly. I think that the general community was less convinced that that was what he had done was really happening, but I mean, I saw it, you know you know I mean I was really training there at the heyday the peak of Brady Eurology, Johns Hopkins Eurology, and so I got to see it in real life and you know I never saw bad surgery. That's the thing. I mean, you know

We trained at this place and you didn't really really did you see people do bad operations? So part of learning is to see the good stuff and the bad stuff and put it on the perspective and we didn't have most of the time That didn't happen there. So I saw it and I think he was convinced of it from the get go. So you're saying it just kind of took a little bit of time for the day to speak for itself. I mean, it results. So so if a patient today goes to a highly trained or competent urologist and is going to have a a prostatectomy and this it's a 60-year-old man.

What can you guesstimate about his probability of regaining sexual function? It's not 100%. And it's not 100% because it used to be zero, but now it's... Well, the nerves that we preserve at the time of surgery to optimize recovery of sexual function are not myelinated, so they're incredibly sensitive to any kind of manipulation, any kind of trauma. So one of my good friends is a hand surgeon and he does micro vascular nerve grafts all the time. And the nerves regenerate and regain function.

They do that because they're myelinated. They're incredibly protected. I didn't realize there were such thing as non-myelinated nerves. Are there other places in the body where these exist besides the prostate? I'm sure there are. I'm below the belt guy. I don't know. Is there an evolutionary reason that those would not be myelinated? I don't know, but we can, I'll call Pat Walsh up when we finish this and he'll tell me for 20 minutes what it is I am and how I didn't know that. Can we record that discussion? We can. Okay, so that's a very interesting point that I actually was unaware of, and I can see

now why that makes it that much more difficult. Right, because you can preserve this tissue and you can do it in a way that's minimally traumatic for the tissue, yet it's not a guarantee that there'll be a 100% recovery of function or any function recovery, right? And so that is the variable, and that's the fact that it still hasn't changed. You know, like Dr. Walsh would always tell me if we could do the perfect operation, there would be no dispute about doing prostate cancer surgery, perfect operation, 100% cancer control, and no side effects.

So I think in this day and age, you can be nearly perfect for kind of urinary control. You're never going to be perfect. So when people say that none of their patients have urinary leakage, it doesn't make any sense, because if you actually survey 60 or 165-year-old guys, 4% of them will have urinary leakage. I mean, so incontinence is something that happens. It's much more common in women, particularly aging women, but it also occurs in aging men. So to say, well, I do 100% of my cases,

and there's no urinary incontinence. That's kind of, it's better than the baseline, so it's hard to believe. Yeah, but you can get people up to very, very close to that number. So I always tell people, for me, personally, 98% of my patients are totally dry, where one small pattern line or day, which often people just wear for protection when they're out and about, functionally totally fine. Now, for a 50 year old man, I think there's a over 90% chance that you can recover sexual functioning.

Yeah. But with each deck member, you know erectile dysfunction is a disease of the aging male So for each decade that somebody gets older there's a decline in sexual function So even if people say that they're totally potent and they're 70 They'll tell you if you ask them. No, my yeah, I'm not as good as I was when I was 20 So there's that component of things and the other factor is cancer. And it's not like there's the prostate. There's five millimeters of tissue. And then there's this nerve bundle. There's the prostate. There's no capsule or lining in casing the prostate. And then there's the nerve-assular bundle of walls, named after Dr. Walsh. So you have prostate. The prostate itself has different zones or different regions.

Prostate cancers develop in the peripheral region or peripheral zone. So right at the edge of the prostate. So you have a tumor at the edge of the prostate and then you have the nerve bundle. And so you're talking about one or two cylinders. That's kind of a cruel trick of fate is to have the cancer is not developed centrally. They don't develop centrally, they develop peripherally. So I understand why patients by listeners just say, why don't you just, you know, why don't get it? Because in many cases today, I've published on this a lot. Now, you know, there's prostate cancers that we pick up today are just bulkier, they're

more aggressive. And so when you have a tumor that you know is going to be outside the prostate, you know it's extra prosthetic, it's involving the nerve bundle a lot of the times. And so you have to remove part of it, you have to remove the tissue around it to try to clear your margins. And so when you do that in a 65 year old guy and you take out half of his nerve on one side, it's unlikely that he'll be able to regain sexual function on his own.

Now these days, I try to be very upfront about that and I try to set appropriate expectations. We have special tools that we have in neurology that will enable a man to get total satisfaction sexually. We can maneuver around that, so to speak. These days, many of the people I see have very aggressive cancers that are, quote, unquote, the real deal. So you really have to be careful

on our number one goal for doing cancer surgeries to get the tumor out. Let's talk a little bit about prostate cancer because it's not a cancer that comes without its controversy. So let's start with the biggest kind of risk, or certainly one of the biggest controversies, or things that would confuse the lay person because about every year the advice changes on this thing called PSA.

So what is the prostate specific antigen? PSA is a protein, it's made by the prostate, and its normal function is to liquefy semen. So it's highly expressed in the process. So the way I explained the process to people, it's the best analogy I can come up with is if you think about it like a sewer system, you have the main sewer leaving the city. That's the urethra. That's the tube that we normally urinate through. But this channel also delivers semen out the tip of the penis. Off this main sewer are slightly smaller sewers that go to different neighborhoods.

Within the neighborhood, there's a sewer that comes out of the individual house. And the individual houses in this analogy are prostate epithelial cells. They make components of the semen. And the semen is used to give nutrients to the sperm while it's trying to fertilize an egg, to enable the sperm to penetrate the cervical mucus,

these different functions. PSA is a protein that breaks down the semen and liquefies it, and people think it's important for this whole process of fertilizing an egg. So that's what it does. And if you look in the semen, the PSA numbers are 100 million per ml. I mean the numbers the amount of this protein in the semen is astronomically high.

So That's what it is. That's what it does. So how do we use it as a tool to screen for prostate cancer? Well, we check the values of the PSA in the blood. So since the prostate is a sexual gland, if you check the values of a PSA in a eight-year-old boy, it would be zero. Because there's no testosterone in that boy, there's no sexual development in that boy, and therefore there's, you know, I mean, there's some, but effectively no. Before puberty, there's very little levels of testosterone, there's no effectively prostate epithelium, and there's no PSA.

As a boy goes through puberty to become a young man, and then as he goes through the aging process, his prostate develops. And then it starts to produce PSA as part of the components of the semen. Now, there is a certain amount of leakage of the PSA fluid into the bloodstream. It's not, quote unquote, supposed to leak into the bloodstream, but it can. And as the prostate gets bigger, so think about this concept of this underground sewer system,

the New York City sewers, right? They're getting older, they're getting leakier. And the bigger the prostate gets, and the prostate gets larger as we get older Some of these pipes get leaky and some of the PSA leaks into the blood So it was discovered in the 80s that there's this prostate specific protein that you can pick up in the semen and you can also see in the blood and So it is not cancer specific, it's prostate specific. And it's actually a very good biomarker for prostate size. The bigger the prostate, the more leaky it is, so to speak.

And the leaky here is the higher the numbers can go in the bloodstream. So there's two variables that can progress over time. The size itself, which you could talk about that independent of size. So, two 30 year olds, one guy's got a five gram prostate, the other guy's got a hundred gram prostate just to make it a stream. You should see a difference.

But also, two guys with the same size prostate that are two decades apart, you might see a higher PSA in the older. That's right. So, and if you do, for example, like we were always taught, you know, in, you know, residency, even though I wasn't a urologist, you still once in a while have to, you know, we still do urology rotation. If I recall, you wouldn't check a PSA on a man right after doing a rectal exam on him,

because in theory that could artificially have raised the PSA, presumably by creating more of an insult and increasing that flow,ushing some of it into the blood, the bloodstream. So what can make the PSA rise besides just having, getting older and having a larger prostate? Well, if you get an infection in your prostate, so think about that like you got your city, you have your sewer network and there's an earthquake. All of the pipes are rattled a little bit

and they all are extra leaky. And that's what an infection is. It's not infections in the prostate are either all or none really. They're not vocal. So, the whole prostate gets more leaky and the PSA number can go way up. The other way to think about it is if you have a cancer and the analogy would be low, there's a city block that has the pipes, you know, the sewer systems clogged. There's more backflow into the bloodstream, and that's

how it pick it up. That's not really how it happens, but that's a good way for patients to think about it. So, what is a normal PSA? Well, a normal PSA is age-adjusted. So, a normal PSA for a 40-year-old is around 0.5 to 0.6 nanograms per ml. For a 50-year-old, normal meaning this is the median for all the population. For a 50-year-old, normal meaning this is the median for all the population. For a 50-year-old, it's one, and so it kind of goes up stepwise by decade. So there are age adjustments that we do for the PSA number. Now, what are PSA numbers that tell you you don't have a cancer? There's no PSA number that is 100 percent no cancer. But there is a proportional rise in cancer detection with rising PSA numbers. So originally the cutoff was set up a PSA of four. We do, you

know, we think about things more based on the individual scenario. So if you're a younger person, if your PSA is more than 2.5, that's usually considered to be abnormal and may want, you may need further workup. You don't need a biopsy right away these days, in my opinion, but you need further workup. So it depends on the age of the patient, and depends on how also their prostate size. Now, how many guys will go, and when they get their PSA checked, there's another thing that gets checked, called the free PSA, and then a number is reported, which is the percentage

free, which is obviously that, you know, if their PSA is three and their free PSA, and then a number is reported, which is the percentage free, which is obviously that, you know, if their PSA is three and their free PSA is one, then the percent free is reported is 33%. What does that mean? These are different ways for urologists to try to fine tune this prostate-specific antigen test to make it more a cancer-specific test. So again, PSA just goes up when you have, and every man has, it's not cancer specific. So a percent free PSA was the first way that urologists began to look at, well, what's the chance that a PSA of four is coming from a cancer versus a PSA of four coming from just benign overgrowth. So remember, there's a lot of factors in play. One would be if you had a man whose prostate volume was 80 grams,

that's big, and his PSA was 4, well, that's a low ratio. That's something called PSA density, how much PSA is made per gram of tissue. So you'd say, well, that guy, it's very low chance that he has a cancer. That guy would also have a high percent-free PSA. So percent-free PSA is another way to just look at, well, how much of the PSA's produced from benign cells versus cancer cells? So if two guys have a PSA of four and one has a free of one. So he's 25% free and the other guy has a free of three,

which is 75% free. What's the different physiologically in those situations? Well, there's less bound PSA in the lower percent free and that's more often associated with prostate cancer. So that's just a correlation. So it's not like it means that in other words, you can't infer what, because I would have assumed that the binding protein is in the periphery It's in the plasma, right? Yeah, it's it's bound up when it comes out of the epithelial cell

So it's just how it's processed. So PSA's process is not a full-length protein when it's born in and so the other way that we now So just for the listener. so we have absolute cutoffs for PSA for an older man, 2.5 and younger man, but they're all really case specific in my opinion. Percent free PSA was the first way to say, let's try to fine tune what the PSA means. So a high percent free PSA is associated with a big prostate, less of a chance of prostate cancer.

