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

00:00:00.000 Hey everyone, welcome to the Peter Atiyah Drive. I'm your host, Peter Atiyah.

00:00:10.140 The Drive is a result of my hunger for optimizing performance, health, longevity, critical thinking,

00:00:15.600 along with a few other obsessions along the way. I've spent the last several years working with

00:00:19.840 some of the most successful, top-performing individuals in the world, and this podcast

00:00:23.600 is my attempt to synthesize what I've learned along the way to help you live a higher quality,

00:00:28.360 more fulfilling life. If you enjoy this podcast, you can find more information on today's episode

00:00:33.000 and other topics at peteratiyahmd.com.

00:00:41.420 Hey everybody, welcome to this week's episode of The Drive. I'd like to take a couple of minutes

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00:04:01.960 thank you for taking a moment to listen to this. If you learn from and find value in the content I produce,

00:04:07.240 please consider supporting us directly by signing up for a monthly subscription. My guest this week

00:04:12.980 is Dr. Ted Schaefer, the chairman of urology at Northwestern University in Chicago. He's a urologist

00:04:18.400 who specializes in the diagnosis and treatment of prostate cancer. His high quality work has earned

00:04:23.020 him the trust of people like Ben Stiller, who he's operated on and who have spoken very publicly

00:04:28.200 about his own battle with prostate cancer. In this episode, we go through all of the current and basic

00:04:34.200 best practices for the screening and treatment of prostate cancer from the latest drugs to the

00:04:39.180 surgical options. The conversation naturally leads to our evolving understanding of cancer and the

00:04:44.380 most exciting areas of research in prostate cancer specifically. We also touch on the controversy

00:04:49.120 around the role of things like testosterone replacement in the development of prostate cancer

00:04:53.900 and even the controversy surrounding prostate screening using things like the PSA. And finally,

00:04:59.980 if you're an MD-PhD student, which I realize might not be many of you, you'll want to listen closely as

00:05:04.880 Ted has some of the most pertinent and, in my opinion, most important advice for those who are deciding on

00:05:10.000 how to thread this needle of being clinicians and scientists. So without further delay, please enjoy

00:05:16.980 my conversation with one of my closest friends from residency, Dr. Ted Schaefer.

00:05:23.780 Hey man, how are you?

00:05:25.120 I'm great. Good to see you.

00:05:26.240 Dude, it's kind of weird when I go and visit my friends from residency and I see them in their

00:05:30.820 grown-up clothes and their grown-up offices. It kind of makes me feel like I failed.

00:05:36.140 Well, your office is stunning. The view over the lake in Chicago, and admittedly, this might be

00:05:43.800 the best month of the year to be in Chicago, but it's like, we're in the elevator coming up here and

00:05:48.340 I'm, I feel like we're supposed to be goofing off like we always did. And then I'm like, wait,

00:05:52.240 we can't goof off. He's now the chairman of urology. We gotta, we gotta be serious.

00:05:56.820 It's true. When I, when I look at, I'm looking at you here doing this recording and I can't help

00:06:00.500 but just chuckle.

00:06:03.260 So we'll get to all the med school stuff or the residency stuff, cause that's obviously where

00:06:07.100 we met. But, um, let's talk a little bit about your decision to even do a PhD and, you know,

00:06:13.480 you have kind of an interesting story there cause you weren't on the typical MD PhD path, right?

00:06:17.920 Yeah. I, I, you know, people ask me about my life and how I got to where I am. And there's a couple

00:06:24.220 principles I think about and they're common themes that we share together. But one of the things I

00:06:29.340 teach or talk to my trainees about is, you know, you never walk by an open door without looking

00:06:35.460 inside. And so that's how I ended up being at the NIH doing my PhD. But even before that, I think the

00:06:43.120 way my brain was built was that I always wanted to see what was inside the open door, inside the

00:06:49.860 alarm clock, inside the watch. And so conceptually, as I moved through my, my training, I liked biology

00:06:58.700 cause I wanted to understand how things worked. I loved organic chemistry. I love putting the

00:07:02.620 puzzles together, making things happen. And so as an extension of that, when you're in medical school

00:07:09.040 and you're learning about the pathology of why things, you know, fail, understanding that at

00:07:13.660 the cellular level, just always appealed to me. And I loved the ICU. I loved the, you know, the

00:07:19.520 physiology of the human body and how you can measure all that. And so I, I think about that a lot.

00:07:25.220 Cause I, you know, read and been following your blogs and your life and how you analyze everything

00:07:29.000 you do. And so for me in medical school, it was a lunchtime thing. I went by this open door and

00:07:34.520 there was this opportunity to apply for a scholarship through Howard Hughes medical institution to really

00:07:40.040 go study science at the NIH. And I had started college and school early. So I had about a, I felt

00:07:46.800 like I had a year to kind of play around and see what was interesting to me. And it was something that

00:07:52.420 was out of the box for me, but I just, you know, when you find something that makes sense, it's no longer

00:07:57.720 risky to you. You're not exposing yourself to anything. It's really just exploration. And so that,

00:08:03.260 that came very natural. Cause I'm not the type of person who likes to take on risk, do different

00:08:09.120 things. But for me, it wasn't a risk to just leave medical school and go to the NIH. It was an

00:08:14.380 opportunity. When you were in college, did you know you wanted to go into medical school?

00:08:18.000 I think so. Yeah. I loved, I loved biology. I love understanding the way things were and how they

00:08:24.840 worked. And you know, the most complex of all those things is the human body and just a living

00:08:30.540 organism, a multicellular organism is just incredibly fascinating to me. So I was always attracted to

00:08:36.680 that. And so I thought, you know, that was a natural extension of it. I remember when I was in

00:08:41.360 college, there was a very famous anthropologist at university of Chicago, who was one of these

00:08:46.760 dinosaur hunters. And so I just, you know, I loved, I loved the idea of just discovery. And I love that

00:08:53.620 idea of anatomy and discovering what dinosaurs were like and how they did that. I remember I talked to

00:08:59.400 my father, who's a physician and I said, you know, I think I want to go off to grad school and be an

00:09:04.240 anthropologist. And he's like, you're going to do what? You know, but that concept of discovery,

00:09:10.200 innovation, figuring things out, it's just something that I've always had in me.

00:09:13.720 So you don't just go to NIH. How did you wind up in the lab of a Nobel laureate?

00:09:19.300 Well, it was through a friend of mine. So when this program I was in, you know, you went and you

00:09:24.920 interviewed in, in different labs and you basically decided what you wanted to do. And

00:09:30.100 some people, it was an incredibly talented group. It was about 40 medical students from

00:09:35.200 all over the country. So some of these people, they're just amazing. They knew what they wanted

00:09:40.640 to do. They knew what field, who they wanted to work with and so forth. I wasn't sure what

00:09:45.760 I wanted to do. I knew I wanted to pursue this idea of discovery and pursue it at a high

00:09:51.700 level. And I remember there's a guy named Jonathan Ashwell. He was an immunologist and

00:09:56.880 I thought, well, maybe I should do immunology mostly because I didn't really understand immunology

00:10:02.040 very well for my medical school class. It was a weak kind of class for me. So I went and

00:10:07.760 talked to him and he said, you know, he's a really tough guy, very successful, hardcore

00:10:11.300 scientist. And at the NIH, immunology there was just really, really, you know, just amazing.

00:10:16.760 And, um, he said, listen, you just got to pick a guy. He was really tough. He just said,

00:10:21.800 look, just can a man up, pick a, pick something and you'll get into it and you'll love it.

00:10:26.300 And I thought, you know, that, that was actually good advice, you know? And so I was shopping

00:10:31.600 around for somebody who was motivated, who was driven and who was smart to work with.

00:10:36.400 And a good friend of mine, who's actually here at Northwestern Grand Barish, you should look

00:10:40.560 at this, go talk to this woman, Pam Swartzberg. She's a postdoc in the Varmus lab and she's

00:10:45.600 looking for a student and she's really good. And so I went interviewed with her and she was exactly

00:10:51.920 what I wanted. I mean, she's a brilliant scientist and she happened to be in the Varmus lab, but,

00:10:57.680 you know, the Varmus lab was a bunch of postdocs who would be effectively associate or full professors

00:11:02.740 at any other university. They were just incredibly smart people. And I got to, you know, these,

00:11:07.680 these individuals are just amazing. So I, you know, met her and then, you know, worked through her

00:11:13.040 with him. And the plan was always to, she had already been offered a position as a researcher

00:11:18.560 at the NIH and she was waiting to transition to her own lab. So we, yes, technically I was a

00:11:24.980 Varmus lab member for six or nine months. And, but all along I was mentored by this woman, Pam

00:11:30.100 Swartzberg, who was just a brilliant scientist. And when she was a tech in her lab at Columbia,

00:11:35.660 she was making, you know, she was had covers of cell, you know, she was just brilliant. So

00:11:40.620 Harold attracted people like this in his lab group. And we stayed part of his lab group,

00:11:46.200 although independent throughout my kind of experience there. And I always considered our

00:11:51.620 group to be equal, but part of his group. So it was, it was a lot of fun to interact with him

00:11:56.060 on a weekly basis during lab meetings, just to see how he thought. I mean, you know, like you,

00:12:01.280 I like to surround myself with people who are just incredibly smart. And by being a member of

00:12:06.700 his lab team, I, by default did that, not just him, but many, many other people. So it was really

00:12:11.720 fun. For the listener, of course, Harold Varmus and Michael Bishop shared the Nobel prize, probably

00:12:16.120 in the late eighties or early nineties, it was like 88, 89, 90, something like that. Right. They

00:12:20.160 basically were the first people to elucidate the relationship between viruses and oncogenes. Is that

00:12:25.640 correct? Right. Yeah. So the concept of their, their prize was, and I'll probably butcher this and the,

00:12:30.760 the real scientists out there will kill me for it. But, you know, the idea was that they described

00:12:35.080 that there's this, you know, you could pass on a cancer through a viral induction. And so these

00:12:39.980 viral oncogenes was what they described. So they were an active alteration in the cell's normal

00:12:46.260 machinery to, to induce a cancer. You know, I've never met Harold, but I did have the privilege of

00:12:50.700 having dinner with Michael Bishop once a few years ago, and it was a very intimate, you know,

00:12:54.380 there's like four people there, but everyone was either a Nobel laureate or will be a Nobel

00:12:58.280 laureate sort of thing. You know, Lou Cantley, David Sabatini, Michael Bishop. And, you know,

00:13:02.640 it's just one of those nights, like you don't want it to end. You can't believe that, you know,

00:13:05.780 because we were at a steakhouse and we were sort of sequestered in our own little room. And we

00:13:09.600 probably spent like five hours there just talking about their work. It was amazing. You said something

00:13:14.220 a second ago that I love. I didn't know this about you actually. So this is the fun thing of

00:13:18.400 interviewing your best boys is you still learn something. Part of the reason you were attracted to

00:13:22.500 immunology is you felt it was a weakness. And having spoken with a number of very good

00:13:26.620 scientists, I find that to be a very common thread. The great ones seem to go towards their

00:13:31.700 weaknesses rather than away from them. Steve Rosenberg, who was my mentor at the NCI,

00:13:36.300 always talked about the reason he did. He always knew he wanted to be an immunologist,

00:13:39.860 always non-negotiable, but he did his PhD in biophysics because he didn't want to be intimidated

00:13:45.300 by these differential equations when he read papers. Like he really wanted to understand a field of

00:13:50.060 science that didn't come, you know, sort of easily to him. So that's sort of an interesting aside

00:13:55.340 about you. Yeah, it was funny. I had a great mentor and worked hard and, you know, on paper had a great

00:14:01.600 PhD. And I remember it was degree granted through the University of Chicago. So again, I wasn't in a

00:14:07.160 formal PhD program. There was an open door for me to do this great, you know, this great program and

00:14:12.400 opportunity at the NIH. I went there for a year. I just loved it. I loved the research environment.