A low percent free PSA is associated with a big prostate, less of a chance of prostate cancer. A low percent fee PSA is associated with a higher likelihood that that PSA is produced from a gland with prostate cancer in it. The other variables that we use are PSA density. So that's highly predictive of what's going on in the prostate. So a easy threshold or cutoff for you, Peter, we talk on the phone about some of your patients. Percent free PSA density, more than 0.1. It raises a little bit of a red flag, a PSA density of more than 0.15. That raises a red flag. So, think about it. And a median prostate volume for a 60-year-old guys 40 grams. So 40 gram prostate, PSA less than four.

It's probably, it's pretty safe. A PSA of six, six that raises red flags and you know the sum of your own patients that, okay, that guy probably has something going on. So that's how I think about it. Now think about the 80 gram prostate with a PSA of four. You have these patients in your practice. They don't have cancer on average, right? A percent free PSA helps with that.

There are two other new tests that... Yeah, so you got me onto the 4K two years ago, and I really consider it a game changer for the guys like me who were in the peanut gallery. So I don't... I make it my job to know as much as is knowable with the time that I have about every possible disease that could have flicked my patients. But that means I need to spend as much time

thinking about colon cancer as I do coronary artery disease, as I do prostate cancer. So for me, the 4K, which again, you didn't, I mean, you did me a great service. Not only did you get me interested in, but you introduced me to Andrew at Memorial Slown Kettering. I'm blank on Andrew's last.

Andrew Vickers. Yeah. Amazing guy. I mean, the guy couldn't have been more generous with this time. I mean, just gave me the schooling change of the Borneo on this topic. So good. You know, we put together a patient hand out on this thing and he even edited it for us. I feel like not, I'm worried not enough patients understand that and I'm worried not enough

primary care physicians understand the importance of the 4K test. Can you explain how that has changed the way we do things? So this test you're alluding to and there's another test that performs equally well called the prostate health index or PHI test. These both leverage off this idea that prostate cancer cells make PSA differently than benign prostate cells. And so the 4K score is the 4k chalichrine test. It takes PSA, percent free PSA, intact PSA, and HK2. It takes those four prostate specific proteins produced. And it has a calculator

to really just discriminate between a cancerous cell and a benign cell. PHA uses the similar concept. It uses something called minus 2 pro PHA, which is PHA for all the scientists out there, plus two amino acids on the 5 prime side of it. So minus two pro PSA, right? And you measure those specific PSA-based proteins in the blood. And the 4K score is great because Andrew Vickers and Hans Lea developed it with this other great urologist, Peter Skardino Memorial. And what they looked at was, well, what's the chance that this person is diagnosed with

and has high grade aggressive lethal prostate cancer, and it gives you a percentile chance. So when you get the 4K report, it's actually a really nice report. It'll say 2% chance, 20% chance, and so forth. And so now, as you start using this in your practice, they now also give you the PSA. So you can see the PSA, and you can say, wait a second, this guy's PSA 6, but his 4K score is 2, it's safe. What I really like about it is, and so when we do our, usually with our patients in their second year,

sometimes in the first year, but usually in their second year, we do a cancer screening program where we kind of walk them through every single cancer that you could possibly die of, and then we go cancer by cancer, risk by risk, and it's a very lengthy process on the back end. For the patient, we simplified it, takes about 90 minutes to go through it. But for the males, when we come to this, I always view this as one of the better, I said I wish every cancer had a test like this because as we'll come back to, you know, pretty much

every guy is going to die with prostate cancer. cancer had a test like this because as we'll come back to, you know, pretty much every guy is going to die with prostate cancer, but fortunately most men will not die from prostate cancer. But the job is to figure out when a guy has prostate cancer, is you alluded to earlier? Is this the bad one? Or is this the one that if you muck around with it too much? And so what I guess Vickers and his team have been able to do is figure out that there's now enough data that you can basically turn this into a binary test, you know, which, so PSA would be a continuous variable, right? And when you want to test the sensitivity and specificity of a continuous variable, you

have to use something called a receiver operating characteristic curve, and it becomes quite complicated because the question becomes what cut off? And as you alluded to, it's very difficult with PSA because it has to be age and volume adjusted. So now it's a three-dimensional receiver operating characteristic curve where you would have a different AUC area under the curve for each point in time and volume. I mean, that becomes almost inconceivable.

And yet, the 4K has basically allowed us to say the following. If your 4K score is less than 7.5%, and I might butcher the numbers a little bit. That's right, number 8. But if it's less than 0.5%, the probability that you will be alive, the probability that you will die of metastatic prostate cancer is 1.6% in the next 20 years. Yeah, almost the lifetime of the patient. And that's based on this data from Andrew's partner, a code developer, Hans Lillia, where they had this incredible

serenade base from Malmo, Sweden. So they could track it. And then the reverse is, if you're greater than 7.5%, I think it's like 16 or 17% chance in 20 years. That's the binary cutoff is 7.5%. But it's a continuous variable. But above that, it's continuous. It's not like if you're above that, you know,

it's a 50%. So it varies based on the number. So where are we today? Let's take a journey backwards in time. In the late 1980s, 40% of men who were coming in with prostate cancer had metastatic at the time of presentation. Just like a lot of cancers, other cancers that we diagnosed today. And that was how it was then. There was an epidemic of deaths from prostate cancer.

We were getting a better hand on how to control cardiovascular deaths. People were coming in with aggressive advanced cancers. Prosthet was one of them. We, Tom Stamey, took this PSA test, and he first made the observation that you could use it to actually follow men after their cancer treatment. And if the number went up, gosh, that meant that their cancer was back. It was just a game changer, right? This is the first time this was ever done.

And then Bill Catalona, who's one of my partners here, one of the other godfathers in the field, he said, why don't we use it to screen people to pick up cancers when they're early and curable, not when they come in and advanced. So the change, what year was that? That would have been a 1992, 1990 FDA approval. So they set up arbitrary cutoffs. This is what this idea of mass

screening took off. And, you know, it's been sold to the public like, well, the urologists were out there just to make money. This is what we are doing and to get rich. No, it wasn't that. It was because at the time the test was developed, it was the first biomarker for cancer. Pick up a cancer early if you pick it up, treat it, and cure that patient. Now, over the 1990s and early 2000s, what we realized is, well, guess what? We're picking up a lot of cancers, we're treating a lot of cancers. Number one, we're increasing and reducing the deaths from prostate cancer. We're reducing the incidence of metastatic prostate cancer at presentation.

It was 40% in basically 1990, 40% of men coming in with prostate cancer metastatic at the time. By 2000, it was 4%. Now, the skeptic is going to say, and this is such a controversial topic, so it's so good that we're doing this, the skeptic will say, well, that's just lead time bias. I mean, all you did was catch a bunch of men earlier, so you have a much bigger funnel, right? Right. So by the way, the same controversy exists on mammography. So, you know, I can't wait to actually sit down with the Ted Schaefer equivalent of breast cancer at some point, because I realized that an episode like this

is probably a little bit more geared towards male listeners, or, you know, probably the female listeners who have males, spouses, or people they care about going through this. But it's interesting to watch the rise of mammography and the rise of PSA go through this parallel thing. And colonoscopy, though, to a slightly lesser extent, but really being the big three mass employed screening tools. Well, it's been written about. Peter, and you've written about this. Well, Peter Albertson is another Hopkins alum.

He's a chair at Connecticut, and he's an anti-screener effectively for prostate cancer. He wrote about this, and he showed that if you just look at incidents of metastatic prostate cancer, incidents of metastatic breast cancer, there's no change with the implementation of mammography. There's a huge drop in the incidents of metastatic prostate cancer with the implementation of ps. So why is he an anti-screener? Well, he just he was historically, he wrote this paper and and show that there is a huge difference. So now with screening, you have increased detection. And what we've learned is unlike, let's say, pancreatic cancer, where most of the time, if you picked it up early,

if you did nothing, you would die. Not everybody who has prostate cancer has a lethal variation of it. And so initially, we developed a biomarker to pick up all prostate cancers. That was the PSA blood test. We picked them up. We treated them. We reduced deaths. We also over treated people, people who had a cancer that would never have been lethal in their lifetime. That's the dying with, you know, not the dying from. And this is something you and I used to talk about nearly 20 years ago.

I remember sitting in the cafeteria because, you know, even though, you know, we were still interns and basically two knuckleheads. you knew you were going to do this, and you were always head and shoulders above everybody else in terms of what you understand. I remember asking you, I was like, I don't get it. Why do some guys get prostate cancer, and it seems to be relatively uninteresting? And another guy is get it, and they're dead in two years, and it's devastating as pancreatic cancer. What is it about the biology of that? It strikes me as more a function of the biology than the environment or the host. But I can be wrong, of course.

But I remember talking about this a lot and really coming away scratching my head thinking, I don't know what clue what's going on with this disease. I mean, I'm still scratching my head about it because that's what my whole research program is all about is what's the molecular biology of lethal prostate cancer? So we'll talk about that in a second, but to circle back to our story. So we diagnosed many men with prostate cancer. We treated men and we saved their lives and reduced deaths from prostate cancer period. It's not debatable. But along the way, there were people that were pulled in and were treated who did not need treatment.

But there's a lot of smart people who have studied the biology of prostate cancer, and we realized that not everybody who was diagnosed with it needed to be treated from it. And so the 4K score and the prostate health index help us identify men who have life-threatening or lethal, potentially lethal prostate cancers. And so those are great screening tools. They're not considered, or the government doesn't like them as first line screening. So you should, they recommend you do a regular PSA blood test. If it's at all abnormal, remember 70% of men have normal PSAs if they're such a thing.

And by the way, what do we have a sense of what percentage of those men can still harbor a lethal prostate cancer? Well, Vickers would know that data and they've published on that. It depends what you say, normal and not normal is. Below, I mean, a PSA, below three, there are still men that have, if you just do one test, it's assuming it's not a lab error or you're missing a lab. No, no, below three, I still think the 4K data says it's somewhere around I want to say 10 or 15%. So it's not a single digit thing.

Another big opposition in the screening world is the quote-unquote unnecessary biopsies. And I say quote-unquote not because I'm diminishing or minimizing that, but the idea is look a prostate biopsy is a transrectal procedure for most men. It's a morbid procedure. It's not comfortable. And just as it's not comfortable for a woman to have a needle put into her breast, and the fear is, hey, we're doing too many of these. I want to circle back to that, but my view on that today is diffusion weighted MRI and you know, just the MRIs that we have today have really cut back on those biopsies, but I

want to get you, that's just my take as a non-eurologist with my patients, but I want to come back to this. Well, also the government said in 2008, first for people over 75, and then in 2012 for all men that you shouldn't do PSA testing. And when the internist got to go ahead and not do it, I mean, it's easy to not do it, right? You just don't do it. So what would you predict would happen if you stopped screening for prostate cancer?

Well, you would predict it would go up and it would depend on the time horizon of the disease. So if you stopped screening for prostate cancer, you'd predict that the detection of prostate cancer will go down, right? You're not looking for it. But you're gonna have a greater number of late presenting diseases show. More lethal disease. So we published and some of my good friends

in urology have published that yes, that in fact has occurred. So if you look at starting in 08 or in 12 when these two big shifts occurred since that time, there's been a rise in the incidents of more advanced prostate cancer. So the cancers that are picked up today, even with this short window where we stop screening aggressively with the internists that there's now more aggressive, more lethal disease.

As of today, I still believe that the formal recommendation for screening for prostate cancer is each physician and patient should discuss together. There is no formal recommendation because when we go through each cancer with our patients, we show them what the ACA, what the American Cancer Society says, the U.S. Task Force on Preventative Services, the NCI, the New England Journal of Medicine did a review on every cancer and there's one other one, one other group, oh, the CDC is the fifth body to weigh in. And we show them, here are the recommendations from all five of these for every cancer.

And I remember when that shift changed to for prostate cancer, there's no more recommendation. Well, the recommendation is talk about it with your doctor, which is a bit of a past the book. Besides the, I think the American Academy of Family Practitioners and they don't recommend PSA screening still. I'm not sure why, but that's a different discussion. But the bottom line is that almost all the guidelines now say it's a shared decision-making process, which I think makes perfect sense. That's how I view modern medicine.

Yeah, it does, in theory makes great sense. What I worry about Ted is there's a bunch of patients that get caught, they don't have doctors like you or me who are willing to be able to have have the luxury of the time And the ability to educate themselves to do that because I still see a lot of patients that show up and They're not getting screened because their doctor's basically saying well, obviously this is quote-unquote controversial You know, I sort of remember hearing that we shouldn't have been screening so we're not gonna do it And that's that's sort of my fear with these things. Well, I think shared decision making, it requires, well, so then, to me, conceptually, it makes a lot of sense.

In reality, what does that actually mean? Well, that's the next question. That's the next unknown, right? Is, well, how's our shared decision making process? How does it occur? And when a patient sees you, that's different than when a patient sees an average internist, let's say, and it's different when a patient doesn't see any doctor. So the idea that there's the bus that rolls up that just does your blood work and sends

it back to you in the mail, that's terrible. I mean, I did that when I was a resident. They paid me 50 bucks to go man the bus and do that. That's not really doing that patient, those individual men, any, you know, any, they're not helping those people because you don't know their whole health history, you know, and all that. So I experienced that and, you know, I got into it with Otis Brawley about screening and, you know, he raised that point and it's valid.

I did that when I was resident because I was told to do it and it wasn't that's a mistake just bringing up the bus and doing blood tests in the Walmart parking lot. That's not a good answer. Having a discussion with the physician is their internist is a good answer because I have many patients. What were the bus parameters by the way? Eight men between eight and a guy who showed up. Literally any dude who shows up to get a free PSA.

Yeah. You know, and then they said, how did I not know you were doing that? I did it once or twice, you know, when I was a lab year resident, and they'd say, go ahead and, you know, do you want to earn 50 bucks? And I remember I drove to some civil war town in Northern Virginia.

It was a cool town, you know, and did it, you know, on a Saturday for half day. And, you know, I did it, you know, and it was like, you know, in hindsight, you say, okay, I get it, you know, it was worth doing because now I understand how bad that was and what a mistake that was. Now, conversely, I have a lot of patients that rolled in. They're super healthy, 68-year-old guys with PSAs of 20, and they have a bad rectal exam.

And they had a PSA when they were 60, and it was three. And, you know, and they'd come in and I've had a couple of experiences where the spouse is just hysterical because she's like, how could this guy, her husband's internist just stop the test and not discuss it with us? And to be clear, where is the screening recommendation on rectal exam?

Well, it's variable. I mean, I think a rectal exam adds value. Many of the kind of internist societies say that you don't necessarily need to do it. I do think it requires experience, but I think it's part of the physical exam, so you should do it. If you do it enough, you'll get an idea for what's really bad and what's not. And so I have a lot of really good internists that still do it, and they do a great job. And so I think it's regional and it's also barriers by the country. I could probably use a tutorial on it, but I do it a lot and I realize that it's. Can you insert like a zipper?

I'll show you how to do it. Perfect. I want the technique. But I can see that if it's something you're just not doing frequently, if it's something you would only do on someone who shows up with a high PSA, you're not getting the reps. You I sort of know what normal feels like.

What does that thing, what does that 20-year-old prostate feel like? Yeah, you know, you don't need a 20-year-old prostate exam, but you listen to the heart of everybody, and that's how you know when you detect pathology. But in trauma, you got all of those. You did. Yeah. In trauma, you got to see a lot of normal prostate. So, I think that the guidelines have come to a medium. The pendulum was both ways. I think that prostate biopsies are these days a relatively safe procedure. They're not overly traumatic for men. There are some men that have complications. I think that that's a little bit overly dramatized by people who are anti-screeners. The other

thing that urologists are doing today is now doing transparoneal biopsies, so they're not transrectal anymore. So if a patient's listening to this and they need to go and get a prostate biopsy, one of the things I always tell patients is, you should always, you know, it's one thing to know what the average complication rates are.

This risk of infection, this risk of bleeding, it's also important to ask your practitioner, they're personal risks, because medicine is not homogeneous. It's quite heterogeneous. So, what would we say nationally would be the risk of infection or bleeding from a prostate biopsy? Well, I tell people most men have some degree of bleeding after the biopsy.

When you have a bowel movement, there may be a little bit of blood. Let's say bleeding that requires intervention. Right. So, if you talk to, if you go on blogs about non-anti-screeners, they'll say, oh, you know, 80% of men have bleeding in their rectum and 100% of blood in their urine. Yeah, sure. Maybe there may be a little bit of pinkness or redness or if you do a microscopic exam on the urine, there's blood. That's ridiculous. Of course, you can have that. But is it requiring admission to the hospital? We wrote a paper on that

looking in the Medicare age population. The numbers, it's hard because you look at these big data sets, it's hard to know granularity. They say about 7% of individuals will be admitted to the hospital or seen at the ER within 30 days of a biopsy. That number seems high to me. I tell people at our institution we monitor biopsy infections, it's 0.4%. Got it. So somebody shows up at Northwestern knowing that seven out of a hundred guys are going to be back in the hospital a month and you can say actually it's in our hands, yeah, our series, it's forward about a thousand. You feel a half a month better? Yeah, with an infection. I would say that, you know, it's probably about one to two percent

show up at the ER or something for an evaluation. They may be have, because you can have some problems urinating because your prostate can get a little bit swollen. So overall, it's low. You tell them the result. And as you alluded to before, in my practice, I don't biopsy everybody. I biopsy people who I think have clinically significant prostate cancer. So I start with the PHI test. We have it within our system here.

So I use the fork. Is there any reason to switch from one to the other. Are you pretty agnostic? No, the Hans Lillian and Andrew Vickers show that they perform identically in the same serum. What patients, so the fork, K was developed on a cohort of what sounds like pretty homogeneous patients, right? What was the PHI developed on? What was their cohort? Similar. I mean, most of these tests are done and developed in Caucasian men.

You know, I was gonna ask you, do we run a risk here if I have an African-American patient? And, am I, can I be misled by his 4K? Should I be? Well, that's a good question. And the op-go team just published a paper based on a validation cohort of VA patients where there is 50% African American and it performed as well or slightly better.

One of my partners here has a prospective trial. It's him and myself looking at PHI and African American men and they really take home messages. It looks like it performs as well or better. So this is a gift. I mean, you don't normally get this in biology. This is exactly the kind of test that can go awry because you can get fooled by differences. I'll give you an example, right?

You look at non-alcoholic fatty liver disease in FLD. I mean, if you want to study that disease in Hispanics and then try to make even the mildest inference about what's going on in African Americans, you're host. I mean, they're not even the same disease. Yeah. In fact, even diabetes is quite different across races. So to think that something as ubiquitous as prostate cancer, even though it might be

a different disease, because I know that African Americans, we're going to talk about this. I'm sure have a different disease, but even from a screening standpoint that they could be, you could have one tool that is so good in both. Yeah. There is fortuitous. Yeah, they're good tools. And then, so after, if there's an abnormality in the pH, I have four cases where then I moved to an MRI. And then there's been good data.

And can you just, because, I mean, we talk, we geek out on this stuff because I'm super nerdy about what type of MRI to do for what thing. But for a patient listening to this Ted, who's going to go to their doctor and whose doctor is hopefully cooperative enough, what do you recommend? Because not all MRIs are doing the trick here.

Yeah, I mean, on paper, what you want is a multi-parametric prostate MRI, the most important phase, the most important parameter in the multi-parametric MRI is actually to do the fusion weighted imaging, which is the most operator's dependent. So it really requires a skilled technician and a skilled interpreter radiologist

to look at those DWI images. That's the most important one. So we do give patients contrast, but people have shown you can get a lot of value out of just a non-contrast DWI-based. The one we use, no contrast, but it's, the DWI is exceptional. I've sent you the images.