00:14:17.360 And from there, I petitioned to stay an additional year. And I didn't really know what it meant to have a

00:14:22.560 PhD. I mean, I wasn't going there for a PhD. I was going there to do science. But I had friends that

00:14:27.520 were in formal MD-PhD programs at University of Chicago. And they were like, man, you know, what

00:14:33.060 you've done is PhD students would die for. And I was like, well, I don't know. I'm just doing my thing,

00:14:37.940 you know. So at that time, I was an idiot and I was kind of ballsy. So I wrote a letter to my dean

00:14:43.060 and I said, well, I think I should be, I should be, someone should give me a PhD for this stuff.

00:14:47.620 And they said, well, why don't you fly back and why don't you give us a talk? And I did. And they

00:14:52.100 were like, okay, yeah, you do know what you're talking about. And what you had published, you have

00:14:56.960 actually a very similar story to another good friend of mine who, you know, was in a similar situation

00:15:01.720 where he basically was in the right place at the right time, right? Was in a great lab, very well

00:15:06.560 mentored, great project, and was willing to like go to the wall for it and ends up getting a first

00:15:12.320 authorship in science and nature. And it's sort of like, you just have to hand those in and that

00:15:16.740 becomes a PhD. That's the idea, you know? And so yes, all the critical thinking and how to develop

00:15:22.000 and come up with on a hypothesis and test it. And I did all those things. So, I mean, I met all the

00:15:27.180 formal criteria for it. I just did it in a, I wasn't in a structured way. It just happened to be in a

00:15:33.060 good environment and work. What was the most interesting question you were asking during your

00:15:36.900 time at NIH? Well, I mean, I think immunology and really, I think I was more in a cell signaling lab.

00:15:44.380 And so a lot of what we did was biochemistry. And the idea was, you know, well, you would take a

00:15:51.340 single protein and you'd knock it out or turn it on or whatever, and it would have a huge effect.

00:15:56.960 And I think at that time, people were thinking really very linearly, you know? And I had, I mean,

00:16:02.660 my PhD was pretty much the most amazing experience you can imagine. So on my floor in building 49,

00:16:09.820 it was- This was in the old center.

00:16:11.020 This is before- Before the new mineral center was built, which was-

00:16:15.000 But building 49 was a genome institute. It was across the street from the NCI

00:16:18.880 buildings, which I think were 35 and 37 or something like that. So on my floor was Harold

00:16:25.160 Varmus, you know, Varmus lab. I was technically in our own lab with Pam, but we shared lab space with

00:16:31.760 Francis Collins. So, you know, it was just, I mean, you couldn't just pick a better floor to have

00:16:37.900 just people on. And so at that time, genomics and transcriptomics-

00:16:41.880 This is the mid-90s?

00:16:43.880 This is 97 to 99. So, I mean, people were just starting to do homemade microarrays and looking

00:16:49.860 at expression. And I remember people would like take a muscle cell and they compare it to a fibroblast

00:16:55.280 and they would be like, oh my God, you can see these different expression changes in these homemade

00:16:58.880 microarrays. And so that's when everything was just taking off. I remember Lou Stout, who's still at

00:17:04.320 the NIH, who was working on, there was a Howard Hughes student working on lymphomas and just

00:17:11.100 characterizing the different genomic phenotypes of them. And people still use that stuff today.

00:17:16.100 It's pretty amazing. And so I was there when all that was happening. I was, I remember when I went

00:17:21.680 there, you know, at University of Chicago, people really weren't on the internet. And then I show up

00:17:26.780 and I go to the lab and there's T1 lines at the NIH and the internet. And I remember downloading the

00:17:32.520 Clinton debacle, you know, and reading that in detail. And so like, there's all these just amazing

00:17:37.420 things that happened in science and happened in technology that were going on at that period of

00:17:42.480 my life. And that period in the world, it was pretty, it was pretty amazing. So, so the thing

00:17:46.880 that's a long answer to the concept that when I went there, I think people were still focused on

00:17:52.280 single gene, single change. They're still looking for the like, well, you have this mutation,

00:17:57.020 you get this cancer, this mutation, you have this phenotype. And you know, you know,

00:18:01.640 the human body is a polygenetic organism. And so. Yeah. At last count, if there's 20,000 human

00:18:06.840 genes, I believe there's something like 73, but I could be wrong. Let's just call it a hundred and

00:18:12.480 round up. There were about only a hundred disease states that result from single gene mutations.

00:18:17.400 Yeah. Out of 20,000 genes. Yeah. So, you know, that was the big thing,

00:18:21.360 the big transition in Francis Collins was really leading that where there were people hunting for

00:18:26.180 the gene for type two diabetes at the time I was there. And of course, now we understand it's a

00:18:30.260 complex equation. And so within immunology, when I was there, it was also a transition.

00:18:36.980 So it turns out that the tyrosine kinases that I worked on in my PhD are really involved in fine

00:18:43.420 tuning the T cell receptor signaling. They're really rheostats. They really fine tune the signal.

00:18:49.060 It's not off or on just like, you know, you have a mutation in X, Y, or Z off or on. And so I think

00:18:55.040 one of the big themes of what was evolving at the time I was there was this concept that

00:19:00.200 was a fine tuning. And I remember we would do immunology retreats in the road.

00:19:03.880 So another way to explain this, maybe for the listener, because of course I hear rheostat and

00:19:07.300 I think about rheostats because I'm an engineer. Digital is a signal it's on or off. That's right.

00:19:11.820 Zero or one. Analog is like the volume button on your radio. You can go from nothing to full blast,

00:19:18.760 but an infinite number of iterations in between. And that's what you mean by modulating the signal.

00:19:24.200 Right. And I think that that was a period of transition in science where maybe people always

00:19:30.180 thought that that happened, but people were developing the tools to begin to test that

00:19:35.380 and understand that. And you think about cancer immunology and the Rosenberg lab was a huge

00:19:40.880 player on campus when I was there, which was 10 years before you were there. And they were hunting

00:19:45.240 for single tumor antigens, right? But then they were realizing that it's a complicated thing.

00:19:51.380 And it's, um, there's multiple factors that come into the role in the play there. So for

00:19:56.100 me, that was maybe conceptually something people had always thought about, but the tools to explore

00:20:01.580 that, the tools to, to test that on multi-gene levels were kind of coming online in science

00:20:08.340 at that time. So it was a pretty fun time to do that.

00:20:11.300 Talk a little bit about a tyrosine kinase. I mean, these, these are so ubiquitous in biology

00:20:16.880 that, and they just come up over and over again. So, so explain to someone who doesn't

00:20:21.380 understand what that is, what it is and why it's relevant and how, and maybe where it shows up.

00:20:25.900 You have your DNA, everybody's born with it. It's in every single cell in your body,

00:20:31.240 but the skin cells in your body make a certain amount of melanin that make you darker than I am.

00:20:38.520 And so within, between different people, there's variability in what the individual

00:20:42.920 cells do with the DNA. And then within the human body, there's different cell types and they use

00:20:49.060 the DNA, the code differently. That code then is incredibly, it's modified, right? By exposure to

00:20:56.120 the environment. And that's the epigenetic change. And what results is a protein. And so once you have

00:21:01.820 a protein, that's really what kind of constitutes a lot of what's in our cells in our body, but they're

00:21:07.160 not inert. They're constantly changing. And so one of the ways that they change and one of the ways that

00:21:12.080 the signals change within an individual cell, how the cells communicate with each other, et cetera,

00:21:17.220 is by having kind of temporary modifications to those individual proteins. And so one of the ways

00:21:23.360 that happens is through this, these type, these kinases, and there's different pieces of the proteins

00:21:29.340 that can be modified. So one of them is a tyrosine kinase, but there are other types of kinases. And

00:21:34.140 these are temporary modifications that happen within a protein, within a cell to typically

00:21:40.960 transmit a more acute or change within the cell or between two cells and so forth.

00:21:47.540 And of course, these have become a very attractive target for drugs.

00:21:51.280 Yeah. So one of the, obviously the, the idea in cancer biology is to find alterations, to find

00:21:58.640 mutations, to find changes that you can quote unquote target to do precision oncology, precision

00:22:05.440 medicine. And so these are one of the ways that we're beginning to think about, you know, advancing

00:22:11.080 the kind of medicine in that, in that special way. Gleevec targets a tyrosine kinase, doesn't it?

00:22:16.520 It does. It targets a specifically altered fused gene. So it's not just a random tyrosine kinase.

00:22:23.200 It's a tyrosine kinase that's altered by specific mutation within a cancer. I mean, it was, that was

00:22:29.740 how it was originally described. And so, yes, it will, it will target those and have a specific

00:22:34.260 effect. And that was, you know, work done on the West coast in part by Charles Sawyers, who's now

00:22:38.720 at Memorial, who's, you know, an idol of mine, but he wasn't the only one involved in kind of

00:22:43.620 identifying this fused mutation. It's sort of one of those exceptions to this rule, right? Where

00:22:48.920 if you have that mutation, which basically is, if I recall, is only showing up in

00:22:53.180 CML and GI stromal tumors, correct? That's right.

00:22:55.940 Then you do have the one hit wonder. You do.

00:22:58.420 This drug is, at least in the CML, it seems curative. I don't recall if it was actually

00:23:02.620 curative in just GI stromal tumors or if it was just basically could render it a chronic disease.

00:23:08.360 For the GI stromal tumors, it's not my space, but yeah, it works, but it does, there is resistance

00:23:14.680 that develops, I think in both models now, but in general for the liquid tumors, it's much more

00:23:19.680 durable. And for the GI stromals, it does help to suppress the growth of those tumors. Some of them

00:23:25.020 do recur and come back. And that's, you know, the concepts of how we manage and we've converted,

00:23:30.060 you know, HIV AIDS to, from a lethal disease to a chronic condition, really, those basic principles

00:23:36.400 of multi-targeting of the particular cell. So like for cancer, a single agent like Levec

00:23:43.040 isn't going to work because the cells change and alter, but doing double or triple targeting will

00:23:48.720 be an effective long-term approach for those, just like we've learned from HIV management.