I think if they're shape or approved, I'm happy. They're very good. Yeah, T1, T2, DWI, and Multiplane RMRI. So if you're listening to that, and if your doctor refuses that, I think those are the kinds of things that make me think you need another doctor. Because at this point,

and look, your insurance might not cover it. You may have to put the bill for that, and that's horrible if your insurance wouldn't cover that. That was true, but there's recently reported a large multinational, prospective clinical trial looking at the utility of MRI to use for screening for prostate cancer. The study was half the men got an MRI, and if there's a suspicious lesion, they got that lesion biopsyde, and they increased the detection of high-grade cancer, reduced the over-detection of low-grade prostate cancer,

so it was a quote unquote positive study. We haven't had problems in the Midwest in Illinois getting MRIs approved, but that randomized trial based out of reported out of the UK, that really has changed a lot about what companies are approving for MRIs for screening. So right to here. So if somebody has an MRI, if there's an abnormality on the MRI, I'll recommend a biopsy. Now there's a lot of data that says you shouldn't just sample the suspicious lesion, that you

should do the suspicious lesion plus doing a sexton biopia, kind of what I tell patients is right left top middle bottom, that adds value, not just in the detection of cancer, but if someone is gonna move to surgery, for example, and I don't do a biopsia in a 90 year old guy, even if they have an abnormal MRI, do it if I think that person's gonna live a long, long enough to benefit from treatment.

In those scenarios, I do those systematic biopssy because I want to know exactly where the extent of the cancer. One of the problems with MRIs, it doesn't actually see the true boundaries or true borders of the tumors within the prostate very well. They're often... Especially the DWI because it's not really an anatomic test. The way a T1 weighted image is an atomic. So if you take the lesion on T2 for example,

it often undersizes the tumor by between five and 10 millimeters. So pretty significant for a prostate, which is generally pretty small. So, so I do those to get a better roadmap. I put it all together and then I'll talk to the patient of them what the treatment that should be. So, my algorithm is if you have an MRI done and you have an abnormality, you need a biopsy. If you have an MRI done and it's negative, no lesion, but this is your quiz for the day, Peter, but what is high? Your PSA density is high. So you have nothing suspicious on MR, but a high PSA density, you need a biopsy. And sorry, in that situation, Ted, do you further stratify by 4K?

Well, I have done the 4K or PHI upfront, which is high enough. So you're already talking about a subset of patients who have a high and I think something is going on based on the blood test. Because 20% of time, you're going to use the... 20% of time MRIs false negative. Got it. So now you're using the prostate density. And you and I actually shared an email exchange over this about six months. TSA density is so easy and it is so good. So high PSA density, usually I would say more than 0.15 depends. And sometimes it's 0.1. It depends on the

ages of the patient in their scenario. They need a biopsy anyway. And you know, 20% of time MRIs are negative. But if they have an MRI, no lesion, high PSA, low PSA density, they don't need a biopsy. So we published our series on that. It's not a randomized trial, but what we showed was that when we looked and compared the doctors that used that algorithm and those that did not, you reduced biopsies by about one-third, you reduced detection of low grade cancer by about one-third, and you actually don't compromise the detection of higher grade disease.

So again, we have grade tools building off of this very simple PSA blood test to I think offer people very sophisticated screening for their prostate cancer. We've talked about that a bunch. Yeah, so let's talk a little bit about the biopsy because every patient here who's had a biopsy or knows somebody who's had a biopsy, there's this word gleecin. What's your gleecin?

Yeah, that could be like a t-shirt. So Donald Gleece has need to do a fundraiser here. That could be the urology fundraiser at North. There's a lot of things you could put on t-shirts. Yeah, yeah. I mean, let's take a step back for it. So as you know, one of my best friends from medical school, my roommate from medical school, Matt McCormick, is now an excellent urologist up in Reno. And I just saw Matt a couple of weeks ago, and we were kind of just, we have a patient in common by total luck. So the patient came to see me, and he lives in Reno, and I said, oh, that's so funny. You know, my roommate from Med School's up in Reno, and his name is Matt McCormick, and

he's like, Dr. McCormick is my doctor. I couldn't believe it. Well, what a small world. But I remember in medical school, like one of the things that drew Matt to urology because we all thought Matt was gonna be an orthopedic surgeon. There was just like the most amazing athlete in the history of civilization,

like this guy is gonna be an orthopod because that's what you expect your athletes to do. But then when we all started our doing our rotations, he sort of fell in love with urology and I think a big part of it had to do with two or two things. One was, it's a field where you can't take yourself that seriously. Like in the end, it's a funny, funny field.

Like there's just a lot of dick jokes. There's no way around it. And if you find that, if you don't think that's funny, like you're not going to want to be in that, you got to make it funny. And the second thing was, the patients are so grateful. And again, I think if you're a medical student and you're listening to this, you've got to be able to think about

what kind of patients you want to interact with. That has a lot to do with your chosen profession. I remember there were people in my class who loved being around older patients. And they wanted to go into cardiology for that reason because they're like, look, my bread and butter, the patient I'm mostly going to see is going to be like my grandmother and my grandfather. And that's why I came to medical school, that's what I love and that's what I want to

do. And there's just something about that urology patient. And again, urology is a broad field because there's male urology, female urology, cancer, non-cancer, but for the most part, as you said, you get to fix things in people that are causing them real trouble. And again, I'm not minimizing the stuff that I was interested in, which is like pancreatic cancer. But when you take a person's pancreatic cancer out, they don't necessarily feel any better.

That's true. They usually feel worse because it's a big surgery. It's a huge operation. And it's delightful. I mean, I think that there's a lot of urology that, I mean, look, the patients that we take, the people in urology are great, you know, and so going to work every day is just a blast. I mean, everybody's smart, everybody's fun, they don't take themselves too seriously. That helps.

The patients are wonderful people, they're incredibly grateful. And then urologists also, you know, we own the diagnosis. So a lot of other surgical specialties, let's say colorectal surgery is an example. Very few of the diagnoses come from the colorectal surgeon. And therefore, if you own the diagnoses, you own the pre-treatment, the pre-diagnostic work, you do the intervention and you follow the patient afterward. And so one of the nice things in u yourology is that you have this great longitudinal care with patients.

And so many of my patients followed me from Baltimore. And you know, my nurse Marie, who's fabulous, she hates me because, you know, I'll have like a 15 minute return double book, but it's one of my old Hopkins patients. You know, I'm in the room for two hours. You know, she's like, what were you doing in there? I'm like, oh, we're talking about our kids and the goats and the whatever, you know, and so that part of it really makes it super fun. You know, I forgot about the room for two hours. She's like, what were you doing in there? I'm like, oh, we're talking about our kids, the goats, the whatever. And so that part of it really makes it super fun. You forgot about the goats.

Yeah, I love the goats. Yeah. So I've been trying to get goats. Goats are. I've been trying. I'm not winning. They're not allowed in your town. No, I just, I can't convince the family to get the goats.

Oh my God, you got to go to take me goat, cutest thing ever. They're so cute. They stink, but they're super cute And they're incredibly smart and they're very social so they do not like you can't just get one goat They really they actually they don't they do terribly if they're just by themselves So anyway, so you know, that's the fun part about your allergies You get you know, you get these patients and they all have a mate every I mean I love just talking to my patients

Dr. Walsh he had a way to do a history and one of the second thing he asked is what they did for living. And it wasn't to kind of do a checkbook check. It was just to say how you're going to talk to this person. And for me, I like to ask them that because I love to just learn about what they do. There's so many cool jobs out there. So, you know, sound engineer for a big theater in Chicago at this or that, it's just awesome. Super cool. Yeah, you've had quite an illustrious career that's not even close to being over, which also includes, and I know you don't think much about this, and I think it's more of a nuisance than anything else, but you've also now basically become the urologist to anyone

in power that seems to need, you know, just as Pat was. Basically, when we were at Hopkins, every VIP on the planet came to Hopkins. And I can't, even as a general surgery resident, rotating through urology, I can't believe the people that walked through that hospital, which was also true in pancreatic surgery and, you know, also, it's other surgeries. And so of all of the sort of people, I don't I again I I don't want to use names because I don't know how any of them have ever publicly talked about it. The only one who I know has publicly talked about it is Ben Stiller because of course you and Ben went on Howard Stern together. So how did you even get introduced to Ben Stiller and and I know Ben was very private about this for a couple of years. You guys went if my memory serves me correctly.

It was probably a year or two after his surgery that you guys even went on the show together, right? Yeah, it was two years or so after that, and I met him through his internist discreet. Really one of the best internists I've ever interacted with Bernie Krueger. You're telling me like I don't know who he is? I am, I know, I'm just saying it for the audience. Bernie's great. So for the listener, Ted introduced me to Bernie four or five years ago when I was starting to practice in New York

and he said, Bernie is the best internist I've ever had a referral from. Probably because he trained as a medical oncologist, but he said he's really freaking smart and he knows his stuff and if you're going to be in New York, you got to meet him. So you introduced us. I went to meet Bernie. We hit it off like in seconds. Yeah, and he just said, why don't you just come in my office. And so to this day, I still sit next to Bernie. Bernie's great. So Bernie was taking care of Ben. And Bernie was the guy who did all the right stuff.

He did the blood work. And it was abnormal for him and his age. And got biopsied in New York. And then he came and met with Dr. Walsh. Because Dr. Walsh wrote this, has this amazing book, Dr. Walsh's Guide to Surviving, Prostate Cancer, and Ben had gotten it. And so he came down to meet with Walsh,

but Walsh wasn't operating anymore at that time. And so that's how I met him was through Bernie and through Walsh. I have a copy of the book for you, by the way, because I convinced Dr. Walsh to do a final, you know, an addition of it, just came out in May, it's really, really good. So all the listeners out there, it's a great resource. So that's how he met, and then he had interviewed with a bunch of folks, and he decided to have surgery with me,

which was, I was honored to be able to do, and then he did great, and so he's been an amazing person for the field, because he's not afraid to talk about his journey and what he did, and he really, he's an amazing person, he's because he's not afraid to talk about his journey and what he did. He's an amazing person. He's just a down-to-earth good guy. For me, I view each of my patients as VIPs.