00:23:53.080 So I'm sure today, you know, you're now the chairman of urology. So you are in, you know,

00:23:58.120 you encounter lots of residents and medical students and if one of them came to you and said,

00:24:02.420 hey, Ted, or I guess they'd have to call you Dr. Schaefer, but you know, I'm really thinking about

00:24:05.920 doing a PhD and what advice would you give them to select a good lab? In other words, you describe

00:24:11.520 so much of your trajectory is the, is you're the beneficiary of having been exceptionally well

00:24:16.520 mentored. And you, you know, you've talked about Pam now and before, I know we've talked about just

00:24:21.080 when you have an amazing mentor, it's like everything works out. And yet there are countless

00:24:24.980 students who go into labs that just couldn't waste more time. They don't actually learn how to think

00:24:29.700 properly. They come out as dumb as they were when they went in and the field has not advanced.

00:24:34.760 So in as much as surrounding yourself by the right people is the best first step you can take,

00:24:40.440 what guidance would you give somebody to, you know, what questions should they be asking? What

00:24:44.760 things should they be looking for either positive or negative to help them think through that?

00:24:49.440 Well, I think you've had an opportunity to interact with brilliant scientists all along. And for me,

00:24:55.320 it's the brilliant scientists, it's brilliant clinicians, it's just brilliant people. So what

00:24:59.540 are the essence of those people? That's how I would think about it. And mentorship matters,

00:25:03.820 obviously brainpower matters, motivation matters. So, you know, why is it that some PhD students

00:25:09.760 are not successful? Sure, you can attribute some of it to mentorship, but I really think that

00:25:15.520 it has to do with motivation and drive. And that's such a critical part of it. So then you'd say,

00:25:22.160 well, why is somebody not motivated? Why aren't they driven? I mean, I guess some people are

00:25:26.760 biologically built that way. But I also think maybe, you know, if you wanted to be nicer about it,

00:25:32.380 you could say, well, maybe they just haven't found what they're passionate about. Because I think that

00:25:36.640 drive, passion, they come from the same part of your heart or your brain. And so I think part of

00:25:46.060 that is just that, you know, have they found the right area? Now there are still, having said that,

00:25:50.800 there are people that are just super passionate about something and they want to do it and they

00:25:54.460 just can't. You know, maybe they just need to kind of move along. But I think that in my experience in

00:25:59.740 grad school is that there are, usually you can, it's not that hard to identify grad students that

00:26:04.860 aren't successful. It's pretty easy to find out, well, they're missing a major one of those

00:26:09.320 components. So you head back to University of Chicago, you wrap up your last two years of

00:26:14.660 medical school, at which point you have to decide what you want to be when you grow up and you pick

00:26:18.400 urology. Yeah. So I went to University of Chicago undergrad. So I spent 11 years at University of

00:26:24.900 Chicago and the first four years were the toughest years of my life, for sure. The undergrad. I learned

00:26:31.760 only one skill set and that was how to use my brain, how to think, how to think critically. You

00:26:37.560 know, that's why we became, I think, friends instantly at Hopkins was that I feel like that's

00:26:42.620 how your brain is built too. And you've exemplified that throughout your whole career. So for me, I

00:26:47.200 went there, I learned how to think, I decided I wanted to pursue biology at a deep level and I wanted to

00:26:53.480 pursue human biology. So then I went to medical school. Now for me, I think one of the key

00:26:59.660 components of having an effective research career to date, I guess, would be that I had a clear

00:27:08.440 understanding of this idea of translation. So you can do science for science sake, but to me, to make

00:27:15.100 really big impacts, you have to be able to translate that to the human condition. So I did three years of

00:27:20.900 medical school before I left. So I went away after my third year and then I came back. So you already

00:27:26.320 had a year of clinical medicine under your belt. Yeah. And so for me, so that's also very unusual.

00:27:31.400 It's definitely different, but I encourage all students who are MD PhDs to do a clinical time

00:27:36.100 before they do their PhD. So that, that's, that might be the nugget of the podcast right there,

00:27:40.220 because I don't think I knew a single MSTP student who didn't go straight into their PhD

00:27:45.680 after the preclinical phase. Right. So for me, it was just so impactful to be, I guess,

00:27:52.360 if you say in hindsight, well, what was the distinguishing factor of the Varmus lab crew?

00:27:56.960 They were all MD PhDs. They had all done clinical. So they knew really key nuances that were important

00:28:03.900 questions to ask. And it doesn't, you don't have to be an MB to get that. You know, one of my good

00:28:08.060 friends is his PhD who developed a genomics company that we may talk about later. And he's a straight

00:28:14.820 PhD. He shouldn't know prostate cancer like he does, but he really gets the nuances of it. So

00:28:19.320 I did three years of my med school. I went to the NIH. I did pure science. I didn't think about

00:28:26.400 humans at all, thought about mice and signaling and mice and T cells and mice and so forth. But

00:28:32.460 in the back of my brain, I was always like, okay, how are we going to change? How are we going to

00:28:36.600 think about the human condition, human disease, breakdown and, you know, rebuilding all that.

00:28:41.480 So from my perspective, I had, I had a jump on, you know, the other straight PhDs in the group

00:28:46.160 because I had a, I had an idea. Now, why did I choose urology? Well, this goes back to just an

00:28:53.660 early childhood imprinting. So there's a couple of facts. Number one, my dad is an incredibly famous

00:29:00.160 urologist. My father was the chair of the department of urology at Northwestern for 25 years before I took

00:29:06.400 over the job. And he's an incredibly successful scientist, doesn't do cancer biology. And I didn't

00:29:14.600 really even know he was a urologist as a kid. I just knew him as my dad. But one of the backstories

00:29:19.700 was that when I was in seventh grade, eighth grade and beginning high school, we used to go visit my

00:29:25.920 dad's parents. They lived in Northern Indiana, which is about a hour and 20 minute drive from where we

00:29:31.140 were. And over that time, my grandfather got sick and I have these just vivid memories of

00:29:38.980 seeing him. And, and they're really snapshots in my brain. I recall weekly of just becoming sicker

00:29:46.420 and becoming more frail, becoming bed bound and then dying. And I never really asked what he died

00:29:52.500 of. And I don't think I was, I don't think I could have processed it, what it would have meant anyway,

00:29:56.280 if I had asked. But when I was in medical school and I was doing my PhD, I asked my parents what he

00:30:01.960 died of and he died of prostate cancer. So I was at the NIH. I was doing science. I had done some

00:30:09.960 clinical work. I realized what people in DC, not in science, but in politics were interested in.

00:30:16.840 They're interested in cancer biology and they were interested in prostate cancer. So I saw what other

00:30:23.260 people were interested in. And I had this very vivid memories of my, you know, that my father,

00:30:30.000 my grant, my grandfather having prostate cancer and dying from it. And I decided that that's what

00:30:34.060 I wanted to do. So when I came back to medical school, I knew already that I wanted to be,

00:30:39.480 to be a prostate cancer biologist and understand the disease. I also knew that I wanted to be a

00:30:47.720 surgeon. And so I didn't want to be a medical oncologist, although that appealed to me a lot.

00:30:51.600 And I'm always flattered when people think I'm a medical oncologist because those guys are smart.

00:30:55.980 They're smart. But I knew I wanted to do something. I love working with my hands. So for me,

00:31:00.520 the idea of being a surgeon scientist was just, it just made sense. I love the biology. I love,

00:31:07.500 but I still love the idea of not just conceptually deconstructing something and putting it back

00:31:12.120 together, but actually physically deconstructing something and putting it back together. So it was a

00:31:16.660 perfect fit for what I wanted to do.

00:31:18.160 For the listener to put some things in context. At the time that you and I began our residencies,

00:31:23.460 I don't really think there was any debate about what the best urology program was in the United

00:31:28.080 States. I think there was a good race for number two. There were lots of programs that would have

00:31:32.440 competed to be the second best urology program in the country, but Johns Hopkins was hands down

00:31:37.700 in a league of its own. And they only take two residents per year. So if there are 400 or 500

00:31:45.580 medical students graduating who want to go into urology, only two of them get to go to Hopkins and

00:31:51.620 you were one of them, which perhaps isn't surprising. Did you want to go to Hopkins for

00:31:55.980 reasons other than it was the best program? Was there something about the environment there that drew you

00:32:02.680 to it?

00:32:02.960 Yeah, it was a people. It's an amazing place that I think about, think about it all the time. So I interviewed

00:32:10.000 there and the chair of the department at the time was, is the godfather of my field. He made all the

00:32:15.980 contemporary modern discoveries in prostate cancer. And it was real simple. He looked me in the eyes and he

00:32:22.060 said, I looked at your CV. I know what you have the ability to do and I want to help you get there.

00:32:27.940 So Pat Walsh selected you in as much as you selected Hopkins.

00:32:31.340 I guess you could say that. Yeah. You know, it was a perfect fit because as we've talked about,

00:32:36.040 mentorship is just so much of everything. It's everything in life, really. If you're motivated

00:32:40.220 and you have drive, it's, you know, even if you're not motivated and you don't have drive,

00:32:43.460 you need a good mentor. So for me, I showed up for the interviews. I'd interviewed all over the

00:32:47.960 country. You know, there was places I could have gone that I could have made a good opportunity or

00:32:52.320 good experience for me to be trained. But when I showed up at Hopkins, I was like, okay, this is,

00:32:57.180 I got to go here. So, you know, I think it was a good fit. He was interested in having me train

00:33:01.600 with him and I was interested in training with him. So it was perfect.

00:33:04.680 Did he know your father? He must've, they must've, I mean, they're both chairmen.

00:33:07.580 Yeah. It's an interesting story. He, I met him at a, I met him at a, a function in, in the fall

00:33:13.840 before I started. So before I had interviewed and he was, I was at a function with my father. And so my

00:33:19.580 father introduced me to him and he said, well, you know, what, and what do you want to go into when you

00:33:24.560 finish your medical school? And I said, well, I'm actually interested in urology. He said,

00:33:27.800 really? And he said, well, where are you applying? And I said, well, I've applied to all the great

00:33:32.720 programs. So, and he said, well, did you apply to Hopkins? And I said, I sure did. And he said,

00:33:38.340 that's wonderful. And then I find out from my father that he grabbed my dad when I had walked

00:33:44.180 away. And he said, I just learned that Ted applied to our program. Did we give him an interview?

00:33:49.820 And so it made me feel good that, you know, I had gotten this interview at the best place in the

00:33:56.280 country without using my father's coattails to kind of get the job. And then I showed up and it

00:34:01.520 was just an amazing, I mean, Hopkins was an amazing place. I know, I know you have many fond memories of

00:34:06.740 the place and I'll never forget just the pursuit of excellence is something I think about all the

00:34:12.760 time. And that was really the epitome of Hopkins for me. It was the pursuit of excellence among

00:34:17.620 everybody there, to be honest with you. Even the chairs of the departments, they pursued

00:34:22.580 excellence and, but it trickled down, you know, it trickled down to the everyday employees, the,

00:34:27.840 the physical plant people, the people who clean the floor, they had a pursuit and a passion for

00:34:33.200 excellence that at the time that we were there was amazing.

00:34:36.840 I remember also being so struck by that when, you know, when I arrived, because of course we're each

00:34:44.200 thinking about it through the lens of what we're going to do. You're going there because of

00:34:47.320 urology. I'm going there because of general surgery. The neurosurgery guys were going there,

00:34:51.000 but we all had this common first year. We were all, I don't remember how many, there must've been

00:34:54.940 28 of us doing internships in general surgery. Six of us would go on to do that track. Two of you

00:35:01.280 would go on to do urology. There might've been three guys in ENT and ortho and neurosurgery,

00:35:06.560 et cetera. But within about a week, I was like, Oh my God, this is like the all-star game. Like

00:35:14.620 these three guys that, you know, and I still remember everybody's names. Like those three

00:35:18.360 guys that were our classmates who went on to be neurosurgeons were out of control. They were so

00:35:23.600 good. Yeah.

00:35:24.240 The ortho guys, you know, ortho guys get a reputation of being kind of the jokers.

00:35:28.420 These guys were fantastic. Yeah. You know, they were, everyone was just so exceptional. So yeah,

00:35:32.640 you're right. It's a, you pay a little bit of a price. You got to go to Baltimore.

00:35:36.740 Yeah. Let's call a spade a spade.

00:35:38.300 That's right. Although we both met our spouses there. So, and I had my kids there. So there are

00:35:42.540 some upsides to it, but the reality is that, you know, it's funny because Pat Walsh, my mentor there

00:35:46.540 always would talk about that. He would always say, well, it's negative selection. People come here

00:35:51.740 because they want to pursue excellence. They don't come here because there's a good nightlife.

00:35:56.180 They don't come here because of X, Y, or Z. They come here for that single reason. And that's,

00:36:00.260 that's a great point. I never really thought of it that way, but it's so obvious because I remember

00:36:04.480 being so sad about having to leave California to train there. Yeah. But at the same time realizing

00:36:11.120 and talking a lot about it with Steve Rosenberg that was like, who had done his MD and PhD at Hopkins

00:36:16.560 that, you know, you only get one opportunity to train at this. This is the phase of your life.

00:36:21.740 to do this. So go to the best place you can go that fits with how much you want to work.

00:36:28.160 Let's talk for a moment about Pat's work because I don't think it can be overstated. And I don't think,

00:36:33.860 I mean, in many ways, I think Pat Walsh was a very unique mentor to you specifically,

00:36:39.220 but in many ways, the field of urology today is different because of him. And I don't think,

00:36:45.980 and I've thought about this, knowing that we were going to talk today, I've spent the last couple of

00:36:49.180 weeks thinking about this. And I have a hard time coming up with people in the modern era that rival

00:36:55.780 him. John Cameron potentially being one with respect to pancreatic surgery. But I can't think

00:37:00.780 of someone in the last 30 years that has so fundamentally changed the course of one operation,

00:37:07.020 its impact on one disease as Pat. Now, am I missing an obvious example?

00:37:11.540 Well, within urology, I think, I think I can't think of anybody within urology. And the other

00:37:17.760 point is, I'm sure that there are brilliant, outstanding people that have changed an operation

00:37:23.140 in a way that alters the course of those individual patients. But one of the things I think about a lot

00:37:30.560 is that Walsh would always tell me, you know, you can't make important discoveries unless you work on

00:37:36.500 important problems. So prostate cancer is a, it's an important problem and it's an incredibly prevalent

00:37:42.100 problem. So yeah, there's probably some guy out there who came up with the best way to do a

00:37:47.740 knick-knack whatever surgery, but if it doesn't have a high impact, it probably is not noticed. So yeah,

00:37:52.880 I think that what he did in our field was, you know, really was never been done before and probably won't

00:37:59.600 be done again. And he did it for a problem that was incredibly important.

00:38:03.740 So let's talk about the state of prostate cancer surgery for men prior to Pat's work.

00:38:10.580 If a man had prostate cancer, we'd be back in the early 70s, even late 70s, right? What were the

00:38:17.520 treatment options for him? Well, at the time that Walsh was training, very few people with prostate

00:38:22.160 cancer had surgery. And that was because it was a potentially life-threatening operation. People

00:38:27.720 would die from extreme blood loss. People were incontinent. People were for sure

00:38:33.560 impotent. Let's stop there for a second because this is one of those things that I think if,

00:38:37.880 unless you've been in an operating room, it's hard to understand why the blood loss from prostate

00:38:42.060 cancer surgery could be so deadly. It's the same reason until you see a trauma where somebody is

00:38:47.580 shot through the pelvis, you can't understand how did that person die? People get shot in the chest and

00:38:52.300 they walk away sometimes if it's, you know, not through the heart or a pulmonary artery or vein.

00:38:57.040 And yet a cross-pelvis gunshot wound is often quite fatal. What is it about that anatomy that

00:39:03.400 makes it so deadly? It's the large number and variable distribution of veins in the pelvis in

00:39:09.940 general. And why is it the veins, not the arteries, Ted? I love that I get to do this with you. I mean,

00:39:17.220 you know, the, the vein is just the, the wall of a vein is as thick as a piece of paper. So

00:39:23.140 it's prone to tear and it's hard to repair it if you do tear it. And an artery is much thicker. It

00:39:30.100 has much more resiliency to it. And it has to do with the amount of flow going through both of them

00:39:34.820 and pressure. So, so yeah, there's a lot of veins in the prostate, in the pelvis. There's a lot of

00:39:39.760 veins around the prostate and the, the distribution, the exact location is incredibly variable. So

00:39:46.540 they're more like venous plexuses versus a actual vein that you can name. But if you get into the

00:39:52.300 inferior vena cava, man, you're in trouble too. There's no doubt about that. I've, that's happened

00:39:55.920 to me a couple of times. So point is that anytime you, you know, an artery is the real deal, but

00:40:00.700 it's just easier to control it. And oftentimes if you cut an artery, it'll go into spasm and it won't

00:40:05.620 even, it'll just stop bleeding on its own. And that's not true for veins. So for one, and then also

00:40:10.700 there's the, there's the depth, right? There's the actual exposure is really tough in the pelvis.

00:40:15.380 You know, it's, it's one thing to, you know, look at the kidney where even though it's in

00:40:19.800 the retroperitoneum, you, you can be staring it straight in the face without too much work.

00:40:23.820 That's not really the case in the prostate.

00:40:25.740 Yeah. So, I mean, the way that Dr. Walsh describes it is that, you know, and people had done anatomic

00:40:31.140 studies for many, many years, right? I mean, for, for decades before surgery for the prostate kind of

00:40:36.400 was attempted to be performed. But the anatomy, when you fix a body and you study it,

00:40:43.120 it really compresses a lot of these sinuses. And so you don't really fully appreciate where they are

00:40:47.940 and what's happening and so forth. Anatomically, an artery is preserved, but these kinds of venous

00:40:53.580 plexuses were not. So the anatomy of the pelvis was not appreciated. But I will say that in 1904 at

00:41:00.120 Johns Hopkins, the first radical prostatectomy for cancer was performed by the chair there at the time.

00:41:06.800 And he did it through a perineal approach, which is the space between your scrotum and your anus,

00:41:12.020 basically. And when you do it, the surgery that way, you avoid... And the reason is that's the

00:41:17.340 closest place that the prostate gland is to the outside world. That's right. And if you do it that

00:41:22.540 way, you avoid a lot of the veins that bleed just, you know, catastrophically when you approach the

00:41:29.340 prostate from kind of above versus from below. And so that operation had been, was in, you know,

00:41:35.740 was being performed and it was considered to be, you know, was definitely safe. I mean, this life

00:41:40.980 threatening blood loss did not occur. And the problem was it wasn't a very good cancer operation.

00:41:45.560 Why is that?

00:41:46.080 Well, it had to do with exposure. Number one, I mean, you're doing, you know, the prostate is very deep in

00:41:51.140 the pelvis. So for the lay people, the way I explain, well, where's the prostate? I explain to people

00:41:55.780 that the pelvis is like a ring of bone and off the ring hang a bunch of muscles and that those

00:42:01.380 muscles form a hammock. At the bottom of the hammock is the prostate. And so it penetrates

00:42:07.280 through the muscles. And then that's where the urethra, the tube that you urinate through

00:42:11.780 comes through the pelvic floor muscles and then goes out of the body. So it's deep in the pelvis.

00:42:16.700 It's hard to access. It's hard to access from the perineum and it's hard to see what you're doing.

00:42:22.320 And it's harder to kind of excise tissue widely in that area. The exposure is tough when you do it

00:42:27.180 from above, but it's even tougher from below. So the life threatening bleeding wasn't there. But part

00:42:32.940 of the reason that the bleeding didn't occur when you did a perineal approach was because they were

00:42:37.040 leaving part of the prostate kind of in place. They were staying away from the area where the big

00:42:40.620 veins were. And so when you do that, it would be safer for the patient, but less oncologically sound.

00:42:46.480 So, and I can't believe I'm blanking on the forefathers, obviously Halstead, Osler,

00:42:50.540 Kelly, who was the, and Kelly was the gynecologist, obviously Osler, the internist, Halstead, the

00:42:56.560 surgeon. What was the name of the urologist? The first urologist at Hopkins was one of Halstead's

00:43:02.140 trainees. That was Hugh Hampton Young. So Hugh Hampton Young was a Halstead trainee. And so

00:43:07.600 people probably don't realize, but many subspecialties of medicine came out of the

00:43:12.740 Halsteadian era at Hopkins. And so orthopedics, radiology, urology, these were all subspecialties

00:43:21.620 that basically were Halstead telling Hugh Hampton Young, I think we should start a, you know,

00:43:27.240 an institute or a program for people with urologic problems. Now Kelly was doing some of that also

00:43:33.180 at Hopkins, just more on the female side. But, but that, that concept came out of Halstead really

00:43:38.860 assigning Hugh Hampton Young to do that. And the story is that he, you know, literally bumped into

00:43:44.060 him in the hallway and told him, you're going to go work on this. And he didn't really, he didn't

00:43:47.680 really want to do it because at the time it wasn't very sexy, but he did. And, and so from there he

00:43:52.800 really began the whole specialty of urology. Yeah. That's sort of the other thing about Hopkins

00:43:57.240 that never got old actually was to walk through Blalock and look at the photos of all of these old

00:44:03.220 photos of people who literally created the field of surgery. You know, the lineage there was,

00:44:08.920 was sort of staggering. Yeah. I think one of the things that you, I certainly didn't appreciate

00:44:14.120 was to really take it all in at the time. You know, I mean, I had the pleasure of being a

00:44:18.580 It's hard to, when you're sleeping, you know, I think an average of 28 hours a week or where we slept.