I really honestly, my heart-to-heart do. Yes, I take care of people who are important in many different professions and walks of life. It's fun to help all of them. It's fun to go on Howard Stern with Ben Stiller. That was a great experience. So by the way, it sort of occurs to me when you say this, that you were still relatively junior as a urologist. You'd probably only been out of your training for six, seven years when you operated on

Ben. Did that rough of any feathers at Hopkins that you became the heir apparent? I mean people tell me it did. You know I never really thought about age in that way. You know I've always pushed myself to be the best surgeon I can be and always tried to measure up to Pat Walsh or one of my other mentors is this guy, Bal Carter. These guys were the brilliant surgeons at Hopkins and so to me it didn't matter that they had been doing it for 20 years and I had done it for one year. I wanted to be as good as they were just like you know you were the same way and so that's how I always viewed it right and so and it was just the environment

I surrounded myself with. So for me when when Walsh said, you know, Lus and I want you to become my partner and eventually want you to take over my practice. When I started, quote unquote, as his partner, he was still top of this game and was the man. And I benefited from that because he was so busy, I, you know, he would refer me cases. And at the very end of, you know, our relationship

or time at Hopkins, you know, he wasn't operating more. So if he had patients, I needed surgery, I would do it. And everybody, I think on the outside thought that this is this easy thing, it was a gig. But listen, when a guy you operate on, not only reports to you how he's doing, but how to pow, well, how he's doing, then that's serious, you gotta be on your game.

Yeah, it's like an eternal fellowship that you never left, right? So, you know, he would call him and say, you know, someone so says his incision is crooked. And I'm like, oh my god, you know, so like, you know, you couldn't get, you know, way at anything. And so it makes you better, right? It definitely makes you better. So let's go back to the T-shirt raffle thing. And what's your gleeson? So what is this gleeson score? So Donald Gleeson is a pathologist. He was a pathologist in many people, including the folks at Hopkins, we're coming up with a way to grade prostate cancer.

So we grade cancers, and that's a way to measure how aggressive they are. And usually cancers are kind of high grade, low grade, or a one, two, three kind of system. And Gleason came up with a way to grade prostate cancer based on the appearance of the gland. So if you go back to our analogy or discussion of the sewer system, effectively, you know, there are these channels that the prosthetic fluid comes down and out of. And these channels will grow abnormally in a cancerous state.

And so Gleason was describing how these channels appeared under the microscope. Now one of the interesting things about it was unlike a lot of other cancers where they would describe the grade of a cancer based on a high power view, like a very, very close view, Gleason graded his prostate cancers in a lower power view. So he got a better sense of the... So more of an architecture, it's an architectural thing. So it's the tree, not the leaves. Whereas a lot of grades are the what is the leaf look like? What's the edge of the leaf look like? So so he did it. And so the way he did it was he said, well,

what's the most common looking abnormality? What's the most prevalent abnormality on the view on the of the tumor? And then what's the second most common kind of glandular architecture. And so the gleece in sum is those two things, the most prevalent and then the next most prevalent. And that went from, and so it was a one to five scale. So the lowest gleece in score originally gleece in sum. So there are some ten combinations.

Yeah. The lowest gleece in sum would be a two. The highest gleece in sum would be a two. The highest gleece in sum would be a 10. That was how it started out. But then over time, so meaning a 1 plus 1 or a 5 plus 5. That's right. So over time that evolved in the lowest gleece in sum would be a 6 of 3 plus 3 was the kind of typical read. Meaning because if you're already at the point where you're doing a biopsy, you're not going to see ones. You shouldn't be seeing ones in twos if you're doing a biopsy is that the thinking? I think that There were some general

Organizational architectural features that everybody just agree were low grade not aggressive and Yes, you could occasionally, you know I occasionally even at Hopkins. I'd see it on final pathology or portic leason with some pattern two in it And they would try to explain to me the subtleties of the difference between a pattern two and a pattern three. I think most pathologists call it a they would just call it a three So that's where it was for a long time But there are some subtle differences in the gleeson some that actually have real big differences for the what the patients Outcomes would be And so in 2015, in the late 2014, the International Society for Eurologic Pathologists. So we're talking about DORC Central here.

I mean, you know, real super geeks, but really good pathologists. They are kind of people. They got together, along with Radonks, Radit radiation oncologist, medical oncologist, urologist, and so we need a better way to transmit this information to patients and to intern us in a way they can understand. So now there's a great group. And the great group goes between one and five.

The original kind of old school gleecin' sum of six, that's a one, a gleecin' three plus four equals seven is a two, a gleece in 3 plus 4 equals 7 is a 2, a 4 plus 3 equals 7 is a 3, a 4 plus 4 equals 8 is a 4, 4 plus 5 equals 9, or 5, 5 is a 5. So this stepwise gradation into 5 bins of aggressiveness called the gray group actually translates very nicely into step wise clinical outcomes. So that's the new kind of way that we talk about it, talk about what my patients just the gray group. So you're a gray group one, two, three, four, five.

So do you do any other testing? Do you use like archetype or any of these other genetic testing algorithms to further stratify or do those only become things that are done post surgery to determine adjuvant care. So I think that they can, yeah, that's a good question. So I generally speaking don't, because I think I know what the patient, what they need.

So what are you by that? Well, you taught me when we are interns, you don't order a test, don't do a test unless you know what you're gonna, and yeah, it's so funny, I was just having a discussion with a patient yesterday. Don't order a test if it will not alter your management. Right, so I don't do a prostate biopsy

in a 95 year old guy who's got an L that, you know, I don't do it, you know, so, you know, I don't yourrology consult to the coronary ICU, you know, so I don't do the test unless it's going to change what I recommend for the patient. So prostate biopsy, I'll do it if I think I should change something. So I don't do the test unless it's going to change something I recommend. And for me, there's not many cases where it will change what I recommend.

So meaning, what do I mean by that? Well, again, we don't actively treat all prostate cancers today people who have great group one prostate cancer Generally we recommend active surveillance monitoring the tumor to see if it becomes more aggressive Versus and to be clear these are patients who these are the quote-unquote leason 3 plus 3s That's right and we're saying we, we're going to actively monitor you. And would you just once you have the pathology in your hand, that gray, gray, gray group or the gleece and score,

does anything before that matter anymore? In other words, does it matter in your thinking that this guy had actually 4K of 7.5% versus 20%? Yeah, it does matter. And the MRI results matter. So this is the ultimate Bayesian experience. Yeah. I mean, you know, that's why the genomic test, it's funny.

If you measure and you compare a genomic test and there's a bunch of them out there, head to head with PSA density. PSA density performs pretty much identically well. Right. It's pretty amazing. And do you get the grams? I mean, the MRI does a great job. density, PSA density performs pretty much identically well. Right. It's pretty amazing. And do you get the grams? I mean, the MRI does a great job at doing the volume. Do you get that? Can you get that off ultrasound? A question hasn't MRI. We measure the ultra at the time of the biopsy will measure it, but the, you know, generally speaking,

we get it off the MRI is what I use. So at least in six, I generally recommend surveillance and less than super high volume six. And I know in my brain that, and that's independent of age. So, a gleece in six, I generally recommend surveillance unless they're super high volume six, and I know in my brain that, and that's independent of age. So, a 40-year-old, I mean, we have a mutual patient who was a gleece in seven, I believe, at the very young age, like 45, correct? Yeah. Did his age being 45 versus 65 change the way you managed him? Well, so he came in with a single core seven and really wanted to do surveillance. And that would be one opportunity to say, let's do a genomic test on this on this individual

and let's see how aggressive the tumor looks under the, under the true microscope, the molecular profile of the tumor. And so we talked about doing that and his biopsy, the molecular test was favorable, but you don't forget about those patients, you actually follow them active surveillance. So we rebiopsyed him after a repeat MRI, and he had a lot more. His MRI was actually pretty favorable. This was an MRI and visible lesion,

and he had multi-core seven. So we then, we took him to surgery and he did very well. Yeah, I always think of his case as just one of those examples of, I don't know what the term is, because I don't want to use the term precision medicine because that's become so stupid and meaningless. And I don't even want to use the term multidisciplinary, because it really wasn't multidisciplinary.

It was mostly shape or disciplinary. But it, I guess it's just the nuance of the field. It's just, that's the medicine, that's right. Yeah, that's the, nuance of the field. That's the medicine, that's right. Yeah, that's the hard part. That's the part that you don't necessarily figure out in residency. It's so easy, I think, to go through residency, learning the technical stuff, learning the surgical judgment.

What do you do if this person's got a postoperative bleed versus an infection? Who do you sit on? Who do you take back to the OR? Those are very important skills. But this is like kind of next layer judgment stuff that, I mean, aside from talking with your colleagues and surrounding yourself by people who are, you try to surround yourself by people smarter than you, how do you continue that evolution of learning? We have a, what I call, adult only journal club every Friday, every other Friday morning. So it's all the oncologists in our group, medox,, radonx, urologists, urologic oncologist. And I call it adult only because

it's not really for the residents. It's during their teaching conference. And we just pull articles that come up every day. So every Friday morning I get a feed from the NIH about new prostate cancer articles, any article with prostate cancer in it, I get that link. It's about 180 to 200 papers a week. I review that list and anything that looks good, I pull it and I'll look at the abstract or I'll pull the paper. And so I send those to the group and on Friday,

two days from now, we'll go over my prostate articles plus my partner's bladder cancer articles or kidney cancer articles, because I don't read those. So I have them tell me what's important in those fields. So that's how I, it's really fun, because it's just like, you know, what we, it's being in school again. It's being in school.

It's this idea of continuous learning. So that's how I think about it and try to keep on top of it. Meetings are okay, but you know, I think that people get bogged down in just the politics of a meeting, so I think reading is what I try to do most of. So let's pivot to another topic that's germane to prostate cancer, which is kind of a two topic that goes hand in hand. The first is the role of testosterone.

The second is the role of dihydrotestosterone. So we can explore this in any order, but I want to definitely touch on the notion that is there a real or perceived effect of patients who are on five alpha reductase inhibitors? So for the listener, males make a hormone called testosterone. Testosterone is converted via an enzyme called five alpha reductase into a very similar molecule called dihydrotestosterone abbreviated DHT. DHT is actually a slightly more potent steroid and in men who...