00:44:24.520 Right. Exactly. But you know, the idea of what we did was pretty amazing. I mean, remember we had

00:44:29.900 Sunday school, right? Yeah. Oh, I loved Sunday school. You know, we would show up. Can you explain

00:44:33.520 to the listener what Sunday school is? You and I might've been two of the, there weren't many people

00:44:37.400 that probably loved Sunday school, but you and I adored it. It was great. So when, you know, when

00:44:41.140 we were interns at Hopkins, there was no work hour limit. And you know, the expectation when you got

00:44:46.720 there was that you'd work seven days a week. You would work eight days a week if they're eight days in

00:44:50.460 the week. And so Sundays was the day that you would go in and you'd sit with the chair of the

00:44:55.240 department, one of the most famous surgeons of all time, really. And he would lead the discussion

00:45:02.260 on a topic for the day. It often started with history, right? We would do history of surgery,

00:45:07.980 history of surgery at Hopkins. And that was, those are some of my most favorite kind of discussions

00:45:13.720 was him just talking for 45 minutes about somebody. And then we would present cases and then we would

00:45:20.000 talk, we would practice our suturing. I remember we, I remember, I think Julianne Sosa,

00:45:24.740 who's the chair at UCSF now was taught me how to tie a square knot, you know what I mean?

00:45:30.060 So, and also once a year, we each took a turn presenting something back to the group. I still

00:45:35.000 remember what I presented on. I presented on the Warren shunt, which was an operation that I never

00:45:40.200 got to see because even by the time we were residents, interventional radiology had completely

00:45:44.940 nullified the need for that operation. But as a medical student, I became obsessed with the history

00:45:50.960 of that operation because of how dangerous it was and how complicated it was. This was an operation

00:45:54.880 for the folks who maybe don't spend a lot of time on the at Warren shunt Twitter handle.

00:46:01.720 There's probably no such thing. I hope someone creates one after this. It's an operation that

00:46:06.740 was done for people with elevated pressures in the liver. And this is something that happens when

00:46:10.840 people get cirrhosis. So this was basically an operation that would alleviate that by creating a

00:46:15.200 shunt in the liver. But I still remember that. And I remember like typing it up. And this was back in

00:46:20.800 the day when I would cut pictures out of textbooks and tape them on and make photocopies. And it was

00:46:25.920 awesome. This was old school. Yeah. So that was eight to 10 every Sunday morning, right? Yeah. And so

00:46:30.920 those kinds of things, I wish I could just, you know, people say, I wish I could go back to high

00:46:35.080 school. I wish I could go back to college. In many ways, I mean, I'd do internship all over again.

00:46:40.840 I would. I mean, we were there at what, 130, 236 hours a week. But man, I would do it all over again.

00:46:47.880 It was awesome. We did have amazing times. And I feel fortunate. I mean, there was just a great

00:46:53.260 group of people we met. You and I met immediately on day one. And then worked together. We were

00:46:58.440 together September. September of our intern year, we did pediatric surgery together. And Karen Kling

00:47:03.900 was our fellow. She is now an attending in San Diego. I bumped into her in the grocery store like a

00:47:09.840 year ago. She was great. She was amazing. Incredible. Yeah. She was awesome. John Vogel

00:47:13.500 was our... John Vogel was our senior resident. Senior resident. Taught me how to put an NG tube in

00:47:18.060 that served me. A nasogastric tube for the listener is a tube that you sometimes have to put in a

00:47:23.940 patient's nose down behind the pharynx and then into the esophagus and into the stomach. This is

00:47:29.140 something that is so ubiquitous in surgical care, but so wildly uncomfortable for a patient because the

00:47:34.660 patient is usually wide awake when you're doing this. And I remember one day Vogel, I remember where we

00:47:39.440 were. It was just at the ground level of CMC. He sat us down there in the playground and said,

00:47:44.960 look, you two knuckleheads, you have got to learn how to put an NG tube in without killing somebody.

00:47:50.160 And he didn't mean literally killing, but he just meant tormenting. And do you remember the Vogel

00:47:54.440 technique? I do still. Yeah. I remember him telling me. It was like, because everybody thinks that

00:47:59.160 you're supposed to put the NG tube up the nose, right? And he's like, it's straight back.

00:48:03.980 That's exactly right. And so he's like, you get the cup of ice, you get the ice water cup,

00:48:08.460 you put the NG tube in, you put a wicked bend on it, you put the lidocaine jelly in,

00:48:13.460 and that's exactly the key point. Do not go up, go directly back. And you curl it down. And then

00:48:18.980 you give them a little straw and you tell them exactly once you hit the back of the oral pharynx,

00:48:24.540 take two big sips. And this was a game changer, Ted.

00:48:30.100 It was. For the rest of my residency, I was throwing NG tubes. And if you looked at me,

00:48:34.360 you got an NG tube and it didn't hurt. The thing that the listener will not appreciate is the layer

00:48:40.840 of comedy associated with this, because this was done in what you described as the first floor of

00:48:45.720 the pediatric hospital, which was called the zoo, right? Yeah. And so this is a brilliant surgeon,

00:48:51.480 John Vogel. He's the head of colorectal surgery in Colorado, teaching Peter Attia, brilliant surgeon,

00:48:59.340 Ted Schaefer, just getting by in front of life-size stuffed animals of like giraffes and lions. It was

00:49:06.780 hysterical, right? It was just comedy. Yeah. That entire, that might've been certainly the best

00:49:12.340 month of my internship. Yeah. That was fun in terms of- I had great, many great months. Yeah,

00:49:16.520 pure jokes. So let's go back to Pat. I got us a little off topic. I actually, I got us way off

00:49:21.360 topic because we were talking about the bleeding, but there was this other enormous complication

00:49:24.700 of a prostatectomy, which was it virtually guaranteed that a man would not be continent

00:49:30.720 with respect to urine and would not be able to regain erectile function. And so I'm guessing that

00:49:37.200 many men when faced with an operation that's going to leave them in a diaper, unable to have an erection

00:49:42.660 might opt for not having surgery. Yeah. So people had radiation and radiation has changed a lot too.

00:49:50.200 So it was bad radiation or a bad surgery effectively. But you know, when you can actually

00:49:55.440 see what you're doing, just for the listener, putting, doing something when it's pitch blackout

00:50:00.060 versus daylight makes all the difference in the world. And so you, you know, you would go into

00:50:04.640 the operating room with him and he had just a mastery and he could control. He understood where the veins

00:50:10.440 were. He controlled them by suturing them before they started bleeding. And by doing that,

00:50:15.840 you could actually see everything. And once you could see everything, it was like obvious. You'd be

00:50:20.220 like, hello, why aren't people doing this or that? Now, the ability to maintain potency and

00:50:26.560 preserve, you know, sexual function was something that it's not so obvious how to do that. But he figured

00:50:33.000 that out by working with some anatomists and really just studying and talking to his patients and

00:50:39.000 listening to what they had to say. He also recorded all of his cases, which I do now too.

00:50:44.660 And I studied them and he learned how to kind of... I didn't know that about Pat. He would record all

00:50:51.040 the operations and study them. And I didn't realize that you were doing that either. I do now. It's

00:50:54.980 much easier now for us. I mean, we just hit the button, but every single case I record it.

00:50:59.460 And, you know, we're working on, I'm working on with one of my residents, just

00:51:02.240 making a photo video library. So what was hard for him and he's published and he put out on DVD,

00:51:10.060 you know, his operation, you can see it on YouTube and it's a brilliant thing.

00:51:13.800 But one of the things that makes doing any surgery fun is that there's so much variability in anatomy.

00:51:20.660 So what I'm working on now is a video library. So 10 bladder necks, 15 of these, because there's so

00:51:26.880 much variability in how the tissues present themselves to you. And then how do you handle that? And

00:51:32.080 that's part of what take, you know, surgical skill and hours in the cockpit do for you. So

00:51:37.200 we're doing with one of our lab residents this year, we're just taking all these videos. And so

00:51:41.980 whenever I do a case and the anatomy was really nice for X, Y, or Z, I'll tell them, yeah, pull that

00:51:47.920 case. And it's in the third 20 minute clip and pull it and make a short, you know, just make a clip

00:51:52.360 of that for particular steps of the procedure. Was there a moment when Pat realized he was onto

00:51:58.220 something and that this was, we were basically witnessing a paradigm shift, which is such an

00:52:03.060 overused term, except here it's not at all. It's actually an understatement here, but such a paradigm

00:52:07.340 shift in how an operation was going to be done. I mean, this would have been in the early 80s,

00:52:10.280 I'm guessing. It was, yeah. Well, mid to late 80s or late 80s, early 90s. And so it was, I think

00:52:16.840 he knew all along he was onto something and he was very confident, you know, he's not a shy guy and

00:52:22.400 he'll tell you that. So he was incredibly confident that he was onto something and that what he was

00:52:27.200 doing was the right thing to do and was very convinced of that and was convincing of that

00:52:32.440 when he spoke about it publicly. I think that the general community was less convinced that that was

00:52:38.220 what he had done was really happening. But I mean, I saw it, you know, I mean, I was really training

00:52:44.420 there at the heyday, the peak of Brady urology, Johns Hopkins urology. And so I got to see it in real

00:52:51.020 life. And, you know, I never saw bad surgery. That's the thing. I mean, you know, we trained

00:52:55.480 at this place and you didn't really, rarely did you see people do a bad operation. So

00:52:59.460 part of learning is to see the good stuff and the bad stuff and put it all into perspective.

00:53:02.980 And we didn't have most of the time that didn't happen there. So I saw it and I think he was

00:53:07.180 convinced of it from the get-go. So you're saying it just kind of took a little bit of time for the

00:53:10.640 data to speak for itself. I mean, the results. So if a patient today goes to a highly trained or

00:53:17.680 competent urologist and is going to have a prostatectomy and this, it's a 60-year-old man,

00:53:24.420 what can you guesstimate about his probability of regaining sexual function?

00:53:29.640 It's not 100%. And it's not 100% because-

00:53:33.180 It used to be zero, but now it's-

00:53:35.760 Well, you know, the nerves that we preserve at the time of surgery to optimize recovery of

00:53:40.780 sexual function are not myelinated. So they're incredibly sensitive to any kind of manipulation,

00:53:45.420 any kind of trauma. So, you know, one of my good friends is a hand surgeon and he does

00:53:49.920 microvascular nerve grafts all the time and the nerves regenerate and regain function.

00:53:55.200 They do that because they're myelinated and they're incredibly protected.

00:53:58.800 I didn't realize there were such thing as non-myelinated nerves.

00:54:02.280 Are there other places in the body where these exist besides the prostate?

00:54:05.340 I'm sure there are. I just, I'm a below the belt guy. So I don't know.

00:54:10.020 Is there an evolutionary reason that those would not be myelinated?

00:54:13.440 I don't know, but we can, I'll call Pat Walsh up when we finish this and he'll tell me for 20

00:54:17.300 minutes what an idiot I am and how I didn't know that. And so-

00:54:19.840 Can we record that discussion?

00:54:22.720 We probably could.

00:54:23.660 Okay. So that's a very interesting point that I actually was unaware of. And I can see now why

00:54:27.660 that makes it that much more difficult.

00:54:29.440 Right. Because you can preserve this tissue and you can do it in a way that's minimally traumatic

00:54:35.860 for the tissue. Yet it's not a guarantee that there'll be a hundred percent recovery of function

00:54:41.660 or any function recovery. Right. And so that is the variable. And that's the fact that it still

00:54:47.320 hasn't changed. You know, like Dr. Walsh would always tell me if, if we could do the perfect

00:54:51.880 operation, there'd be no dispute about doing prostate cancer surgery, perfect operation,

00:54:56.900 100% cancer control and no side effects. So I think in this day and age, you can be nearly

00:55:04.360 perfect for kind of urinary control. You're never going to be perfect. So when people say that none

00:55:08.980 of their patients have urinary leakage, it doesn't make any sense because if you actually survey 60

00:55:14.840 or 165 year old guys, 4% of them will have urinary leakage. I mean, so incontinence is something

00:55:21.740 that happens. It's much more common in women, particularly aging women, but it's also occurs

00:55:27.720 in aging men. So to say, well, I do a hundred percent of my cases and there's no urinary incontinence,

00:55:33.480 that's kind of means it's better than the baseline. So it's hard to believe. Yeah. But you can get

00:55:37.840 people up to very, very close to that number. So I always tell people for me personally, 98% of my

00:55:43.440 patients are totally dry where one small pattern line or day, which often people just wear for

00:55:48.700 protection when they're out and about. Functionally, totally fine. Now for a 50 year old man, I think

00:55:55.320 there's a over 90% chance that you can recover. Sexual function. Yeah. But with each deck member,

00:56:03.200 you know, erectile dysfunction is a disease of the aging male. So for each decade that somebody gets

00:56:08.080 older, there's a decline in sexual function. So even if people say that they're totally potent and

00:56:13.640 they're 70, they'll tell you if you ask them, oh my, yeah, I'm not as good as I was when I was 20.

00:56:18.380 So there's that component of things. And the other factor is prostate cancer. And it's not like

00:56:24.440 there's the prostate, there's five millimeters of tissue, and then there's this nerve bundle.

00:56:30.400 There's the prostate, there's no capsule or lining encasing the prostate. And then there's the

00:56:37.780 neurovascular bundle of Walsh named after Dr. Walsh. So you have prostate, the prostate itself has

00:56:45.400 different zones or different regions. Prostate cancers develop in the peripheral region or

00:56:49.900 peripheral zone. So right at the edge of the prostate. So you have a tumor at the edge of the

00:56:55.260 prostate, and then you have the nerve bundle. And so you're talking about one or two.

00:56:59.900 So that's kind of a cruel trick of fate is to have the cancers not develop centrally.

00:57:04.540 They don't develop centrally. They develop peripherally. So I understand why patients by

00:57:10.380 listeners just say, well, why don't you just, you know, well, I don't get it. Because in many cases

00:57:15.100 today, I've published on this a lot now, you know, there's prostate cancers that we pick up today are

00:57:20.580 just bulkier, they're more aggressive. And so when you have a tumor that you know is going to be

00:57:25.660 outside the prostate, you know, it's extra prostatic. It's involving the nerve bundle a lot of the times.

00:57:31.420 And so you have to remove part of it. You have to remove, you know, the tissue around it to try to

00:57:35.900 clear your margins. And so when you do that in a 65 year old guy, and you take out half of his nerve

00:57:41.520 on one side, it's unlikely that he'll be able to regain sexual function on his own. Now these days,

00:57:47.860 I try to be very upfront about that. And I try to set appropriate expectations. We can we have special

00:57:54.200 tools that we have in neurology that will enable a man to get total satisfaction sexually. So we can

00:58:00.560 maneuver around that, so to speak. And these days, many of the people I see have very aggressive

00:58:07.260 cancers that are, quote unquote, the real deal. So we really have to be careful. And, you know,

00:58:12.380 our number one goal for doing cancer surgery is to get the tumor out. Let's talk a little bit about

00:58:16.220 prostate cancer, because it's not a cancer that comes without its controversy. So let's start with

00:58:21.560 the biggest controversy, or certainly one of the biggest controversies, or things that would confuse

00:58:25.200 the lay person. Because about every year, the advice changes on this thing called PSA. So what is

00:58:33.380 the prostate specific antigen? PSA is a protein, it's made by the prostate, and its normal function

00:58:40.880 is to liquefy semen. So it's highly expressed in the prostate. So the way I explain the prostate to

00:58:47.440 people, it's the best analogy I can come up with is if you think about it like a sewer system, you have

00:58:53.800 the main sewer leaving the city. That's the urethra, that's the tube that we normally urinate

00:58:58.960 through. But this channel also delivers semen out the tip of the penis. Off this main sewer are

00:59:05.660 slightly smaller sewers that go to different neighborhoods. Within the neighborhood, there's

00:59:10.420 a sewer that comes out of the individual house. And the individual houses in this analogy are prostate

00:59:15.720 epithelial cells. They make components of the semen. And the semen is used to give nutrients to the

00:59:23.540 sperm while it's trying to fertilize an egg to enable the sperm to penetrate the cervical mucus,

00:59:30.380 these different functions. PSA is a protein that breaks down the semen and liquefies it.

00:59:35.740 And people think it's important for this whole process of fertilizing an egg. So that's what it

00:59:41.920 does. And if you look in the semen, the PSA numbers are 100 million per ml. I mean, the numbers,

00:59:49.060 the amount of this protein in the semen is astronomically high. So that's what it is.

00:59:55.980 That's what it does. So how do we use it as a tool to screen for prostate cancer? Well, we check the

01:00:01.680 values of the PSA in the blood. So since the prostate is a sexual gland, if you check the values

01:00:08.380 of a PSA in an eight-year-old boy, it would be zero because there's no testosterone in that boy,

01:00:14.760 there's no sexual development in that boy. And therefore, there's, you know, I mean, there's some,

01:00:20.020 but effectively, no. Before puberty, there's very little levels of testosterone. There's no

01:00:25.200 effectively prostate epithelium, and there's no PSA. As a boy goes through puberty to become a young

01:00:31.720 man, and then as he goes through the aging process, his prostate develops. And then it starts to produce

01:00:39.200 PSA as part of the components of the semen. Now, there is a certain amount of leakage of the PSA fluid

01:00:47.260 into the bloodstream. It's not, quote unquote, supposed to leak into the bloodstream, but it can.

01:00:53.220 And as the prostate gets bigger, so think about this concept of this underground sewer system,

01:00:58.620 the New York City sewers, right? They're getting older, they're getting leakier. And the bigger the

01:01:04.180 prostate gets, and the prostate gets larger as we get older, some of these pipes get leaky, and some

01:01:09.960 of the PSA leaks into the blood. So it was discovered in the 80s that there's this prostate-specific

01:01:17.260 protein that you can pick up in the semen, and you can also see in the blood. And so it is not

01:01:24.780 cancer-specific. It's prostate-specific. And it's actually a very good biomarker for prostate size.

01:01:32.340 The bigger the prostate, the more leaky it is, so to speak. And the leakier it is, the higher the

01:01:38.100 numbers can go in the bloodstream. So there's two variables that can progress over time. The size

01:01:43.800 itself, which you could talk about that independent of size. So two 30-year-olds, one guy's got a five-gram

01:01:50.460 prostate, the other guy's got a 100-gram prostate, just to make it extreme. You should see a difference.

01:01:55.120 But also, two guys with the same size prostate that are two decades apart, you might see a higher PSA

01:02:00.740 in the older fellow. That's right.

01:02:02.680 And if you do, for example, like we were always taught in residency, even though I wasn't a

01:02:08.200 urologist, you still once in a while have to, we still did a urology rotation. If I recall,

01:02:12.400 you wouldn't check a PSA on a man right after doing a rectal exam on him. Because in theory,

01:02:17.020 that could artificially have raised the PSA, presumably by creating more of an insult and

01:02:21.520 increasing that flow.

01:02:22.740 Pushing some of it into the bloodstream. So what can make the PSA rise besides just getting older

01:02:29.780 and having a larger prostate? Well, if you get an infection in your prostate. So think about that

01:02:35.720 like you got your city, you have your sewer network, and there's an earthquake. All the pipes are rattled

01:02:40.900 a little bit, and they all are extra leaky. And that's what an infection is. It's not infections in

01:02:46.640 the prostate are either all or none, really. They're not focal. So the whole prostate gets

01:02:50.940 more leaky and the PSA number can go way up. The other way to think about it is if you have a cancer

01:02:55.420 and the analogy would be, well, there's a city block that has the pipes, you know, the sewer

01:03:01.240 systems clogged. There's more backflow into the bloodstream, and that's how you pick it up. That's

01:03:06.140 not really how it happens, but that's a good way for patients to think about it. So what is a normal

01:03:11.200 PSA? Well, a normal PSA is age-adjusted. So a normal PSA for a 40-year-old is around 0.5 to 0.6

01:03:19.980 nanograms per ml. For a 50-year-old, normal meaning this is the median for all the population. For a

01:03:26.300 50-year-old, it's one. And so it kind of goes up stepwise by decade. So there are age adjustments

01:03:32.680 that we do for the PSA number. Now, what are PSA numbers that tell you you don't have a cancer?

01:03:38.500 There's no PSA number that is 100% no cancer. But there is a proportional rise in cancer detection

01:03:47.120 with rising PSA numbers. So originally, the cutoff was set at a PSA of 4. We do, you know,

01:03:55.460 we think about things more based on the individual scenarios. So if you're a younger person, if your

01:04:00.800 PSA is more than 2.5, that's usually considered to be abnormal and you may need further workup.

01:04:07.200 You don't need a biopsy right away these days, in my opinion, but you need further workup.

01:04:10.800 So it depends on the age of the patient and depends on how also their prostate size.