Fifty times more potent. Yeah, it's a big deal. In men who are susceptible to baldness, DHT drives that process. DHT also probably plays a role in the enlargement of the prostate, is that correct? Most of the 5-alpha reductase enzyme is in the prostate. So, yes, reducing allergens in the prostate by effectively reducing DHT production reduces the size of the prostate. So, a lot of guys take medication to reduce DHT

either to reduce prostate volume size, so something called benign prosthetic hypertrophy, or to minimize hair loss. And it's usually the exact same drug given it's slightly different doses. And then sometimes you even come up with different names for the same drug. So, proscar is,

finastered at five milligrams, and I think propitia is the one milligram. That's right. Okay, now I remember many years ago, and I'm sure this has been revised a hundred times, but maybe 10 years ago, maybe less. But a paper came out that said, look, in guys

who have suppressed DHT levels, when they get prostate cancer, they're more high grade. Is that, am I remembering that correctly? Yeah, there's been definitely case reports of that. It's hard to really study that over a big deal. I got it. So what is the current thinking on five alpha-productase inhibition and that relationship to prostate cancer. Well, there was a very large randomized trial to see if you could take that medication

with the idea that if you reduced the relative amount of allergens in the prostate by preventing the production of this potent allergen, DHT, could you reduce the risk of prostate cancer in those men? And the answer was if you took that medicine that reduced potent and energy that you could, so there was a, oh, the study. I'm sorry, this was in men starting out who did not have cancer.

That's right. So it was called the prostate cancer prevention trial. And it was over seven years that the trial was conducted. Ian Thompson was the PI on the trial as a big study. It did reduce the chance that a man would develop prostate cancer over a, you know, a reasonable amount of time. But one of the problems was that there was increased detection of more aggressive cancers in the men who are taking the finasteride. And so then the question was, well, what is that from? Is it inducing a more high grade cancer, you know, and whether or not that's true or not is it selecting for it

because any cancer that comes out of a low DHT environment? Well, yeah, so I personally think that what you were just saying is true. So yes, and there's case reports that people with low testosterone or for example, people with low PSA's because PSA is only made when there's testosterone around, for example, that those individuals have more aggressive cancers. Now, this is what I've been focusing on in my lab for like the last four or five years now. the cool things we did in this collaboration with this company Genome DX and this great scientist, Eli DaVincioni, was to look at the biology of prostate cancers, how aggressive they were, and compare the aggressiveness of the prostate cancer with the

androgen output of the tumor. Another nuanced way to normalize things a bit. Yeah. And so we had this hypothesis that the tumors that had the most amped up energy signaling, the most energy in output because prostate cancers are energy in urban tumor that they would be the most aggressive. And I say it that way because you know the answer is the exact opposite. The tumors with the lowest energy in output where the are the most aggressive tumors. So it somewhat relates to PSA, but not entirely like there's not a true linear correlation.

So the high androgen output tumors, they can be aggressive, but they are not as aggressive as the ultra low one. So it's this bi-modal distribution. And this is a good way to segue talking about these molecular tests because this is a commercially available test from Genome DX.

Can I tell a funny story about Eli before we go down there? Sure. I've told this story before, but now we get to put a name to it. So I hope he doesn't like, like I hope I don't upset him that I'm telling this story.

It was, it was, it was Eli's the guy who called me one day when I was in the airport. And he's like, here, my wife just got me this book. It's a great book and you're in it. And I was like, what, I had no idea what he was talking about. And he goes, yeah, it's called biggest tools.

And I was like, wait, do you mean tools of Titans? He goes, yeah, yeah, yeah, yeah, that's it. That's great. I know I have to make stories. So to this day, anytime I'm talking with Tim Ferris, I'm like, I expect to be referred to as the biggest tool. I love that story. He called me too. He's like, dude, I'm reading this book, but he didn't call it biggest tool. That's awesome. That's really funny. So Eli started this company that was, you know, genomically transcriptomically.

So looking at the RNA levels within prostate cancers. And so he has a commercial product that's very, very good to just tell you the aggressiveness. It's basically a genomic leason score. It's more sophisticated than that, but that's effectively what it helps you to do. But when he looks at each tumor, he captures about 1.4 million data points on each tumor.

He uses 21 of them for his test, but we use the other 1.39999 million of those data points. And so we developed this algorithm to look at this. The thing that's pretty cool is we've been able to model and show with Eli's group that, you know, because it's one thing to have a kind of prognostic biomarker like your prognosis is good or bad, but precision medicine is really the kind of the predictive stuff. So we've been able to take all this data. We've been able to show that these low-androgen output tumors are the most aggressive tumors. Now high-androgen output, very high-AR output tumors are also aggressive, but as you would imagine, the tumors are sensitive to different drugs.

So a high AR output tumor, they're exquisitely sensitive to androgen deprivation, which is one of the mainstays of treatment for metastatic prostate cancer. Low androgen output tumors are not, right? They're not dependent on it. They don't use it as their fuel for growth. And we've been able to model other compounds that they are sensitive to, and so we're moving those things into clinical trials.

It's actually pretty exciting times. So what is the current state of the art, or the current thinking on testosterone replacement therapy? And again, I'm referring to this in the confines of what we would call physiologic testosterone replacement. So you've got a guy who's walking around with a free testosterone at seven nanograms per desolator on a lab where the upper range would be 25 and, you know, he's replaced to 20. My reading of the literature says I'd have a very hard time making the case that's increasing

his risk of prostate cancer. I agree with that. And I think my data suggests that the tumors that, you know, we don't know how they develop, but the tumor, we segwayed like five times. But the idea is that our data shows us that the most aggressive tumors are the ones that have low, androgen output. Now, does that mean that they developed in a low, androgen state?

Maybe. We don't know. But I mean, we don't know. But for sure, it's telling me that I don't, and like you said, I mean, the literature that we've discussed on the phone many times. I don't see any clear evidence that physiologic replacement of testosterone is going to accelerate or cause a cancer to develop. What do you think the role is of estradiol in this?

Some have argued that as estradiol is going up, that may be playing a greater role in prostate cancer, either through its direct interaction or indirectly through its receptors. I think I don't know the answer to that question, but I do know that it's not just a testosterone thing. Remember, when we just talk about benign neurologic conditions, testosterone values decline over time, And I oversimplified the whole PSA discussion earlier. So remember that PSA's rise over time, but at that same time, testosterone values are declining. So I do think that a lot of the prosthetic growth, not cancerous growth,

necessarily, but but nine growth are influenced by the ratios of T to E, so to speak, testosterone to estrogen's, you know, androgens to estrogen's, which one is that because it seems to me that you're at your highest risk when your testosterone is going down and your estrogen is going up. Yeah, now the question is what's the lag time? Yeah. So in real time, yes, that's true, but we know that all cancers, prostate cancer for sure among them is Something that occurs from mutations of the DNA from decades prior probably so yes at the time of diagnoses There's probably higher estradiol lower T

But I think about it like well what happened to that in that patient 10 years beforehand or 15 years Is there anything about the mitochondria in the process? I mean the prostate has so many odd things about it And we're gonna talk about it the difficulty with immune surveillance in a moment But is there anything about the the mitochondria within the prostate that are unusually sort of either ramped up or ramped down relative to other Epithelial cell derived tissues. Yeah, it's a great question. And I hope you know, I try to ask great questions here. I say that because we just had last Saturday, we had our kind of a prostate cancer working group meeting where all the kind of deep thinkers get together, we got together on a Saturday.

Yeah, it's just about to say the fact that you guys do this on a Saturday is just another bit of evidence to like the level of obsession here that I love. Yeah, so we, I re-roped in this brilliant radiation oncologist named David Gaius. He works on hormonal dependency and breast cancer. And what he focuses on is on the mitochondria. And specifically, these superoxide disc mutases that really get rid of reactive oxygen species. And so he has a whole model and he knows about luminal B breast cancers and how they can become resistant to moxothin and so forth. And it's driven by basically the mitochondria. And so...

In the mitochondria, in the prostate cancer, follow the warberg effect. Do they become more... do they favor anaerobic metabolism over oxidative phosphorylation? You know, it's hard. People don't we don't know. You know, people don't know a lot about the metabolic environment of the prostate. I've had a lot of thoughts about where to say what about the, I mean, it's a, it's a very dense organ. There's not a lot of blood vessels in it, it's not a big blood supply. You know, and so I've thought a lot about just, for example, are there regional differences in the pH within the prostate and is that? What's causing these, because I think about it in relationships with these androgen dependent

tumors, my brain is defaulted to this idea that, well, the high AR output tumors are ones that are occurring in oxygen-rich parts of the prostate. I mean, I don't know why, just assume that, you know, and that these lower AR output tumors are occurring in regions of the prostate. They have lower PAO2s, different pHs, and they're forced to use an alternate growth pathway. It's hard to test that, you know, I've thought a lot about it. There's nothing published on it, really. It's hard to test it, but this guy, David Gaias, has a lot of really

interesting data looking at the Sertunin pathways through mitochondria, regulating the hormonal dependency or hormonal regulation of prostate cancer. It's a brand new area for him. So in other words, the Sertunins, which of course can either turn on or turn off genes. The idea is, and this is sir two or a different sir three, sir three. I see. So it could be up regulating or down regulating energy and production basically. He has a sir three manganese super oxide dismutease pathway worked out and it regulates resistance to to mox, if it illuminable, be breast cancer. So, and he's made these observations. He first published this in cell,

and I want to say, 0708, on Certunin III in breast, but he's had some data in there in prostate. So, I kind of, I hang out with them when I want to hang out with like a deep thinker. So, he has this preliminary data, and he has some more interesting data that there may be a role for this.

So I do think that there's something about metabolism in the prostate, I think it's hard to study. You know, it's tough, it's hard to model that in a mouse at all. Like you can't do it, you cannot model in a mouse. I do think that there's some good people on campus here who think about it and are gonna to be able to study it. Well, he's the guy.

You know, I'm seeing Nav Chendell tomorrow who is a mutual friend. Didn't you go to med school with that? I mean, you were, he was in grad school when you were in med school or something. He says that he was my TA in undergrad. But I just know, you know, known him, I think we figured out I've known him in 19, I met him in 93 or 94. So he's really one of my oldest friends I have, you know. Anything I should know about now? Well, I mean, I know him, of course, because we played petticakes on Easter Island for a while. And well, do you know

what his nickname is? No, that's a thing. There was a nickname. Yeah. What's his nickname? Well, just for the listeners, Navdeep is this, he's about what, six foot three. He had a very suave, good looking guy long hair. So his nickname was swab deep. I've never seen a TA class where there was, it was like 90% women, you know, had questions for him afterward, you know. He was awesome in med school. He's great.

And did you also go to school with Matthew Vanderhiden? I did. He was a smart kid in my med school class. Yeah, Matthew's, I And did you also go to school with Matthew Vanderhiden? I did. He was a smart kid in my med school class. Yeah, Matthew's, I mean, I know Matthew, obviously not as well as you, but he's... I don't know in that well. I just know him and now really broke up in the field of cancer, metabolism.