01:04:15.520 Now, many guys will go and when they get their PSA checked, there's another thing that gets

01:04:19.840 checked called the free PSA. And then a number is reported, which is the percentage free, which

01:04:24.880 is obviously that, you know, if their PSA is 3 and their free PSA is 1, then the percent

01:04:29.880 free is reported as 33%. What does that mean?

01:04:32.500 These are different ways for urologists to try to fine tune this prostate specific antigen

01:04:39.920 test to make it more a cancer specific test. So again, PSA just goes up when you have, and

01:04:46.960 every man has, it's not cancer specific. So percent free PSA was the first way that urologists

01:04:53.840 began to look at, well, what's the chance that a PSA of 4 is coming from a cancer versus a PSA

01:05:02.220 4 coming from just benign overgrowth. So remember, there's a lot of factors in play. One would

01:05:07.100 be if you had a man whose prostate volume was 80 grams, that's big, and his PSA was 4, well,

01:05:14.420 that's a low ratio. That's something called PSA density, how much PSA is made per gram of

01:05:19.840 tissue. So you'd say, well, that guy, it's very low chance that he has a cancer. That guy

01:05:27.700 would also have a high percent free PSA. So percent free PSA is another way to just look

01:05:34.880 at, well, how much of the PSA is produced from benign cells versus cancerous cells.

01:05:39.580 So if two guys have a PSA of 4 and one has a free of 1, so he's 25% free, and the other

01:05:46.480 guy has a free of 3, which is 75% free, what's the different physiologically in those situations?

01:05:52.340 Well, there's less bound PSA in the lower percent free, and that's more often associated with

01:05:59.220 prostate cancer. So that's just a correlation. So it's not like it means that-

01:06:03.920 In other words, we can't infer what, because I would have assumed that the binding protein

01:06:08.340 is in the periphery. It's in the plasma, right?

01:06:11.400 Yeah, it's bound up when it comes out of the epithelial cell. So it's just how it's processed.

01:06:17.020 So PSA's process is not a full-length protein when it's born. And so the other way that we

01:06:23.240 now, so just for the listeners, so we have absolute cutoffs for PSA for an older man,

01:06:28.960 2.5 and younger man, but they're all really case-specific in my opinion. Percent free PSA

01:06:34.160 was the first way to say, let's try to fine-tune what the PSA means. So a high percent free PSA

01:06:40.300 is associated with a big prostate, less of a chance of prostate cancer. A low percent free PSA

01:06:46.220 is associated with a higher likelihood that that PSA is produced from a gland with prostate cancer

01:06:53.880 in it. The other variables that we use are PSA density. So that's highly predictive of what's

01:07:00.640 going on in the prostate. So an easy threshold or cutoff for you, Peter, we talk on the phone

01:07:06.140 about some of your patients. Percent free PSA density more than 0.1, it raises a little bit

01:07:12.380 of a red flag. A PSA density of more than 0.15, that raises a red flag. So think about it. And

01:07:18.760 that median prostate volume for a 60-year-old guy is 40 grams. So 40 gram prostate, PSA less than 4,

01:07:28.100 it's probably, it's pretty safe. A PSA of 6, that raises red flags. And you know this from your own

01:07:34.920 patients that, okay, that guy probably has something going on. So that's how I think about it. Now think

01:07:40.500 about the 80 gram prostate with the PSA of 4. Oh, you have these patients in your practice. They

01:07:46.040 don't have cancer on average, right? A percent free PSA helps with that. There are two other new tests

01:07:52.220 that... Yeah. So you got me onto the 4K two years ago, and I really consider it a game changer for the

01:08:00.600 guys like me who were in the peanut gallery. So I don't, you know, I make it my job to know as much

01:08:05.740 as is knowable with the time that I have about every possible disease that could afflict my

01:08:11.180 patients. But that means I need to spend as much time thinking about colon cancer as I do coronary

01:08:15.840 artery disease, as I do prostate cancer. So for me, the 4K, which again, you didn't, I mean, you did

01:08:22.800 me a great service. Not only did you get me interested in, but you introduced me to Andrew at Memorial Sloan

01:08:26.560 Kettering. I'm blanking on Andrew's last name. Andrew Vickers. Vickers. Yeah. Amazing guy. Yes. And I mean,

01:08:31.800 the guy couldn't have been more generous with his time. I mean, he just gave me the schooling

01:08:36.020 tutorial on this topic. So good. You know, we put together a patient handout on this thing and he

01:08:40.900 even edited it for us. I feel like not an, I'm worried not enough patients understand that. And

01:08:47.740 I'm worried not enough primary care physicians understand the importance of the 4K test. Can you

01:08:51.780 explain how that has changed the way we do things? So this test you're alluding to, and there's

01:08:57.280 another test that performs equally well called the Prostate Health Index or PHI test. These both

01:09:03.020 leverage off this idea that prostate cancer cells make PSA differently than benign prostate cells.

01:09:12.580 And so the 4K score is the four calocrine tests. It takes PSA, percent free PSA, intact PSA,

01:09:20.500 and HK2. It takes those four prostate specific proteins produced. And it has a calculator to

01:09:28.540 really just discriminate between a cancerous cell and a benign cell. PHI uses the similar concept.

01:09:36.760 It uses something called minus two pro PSA, which is PSA for all the scientists out there,

01:09:42.120 plus two amino acids on the five prime side of it. So minus two pro PSA, right? And you measure those

01:09:48.540 specific PSA-based proteins in the blood. And the 4K score is great because Andrew Vickers and Hans

01:09:56.000 Lilja developed it with this other great urologist, Peter Scardino, Memorial. And what they looked at

01:10:02.060 was, well, what's the chance that this person is diagnosed with and has high-grade aggressive lethal

01:10:07.840 prostate cancer? And it gives you a percentile chance. So when you get the 4K report, it's actually

01:10:12.760 a really nice report. It'll say 2% chance, 20% chance, and so forth. And so now,

01:10:18.140 as you start using this in your practice, they now also give you the PSA. So you can see the PSA,

01:10:23.560 and then you can say, wait a second, this guy's PSA is 6, but his 4K score is 2. It's safe.

01:10:28.200 What I really like about it is, and so when we do our, usually with our patients in their second year,

01:10:34.980 sometimes in the first year, but usually in their second year, we do a cancer screening

01:10:38.060 program where we kind of walk them through every single cancer that you could possibly die of.

01:10:42.940 And then we go cancer by cancer, risk by risk. And it's a very lengthy process on the back end.

01:10:50.360 For the patient, we simplified it. It takes about 90 minutes to go through it. But for the males,

01:10:55.300 when we come to this, I always view this as one of the better, I said, I wish every cancer had a test

01:11:00.960 like this. Because as we'll come back to, pretty much every guy is going to die with prostate cancer.

01:11:07.080 But fortunately, most men will not die from prostate cancer. Our job is to figure out when

01:11:12.660 a guy has prostate cancer, as you alluded to earlier, is this the bad one? Or is this the one

01:11:17.160 that if you muck around with it too much? And so what I guess Vickers and his team have been able

01:11:21.720 to do is figure out that there's now enough data that you can basically turn this into a binary test.

01:11:27.720 So PSA would be a continuous variable. And when you want to test the sensitivity and specificity of

01:11:34.720 a continuous variable, you have to use something called a receiver operating characteristic curve.

01:11:38.840 And it becomes quite complicated because the question becomes what cutoff. And as you alluded

01:11:43.420 to, it's very difficult with PSA because it has to be age and volume adjusted. So now it's a

01:11:49.480 three-dimensional receiver operating characteristic curve where you would have a different AUC,

01:11:54.600 area under the curve, for each point in time and volume. I mean, that becomes almost inconceivable.

01:12:01.540 And yet the 4K has basically allowed us to say the following. If your 4K score is less than 7.5%,

01:12:09.880 and I might butcher the numbers a little bit, but if it's less than 0.5%, the probability that you

01:12:15.360 will be alive, the probability that you will die of metastatic prostate cancer is 1.6% in the next

01:12:22.020 20 years. Yeah. It's almost the lifetime of the patient. And that's based on this data from Andrew's

01:12:27.920 partner, a co-developer, Hans Lilja, where they had this incredible database from Malmo, Sweden. So

01:12:34.520 they could track it. And then the reverse is if you're greater than 7.5%, I think it's like 16% or

01:12:39.900 17% chance in 20 years. The binary cutoff is 7.5%. But it's a continuous variable.

01:12:47.260 But above that, it's continuous. It's not like if you're above that, it's a 50%. So it varies based

01:12:52.500 on the number. So where are we today? Let's take a journey backwards in time. In the late 1980s,

01:12:59.960 40% of men who were coming in with prostate cancer had metastatic at the time of presentation,

01:13:08.400 just like a lot of cancers, other cancers that we diagnosed today. And that was how it was then.

01:13:15.320 There was an epidemic of deaths from prostate cancer. We were getting a better handle on how to control

01:13:20.420 cardiovascular deaths. People were coming in with aggressive advanced cancers. Prostate was one of

01:13:26.640 them. Tom Stamey took this PSA test and he first made the observation that you could use it to

01:13:35.000 actually follow men after their cancer treatment. And if the number went up, gosh, that meant that

01:13:40.500 their cancer was back. It was just a game changer, right? This is the first time this was ever done.

01:13:44.500 And then Bill Catalona, who's one of my partners here, one of the other godfathers in the field,

01:13:50.360 he said, why don't we use it to screen people to pick up cancers when they're early and curable,

01:13:54.940 not when they come in in advanced. So the change-

01:13:58.520 And what year was that? That would have been-

01:13:59.840 A 1990 FDA approval. So they set up arbitrary cutoffs. This is what this idea of mass screening

01:14:07.940 took off. And it's been sold to the public like, well, the urologists were out there just to make

01:14:13.680 money. This is what we are doing to get rich. No, it wasn't that. It was because at the time the test

01:14:19.260 was developed, it was the first biomarker for cancer. Pick up a cancer early. If you pick it up,

01:14:25.320 treat it and cure that patient. Now, over the 1990s and early 2000s, what we realized is, well, guess what?

01:14:33.320 We're picking up a lot of cancers. We're treating a lot of cancers. Number one, we're increasing and

01:14:39.260 reducing the deaths from prostate cancer. We're reducing the incidence of metastatic

01:14:44.640 prostate cancer at presentation. It was 40% in basically 1990, 40% of men coming in with

01:14:52.020 prostate cancer metastatic at the time. By 2000, it was 4%.

01:14:56.580 Now, the skeptic is going to say, and this is such a controversial topic, so it's so good that we're

01:15:01.840 doing this. The skeptic will say, well, that's just lead time bias. I mean, all you did was catch a

01:15:06.980 bunch of men earlier, so you have a much bigger funnel, right?

01:15:10.540 Right.