Yeah, I'll be, I gotta get out to Boston to see Matthew, who actually works and collaborates very closely with another very, very close friend of mine from medical school named Mark Palmerance, who's a medical oncologist Yeah, Mark. Yeah, he's great. I love that all like all of these independent circles of my life have overlapped in prostate cancer and cancer in general Yeah, what is the most exciting area of research that that you think of with respect to prostate cancer specifically? Maybe I'll even prime the question by saying

specifically. Maybe I'll even prime the question by saying, immunotherapy seems to finally be coming into its own a little bit with some cancers. But of course, the prostate's kind of a weird, immune protected, odd organ. Like, does immunotherapy play a role in this? Or are we talking metabolic therapies? Or is it all going to be coming down to earlier detection of lethal cancers? Certainly, early detection of lethal cancers is important. I think the most exciting stuff in urologic oncology is really moving beyond these prognostic biomarkers to predictive biomarkers. So, there's a lot of really cool new things that are great. So there's some predictive biomarkers that you can pick up in the DNA of a tumor,

or the DNA of a patient, particularly, BROCA1, BROCA2, ATM loss, these different kinds of DNA damage repair pathways that people didn't really think matter for prostate. We now know, within the last three years, that they really matter. So that's news to me. I never really understood that BROCA1, BROCA2 should be looked for in males as well. I mean, I did from a breast cancer standpoint, but not from a prostate cancer standpoint. Yeah, so there's one of my heroes in neurologic oncology is this guy Pete Nelson. He's at the Hudge in Seattle. And he published a paper and they looked at the germ lines of men with metastatic chastrate resistance at the most end-stage prostate cancer.

And what they showed was that in contrast to the general population of men, that mutations in these different DNA repair pathways were significantly enriched in individuals who had metastatic prostate cancer. So about 11 to 12% of men with metastatic castrate resistant prostate cancer had mutations, particularly Brocka 2, Brocka 1, ATM, Rad 51, these different pathways that are involved in DNA damage repair.

If you look in the tumors of men with metastatic cancer resistant prostate cancer, it, depending on where you look, over one-third of the tumors, the cells will have mutations in these pathways, which makes them incredibly sensitive to part inhibition. So that's a huge game changer. The other thing that people now look at is kind of the total genomic score or the alterations in the genome of the individual cancer cells, and will that make them more sensitive to immunotherapy or not?

That's more coming online. But the idea that there are things in the somatic DNA of the tumor cells and in the germline of individuals that you can use to screen for not only prostate but breast, pancreas, etc. That's a huge game changer. And then as we touched on earlier, those are not just prognostic biomarkers, but they're predictive of drug response, which is pretty amazing. And then I think Eli's test the version 2.0 or the beta version of it, which has a lot of these built-in biomarkers that predict response to drugs that now are being tested in clinical trials with the idea that let's test the ability to predict response.

It's pretty amazing stuff, actually. So obviously you specialize in prostate cancer. The field of urology is so much bigger than that, right? We haven't even talked about renal cancer, bladder cancer, and to do so would only be to do it in injustice. Given that we've been talking for a little while, and I know you've got a hard stop here in about 20 minutes, I want to talk a little bit about benign stuff. So I'll tell a very personal, maybe, somewhat embarrassing story, but it's a good illustration

of this. So, probably. I want you to read it at the extra large penis clinic. That happens. There's a micropeniscus. The peniscus surgery? Yeah, the peniscus surgery. Yeah, the peniscus surgery.

Yeah, exactly. Those are the kind of jokes we can only tell in the year-old. Yeah. Yeah. So, about two years ago, I remember calling you and I was like, Ted, I don't know what's going on, man. Every time I pee, like it's just burning like crazy, I did a quick check, I don't have a UTI, I've never had a UTI,

it seems unlikely I would, I've been fumbling around and I'm wondering, I must have prostititis, right? And I guess my question is, Ted, what antibiotic should I take? And I remember I was actually in Baltimore at the time, but I was heading up back to New York, because I was going to work in New York that week where I spent quite a bit of time.

And you said, well, first of all, you're in luck, because my dad wrote the paper on prostitutitis. And I forget what year it was, but it was in the England Journal of Medicine. And I downloaded the paper, and I read it on the train ride up to New York, or maybe I was still in Baltimore, because I remember you had, anyway, you'd written me for some flow in my expel, but the long ride up to New York, or maybe I was still in Baltimore, because I remember you had,

anyway, you'd written me for some flow in my expel, well, the long and short of it was, I came away from reading the paper and I said, well, my takeaway on this is I need a prosthetic massage, not an antibiotic. And you said, yep, so go ask Bernie to give you a prosthetic massage. And I had been in pain for a month.

And he did that to get a sample from the prostate. Because when you do a urine check for an infection, you're sampling predominantly the fluid, the urine in the bladder. So I said, yeah, find your urine culture is negative, but let's check your prosthetic fluid for an infection. I think it was clear, but it was clear. And here's the amazing part of the story.

I had been suffering for a month. And Bernie being the great Bernie. Like he didn't just give me a little bit of a prosthetic massage. I mean, he eviscerated me. It was one of those Chevy Chase moments where I was like using the whole fist there, Doc. Moon river. Actually, I will say it was one of the most painful things I'd ever experienced. I just, this was a different level of pain because it wasn't the rectil it was like the prosthetic massage to generate the furious. Very sensitive. Yeah, especially when you're inflamed as I would later come to realize, well, here's the most amazing part of that story.

Within about three days, everything was better. I didn't need a single antibiotic. And somehow that massage probably somehow turned over some of that inflammation or, you know, there's something, yeah, I mean, we had you on some anti-inflammatories and we had you on some other symptomatic stuff. But yeah, I mean, it definitely, you know, so we don't really call it prostititis anymore. It's kind of been into kind of this chronic pelvic pain syndrome kind of concept. But within that concept, you can get acute bacterial prostatitis.

That's what happens for people after prostate biopsies. And they get very, very, very sick. High high fevers, 103, 104, like, you know, bad stuff. That's an incredibly rare thing. But what you can get is basically non-bacterial prostate, inflammation in the prostate. That's the thing I think a lot of people don't understand. Itis means inflammation. That's right.

You can get itis with an infection, but itis does not imply inflection. So prostate is mastitis. These things don't necessarily imply that there's a bacterial infection. It can be sterile. Right, so people will have acute inflammation in your prostate, which is what I thought you had on the phone.

I said, look, have Bernie do an actual culture of the prostate. Then typically for most people that goes away, we don't know what causes it. We don't know what is that's causing that inflammation. That's what my father is a very prominent researcher in this field, that's what he works on. But we know we can we try to treat the symptoms and ride it out. And then we you know and then we try to adjust risks that you know we prevent it kind of from

coming back and so forth. So some of the things that can cause it, you know we talked about this you know constipation. So if you one of the ways it's easy to get constipated is just going to a transcontinental flight because the air is dry and you ways it's easy to get constipated, is just going to a transcontinental flight, because the air's dry. And you know, it's just, those little subtle changes make a big difference. So, so those things coming to play now, that falls within this greater scope

of something called chronic pelvic pain, which is a, I know, a field that is, you know, has some work in it, but it's still evolving. It's really just been recently described. My father was one of the people described. That was some other folks. And so that involves just burning or pain in the urethra and the bladder.

Women, it used to be called interstitial cystitis in women, so some foods will trigger these things. We don't have a good handle on it at all. So we try to manage the symptoms. And then from there, we try to just prevent. What's the state of the art with using injections within the bladder of Botox to alleviate women who have interstitial cystitis? I don't think that's a discussion about that. Yeah, it's not, we do, we use Botox in the bladder for people who have hyper-contractility of the bladder, but we don't use it for people who have interstitial cystitis.

For people, there are people that have deep-seated infections in their prostate that we can document, or sometimes we can't document, but we have a suspicion of them. And in those individuals, you can actually directly inject antibiotics into the prostate, or in fact fact my feeling is that actually the typical nitis for this persistent infection is actually the seminal vesicle, which is attached to the

prostate. So what you know, we'll have these individuals who have recurrent bacterial infections, same bacteria, same sensitivity to the drugs, so they don't become resistant. They're equally sensitive all along because there has to be a bacteria that you aren't clearing that's outside of the field of scope. That's right. And so, and I feel like those are often or you can you can't get the concentration high enough into that tissue. And so there, those cases will do. So how is it difficult? You do that trans rectal, trans rectal, your panion, but it's,um, but it actually works under all the sound guidance. And how easy is it to hit a seminal vesicle? Super easy, even you can do it.

Even I could do it. That's hard. Let's do it. Let's go across the street. I was gonna ask you about that. So thanks for bringing that up. I was gonna ask you about the interminestatic injection. You should do it.

You need to do come do a share day with me. Wouldn't that be awesome? It's so much fun. You've never actually been on the robot, have you? No. We gotta do it. Oh man. How many?

Yeah, going back to that for a second. So, I mean, we didn't really get into the deep surgical technique, but I do want to link to any videos that we can, but what percentage of your prostatectomy is do you now use the robot for versus open? 100%. You're 100% robot now?

Yeah. And Mo's 100% robot, obviously. So most men now getting their prostate removed, we'll do it with the robot. I mean, I think that there are very few people out there that actually can comment on which one is better, robot versus traditional open. But I've done, I don't know, 1,500 opens and 2,500 robots.

So I have a good idea for which ones are better. And it was the last time you did an open case? Mm. Three years ago, two years ago. Is there a party that's sad that like, if you went back and did an open tomorrow, you wouldn't be as good? I wouldn't be as good, but even when I was good robots, I'm better using the robot.

It's just incredibly precise. I'm just a super type A guy, you know, you get four arms to control. I only got two hands, right? So you can just retract everything exactly where you want it. The magnification, the optics are just unbelievable. And you would just die.

It's just like, where? It's still the da Vinci. Yeah, it's like we're in 20 X loops. You think about it, you know, you had the 2.5 that you still walk around with. Hey, hey, hey, I upgraded to 3.5. Those are tough. I had some 4xs and it's harder, but it's amazing, right?

Well, it depends on the case. Yeah, but even anything, I mean, I wear my loops for every open case I did. But even the difference we did in 2.5 and 3.5 is a big difference. So think about 10x. I just put a 4x magnifier on my bow. So you have a clarifier in that sits in the peep,

and then you have a magnifier that sits on your scope. And I've been shooting probably up to 70 yards naked, and then I went to a 2x, and I was like, oh, this is good. And then I went to the 4x. And I just don't know if I could ever go back. That's the thing. one of my mentors, surgical mentors is this guy, Bal Carter. And he always did his cases without loops.

And then Pat made him switch. And so we would talk about it. And he said, you know, it's just literally a different operation. And so people who do open prostates without loops, I don't know what they're doing. Because I mean, you just see everything, right? You see it all.

Now, think about the robot. I mean, I can dissect out individual little arteries that are one, two millimeters. Has this made it difficult to teach residents? Mm-hmm. It's easier to teach them. You got to come by tomorrow, doing a case. Seriously, I'm talking to Nav tomorrow. I'm not supposed to do that.

Nine at 7 a.m., that boy doesn't roll out of bed before nine. I'm about to take you up on that. Yeah. There's a lot of other stuff I want to talk about. I know we're getting real close. You've got a hard stop in 10 minutes now. Do you know anything about male contraceptives? Is this a topic that is there a male contraceptive on the horizon outside of a vasectomy? I mean, the only way to really prevent sperm production is to block testosterone and the testicle. So that's the way to do it. And, you know, there's a couple that are coming online. They've been tested in smaller groups of men. I don't know if they're really

ready for prime time. And I don't know if men are ready for that. You know, what about best sector means? They work. What's the reversal rate on them if you need to worry about that? Well, I mean, I have a partner here, Bob Ranagan, who's, you know, he's one of the, he's one of the top three guys in the country and, you know, Yeah, if it's the right, if it's the the the sector, he was done correctly the first time, you know, by a professional so to speak. So not in the parking lot. There's there's a surgeon. I'm not gonna be my professional. Who else is doing fast sector? He's out there. GB. There's a guy who just think about there's a guy off guys, you know, I'm not gonna be my professional. Who else is doing fast-sector? He's out there, G.B. There's a guy who just think about,

there's a surge in that. I got off guys, you know, I got, yeah, yeah. Okay, I'm not saying he did him, but if there was a urologist like him, yeah, yeah. Nickname, Hodead, hands of death and destruction. Anyone, any Hopkins resident from our era listening to this knows exactly who we're talking about. That's right. So as long as you don't have a hoedad, you can, they can be reversed,

but the reality is that- That's what 80% 90%. The patency is, yeah, I think it's over 90% for a, well, a good microvascular- So if you're a guy who's deciding who's sort of waffling on this, it seems to me that donating a bunch of sperm, putting sperm into a bank, having a really good person do the bestectomy is a surefire way to just go ahead. I mean, most of the time, you can have, I mean, the reproductive technology is just ridiculous. So individuals who have client filters,

where they really almost have no sperm production who were told 10 years ago, you can't have a child. Now you can do these procedures under the microscope where you can find individual nest of sperm within the testicles of these men. And you allow them to have kids, which is amazing for them. I had no clue someone with client filters could do them.

And then of course, you're doing it anyway because you want to be selective for, you know, that's right. You're getting the right chromosome. Right, so I mean, I think there's nothing wrong with this. And then of course you're doing it anyway because you want to be selective for you know right? You're getting the right chromosome. Right. So, I mean, I think there's nothing wrong with this. I mean, it's a very effective way to do contraception. I think, you know, if you're single and you're dating around, I think you should also use

protection, not just contraception. So to me, this will be our public service announcement, not to be confused with the other PSA. This will be the shape for PSA on Eric Condom. Yeah. I think not just for protecting or not having children, but for all the other reasons to do it. Is there anything else that we can talk about in five minutes

that's not going to get one of us in trouble? Well, there's lots of fun things that we can talk about, like watches or pens or cars. Yeah, you and I have shared that from the beginning. And this isn't going to work because you're going to cut it. All right, so on each of those, if someone walked in the door today and said, Ted, I'll buy you any watch you want. Within a reasonable price frame, don't just pick the most expensive watch.

But is there a watch you'd love to just have sitting on your desktop when you walk back into your office courtesy of some Santa Claus. I notice you're wearing a beautiful Hulk today. I do. I wear that on my non-clinical days. I do like it. I didn't wear it a lot.

I would say, I'm in the market. See, this is I always just ask you. I'm in the market for an elegant dress watch. I've never, that's the thing. I have to say that, you know, I'm pretty satiated for watches these days. I'm good, but I don't know. I want to elegant dress watch,

but I could travel with it and it would have GMT. That's my challenge to you. Oh, for heaven's sake. You had to throw the GMT. So because I want to be able to wear a dress watch to a meeting and I want to be able to go to the meeting, change my time zones. You know, I want to go to the meeting

and now have nobody know what the watch is, right? Because you know, yeah, I can get that in a Rolex or whatever, but it's, you know, it's sometimes it's nicer. It's nice. I will take this on as a personal challenge. If you're willing to give up the GMT, I'm really, I don't have it, I might never have it, but I'm really obsessed with two Vacherons out there one is the ultra thin and the other is the 1921

Which is a remake of the famous driving watch Yeah, those would be but you know, you're not gonna get a second time zone on either of those I just think you know, you travel a lot too, right? It's so nice to just know where your time zone is at home And that's what I like about that. I like that. That's my newest thing. I love that. So I'm looking for a GMT watch because that to me is like so important. So if you could get home to San Diego and find any car in your garage, what would it

be? That's a tough question. And I assume you mean a car that will only be driven on the street is not going to be on the track. I'm not taking it to the track. This is for you, for San Diego. You know, you've definitely got me more and more interested in Porsche. And I think that the 911 Turbo, you know, so when that, I don't know, let's just say I

could, if I could get an early jump on a 992 911 Turbo, that might be. Yeah. That's a great vehicle. That's a well engineered. I could if I could get an early jump on a 992 911 turbo that that might be yeah, that great vehicles that Yeah, they're really special cars and they're so drivable. I mean there are other cars that I know you and I have driven We we have friends who have beautiful cars that have given us their 488s and 458s and all those things and they're they're incredible I mean I actually I love the 458 But you just you're not gonna drive that car every day. And there's something else that comes from it,

which is, I guess I just deep down, always feel a little self-conscious, pulling, you know, driving around in the bright red Ferrari. And I don't think you feel self, you don't think you just, you don't have that same level of being self-conscious, driving around in certain other cars. But that said, you know, the 488 is a blast.

So you have a fit in it. I have a long torso. Yeah. And I can't get the seat right. So I'm not looking at the head, you know, the headwreck, the A pillar. Yeah. So, but it's a great, it's a great car. And there are great cars out there, but as a daily, you just can't, I mean, I, you know, that 911 turbos, they're pretty amazing. Yeah, I've never actually driven a McLaren. I don't know if you have it, but I've heard those are really fun too. I have a couple of friends that have them and I always have an open invitation to go visit them

and drive their McLaren's in other cities and those look like really special cars. But part of that's emotional too. I think you should have an emotional connection to McLaren because of Santa. Yeah, so. I don't like the Santa though. I don't like the looks of that car. Oh, I think that thing's gonna be just a beast. I think it's having an emotional connection to McLaren because of Senna. Yeah. So. I don't like the Senna though. I don't like the looks of that car.

Oh, I think that thing's gonna be just a beast. I cannot wait to see it before. It's a beast, but I mean, it just, I don't, you know, I like the functionality that they put in their cars. Do you think that the Senna looks better or worse than the P1? I think the P1 looks better,

but I haven't seen either of them in real life. I've seen a 720 in real life, cool car. Real cool. The Aero. The, 20 in real life, it's a cool car. Real cool, the arrow. The arrow, when he's look great. The arrow in that car, it's cool. I saw a P1 in person once in New York City of all places, which I've never understood that logic. Yeah, right.

What would possess you to, it wouldn't matter how much money you have, what would possess you to drive a P1 in Manhattan. Yeah, it's crazy. It's just like a Tom L. It's it. I knew somebody who had it had a law had a 918 and a P1

And he saw one of the three because he said it just wasn't fun to drive around Let me see if I can guess I don't know. Maybe the La Ferrari the P1 P1 because it's just too much of a race car So he said that you just you know on the set on the track. It's just ridiculous but the we he said that he sold it because on the streets it just, we couldn't even begin to enjoy it. Wow. It's so cool though. I actually think all of those hypercars, like I love watching Chris Harris take those cars around. So for the listener, certainly the last generation of hypercars were those three cars. The Ferrari LaFerrari, the Porsche 918 and the McLaren P1. Only one of them ever broke a minute 30 on Laguna Secca.

Do you know which one? I would guess the P1, but I don't know. No, it was the 918. Went one minute, 29 seconds, 0.89 seconds. By 111, I'm the service second. The 918 broke a minute 30 on Laguna Secika, the only production car to ever do so. Now, my favorite little tidbit. And I'll tell you, so the 911 Turbo S is faster

than a 918 at the ring. I know. So unbelievable. Unbelievable. But then of course, there are $50,000 track cars that'll go a minute 19 on that Laguna Psycho which again is always the great thing for people to understand the difference between track cars and street cars.

Yeah. Ted, this was awesome. I know this was a bit more of a male centric episode but I think one guys will get a lot out of this but also I think you know for women who know a man who's going through this or will go through this. I mean I think there's a lot here and we'll be sure in the show notes to link to a ton of the stuff that was discussed. It would be great to be able to link to any videos that you have on your surgeries.

If people want to learn more about you, I mean, obviously at Northwestern the website will link to your bio, your CV, and all that. I think Google, Dr. Edward Shayaefer, they'll get all the links. But NM or Northwesternmedicine.org is a good way to find me. dr-shaefer.com is another way to find me. Okay, do you do anything on social media? I'm, my handle is at Edward Schaefer. Okay, cool.

Ted, this was awesome. Thank you for making the time and for your hospitality with insights. Yeah, thanks for having me, Peter. You can find all of this information in more at peteratiamd.com forward slash podcast. There you'll find the show notes, readings, and links related to this episode. You can also find my blog at peteratiamd.com. Maybe the simplest thing to do is to sign up for my subjectively non-lame once a week

email where I'll update you on what I've been up to, the most interesting papers I've Com. Maybe the simplest thing to do is to sign up for my subjectively non-lame once a week email, where I'll update you on what I've been up to, the most interesting papers I've read, and all things related to longevity, science, performance, sleep, etc. On social, you can find me on Twitter, Instagram, and Facebook, all with the ID, Peter, ATF, MD, but usually Twitter is the best way to reach me to share your questions and comments. Now for the obligatory disclaim. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional health care services,

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