01:15:11.080 So, by the way, the same controversy exists on mammography, so I can't wait to actually sit

01:15:15.980 down with the Ted Schaefer equivalent of breast cancer at some point because I realized that an

01:15:20.180 episode like this is probably a little bit more geared towards male listeners or probably the

01:15:25.120 female listeners who have male spouses or people that care about going through this. But it's interesting

01:15:30.500 to watch the rise of mammography and the rise of PSA go through this parallel thing.

01:15:35.400 And colonoscopy, though, to a slightly lesser extent, but really being the big three mass

01:15:40.700 employed screening tools.

01:15:42.100 Well, it's been written about.

01:15:43.520 Yeah, and you've written about this.

01:15:44.900 Well, Peter Albertson is another Hopkins alum. He's a chair at Connecticut, and he's an anti-screener

01:15:50.440 effectively for prostate cancer. And he wrote about this. And he showed that if you just look at

01:15:55.240 incidents of metastatic prostate cancer, incidents of metastatic breast cancer, there's no change with

01:16:01.100 the implementation of mammography. There's a huge drop in the incidence of metastatic prostate cancer

01:16:06.560 with the implementation of PSA screening.

01:16:07.700 So why is he an anti-screener?

01:16:09.620 Well, he just, he was. Historically, he wrote this paper and showed that there was a huge difference.

01:16:15.720 So now, with screening, you have increased detection. And what we've learned is unlike, let's say,

01:16:23.740 pancreatic cancer, where most of the time, if you picked it up early, if you did nothing,

01:16:28.620 you would die. Not everybody who has prostate cancer has a lethal variation of it.

01:16:34.380 And so, initially, we developed a biomarker to pick up all prostate cancers. That was the PSA

01:16:40.580 blood test. We picked them up. We treated them. We reduced deaths. We also over-treated people,

01:16:47.160 people who had a cancer that would never have been lethal in their lifetime. That's the dying with,

01:16:52.400 not the dying from.

01:16:53.720 And this is something you and I used to talk about nearly 20 years ago. I remember

01:16:58.320 sitting in the cafeteria because, you know, even though, you know, we were still interns and

01:17:03.020 basically two knuckleheads, you knew you were going to do this. And you were always

01:17:06.940 head and shoulders above everybody else in terms of what you understood. I remember asking you,

01:17:09.600 I was like, I don't get it. Like, why do some guys get prostate cancer? And it seems to be

01:17:14.800 relatively uninteresting. Like, and other guys get it and they're dead in two years and it's as

01:17:22.060 devastating as pancreatic cancer. What is it about the biology of that? Because it strikes me as more

01:17:28.180 a function of the biology than the environment, you know, or the host. But I could be wrong,

01:17:33.760 of course. But I remember talking about this a lot and really coming away, scratching my head,

01:17:37.680 thinking, I don't have a clue what's going on with this disease.

01:17:39.880 I mean, I'm still scratching my head about it because that's what my whole research program is

01:17:44.000 all about is, well, what's the molecular biology of lethal prostate cancer? So we'll talk about that in a

01:17:49.060 second. But to circle back to our story, so we diagnosed many men with prostate cancer. We

01:17:55.340 treated men and we saved their lives and reduced deaths from prostate cancer, period. It's not

01:17:59.400 debatable. But along the way, there were people that were pulled in and were treated who did not

01:18:04.120 need treatment. But, you know, there's a lot of smart people who have studied the biology of

01:18:08.420 prostate cancer. And we realized that not everybody who was diagnosed with it needed to be treated from

01:18:13.500 it. And so the 4K score and the prostate health index help us identify men who have life-threatening

01:18:22.120 or lethal, potentially lethal prostate cancers. And so those are great screening tools. They're not

01:18:27.980 considered or the government doesn't like them as first-line screening. So you should, they recommend

01:18:33.240 you do a regular PSA blood test if it's at all abnormal. Remember, 70% of men have normal PSAs

01:18:40.400 if they're such a thing. And by the way, what, do we have a sense of what percentage of those men

01:18:45.060 can still harbor a lethal prostate cancer? Well, Vickers would know that data and they published

01:18:50.380 on that. It depends what you say, normal and not normal is. Below, I mean, a PSA below three,

01:18:56.800 there are still men that have, if you just do one test, it's... Assuming it's not a lab error or you

01:19:02.620 miss something. Yeah. No, no. Below three, I still think the 4K data says it's somewhere around,

01:19:07.660 I want to say 10 or 15%. So it's not a single digit thing. And another big opposition in the

01:19:14.280 screening world is the quote-unquote unnecessary biopsies. And I say quote-unquote not because I'm

01:19:19.120 diminishing or minimizing that, but the idea is, look, a prostate biopsy is a transrectal procedure

01:19:23.580 for most men. It's a morbid procedure. It's not comfortable. And just as it's not comfortable for

01:19:28.580 a woman to have a needle put into her breast. And the fear is, hey, we're doing too many of these.

01:19:33.940 I want to circle back to that, but my view on that today is diffusion-weighted MRI and the MRIs

01:19:41.400 that we have today have really cut back on those biopsies. But I want to get your... That's just

01:19:45.480 my take as a non-urologist with my patients, but I want to come back to that.

01:19:49.480 Well, so the government said in 2008, first for people over 75, and then in 2012 for all men that

01:19:58.200 you shouldn't do PSA testing. And when the internist got to go ahead to not do it, I mean,

01:20:03.880 it's easy to not do it, right? You just don't do it. So what would you predict would happen if you

01:20:08.140 stop screening for prostate cancer?

01:20:09.820 Well, you would predict it would go up and it would depend on the time horizon of the disease.

01:20:14.180 So if you stop screening for prostate cancer, you'd predict that the detection of prostate cancer

01:20:19.860 will go down, right? You're not looking for it.

01:20:22.140 But you're going to have a greater number of late presenting diseases show.

01:20:26.360 More lethal disease. So we published, and some of my good friends in neurology have published that,

01:20:31.300 yes, that in fact has occurred. So if you look at starting in 08 or in 12, when these two big

01:20:37.100 shifts occurred, since that time, there's been a rise in the incidence of more advanced prostate

01:20:44.320 cancer. So the cancers that are picked up today, even with this short window where we stopped

01:20:51.340 screening aggressively with the internists, that there's now more aggressive, more lethal disease.

01:20:55.600 As of today, I still believe that the formal recommendation for screening for prostate cancer

01:21:01.560 is each physician and patient should discuss together. There is no formal recommendation.

01:21:06.640 Because when we go through each cancer with our patients, we show them what the ACA, what the

01:21:12.460 American Cancer Society says, the US Task Force on Preventative Services, the NCI, the New England

01:21:18.360 Journal of Medicine did a review on every cancer. And there's one other one, one other group. Oh,

01:21:21.920 the CDC is the fifth body to weigh in. And we show them, here are the recommendations from all

01:21:27.120 five of these for every cancer. And I remember when that shift changed to, for prostate cancer,

01:21:33.360 there's no more recommendation. Well, the recommendation is talk about it with your

01:21:36.800 doctor, which is a bit of a pass the buck. Besides the, I think the American Academy of

01:21:40.940 family practitioners and they don't recommend PSA screening still. I'm not sure why, but that's a

01:21:48.900 different discussion. But the bottom line is that almost all the guidelines now say it's a shared

01:21:53.680 decision-making process, which I think makes perfect sense. That's how I view modern medicine.

01:21:57.760 Yeah, it does. In theory, it makes great sense. What I worry about, Ted, is there's a bunch of

01:22:02.140 patients that get caught. They don't have doctors like you or me who are willing to be able to have the

01:22:07.160 luxury of the time and the ability to educate themselves to do that? Because I still see a

01:22:11.440 lot of patients that show up and they're not getting screened because their doctor's basically

01:22:16.380 saying, well, obviously this is quote unquote controversial. I sort of remember hearing that

01:22:21.440 we shouldn't have been screening, so we're not going to do it. And that's sort of my fear with

01:22:24.720 these things. Well, I think shared decision-making, it requires, well, so then to me, conceptually,

01:22:30.860 it makes a lot of sense. In reality, what does that actually mean? Well, that's the next question.

01:22:36.200 That's the next unknown, right? Is, well, how's our shared decision-making process? How does it occur?

01:22:41.320 And when a patient sees you, that's different than when a patient sees an average internist,

01:22:47.460 let's say. And it's different when a patient doesn't see any doctor. So, you know, the idea that

01:22:53.620 there's the bus that rolls up that just does your blood work and sends it back to you in the mail,

01:22:57.740 that's terrible. I mean, I did that when I was a resident. They paid me 50 bucks to go man the bus and

01:23:03.100 do that. That's not really doing that patient, those individual men, any, you know, any, they're

01:23:08.180 not helping those people because you don't know their whole health history, you know, and all that.

01:23:12.800 So, I experienced that and, you know, I got into it with Otis Brawley about screening and, you know,

01:23:18.460 he raised that point and it's valid. I did that when I was resident because I was told to do it and

01:23:22.280 it wasn't, that's a mistake, just bringing up the bus and doing blood tests in the Walmart parking lot.

01:23:27.880 That's not a good answer. Having a discussion with the physician is, their internist is a good

01:23:33.620 answer because I have many patients. What were the bus parameters, by the way? Men between age.

01:23:38.300 Any guy who showed up. Literally any dude who shows up could get a free PSA. Yeah.

01:23:43.000 You know, and then they'd say, how did I not know you were doing that? I did it once or twice,

01:23:47.400 you know, when I was a lab year resident and they'd say, go ahead and, you know, do you want to earn 50

01:23:51.320 bucks? And I remember I drove to some civil war town in Northern Virginia. It was a cool town,

01:23:57.400 you know, and did it, you know, on a Saturday for half day. And, you know, I did it, you know,

01:24:01.480 and it was like, in hindsight, you say, okay, I get it. You know, it was worth doing because now I

01:24:05.320 understand how bad that was and what a mistake that was. Now, conversely, I have a lot of patients

01:24:10.680 that roll in. They're super healthy 68 year old guys with PSAs of 20 and they have a bad rectal exam.

01:24:17.980 And they had a PSA when they were 60 and it was three. And, you know, and they'd come in and I've

01:24:24.980 had a couple of experiences where, you know, the spouse is just hysterical because she's like,

01:24:29.760 you know, how could this guy, her husband's internist just stop the test and not discuss

01:24:36.000 it with us. And to be clear, where is the screening recommendation on rectal exam? Well, it's variable.

01:24:42.720 I mean, I think a rectal exam adds value. Many of the kind of internist societies say that you don't

01:24:49.320 necessarily need to do it. I do think it requires experience, but I think it's part of the physical

01:24:53.400 exam. So you should do it. If you do it enough, you'll get an idea for what's really bad and what's

01:24:58.200 not, you know? And so I, I have a lot of really good internists that still do it and they do a

01:25:02.380 great job. And so I think it's regional and it's also varies by the country. I could probably use a

01:25:08.060 tutorial on it, but I, I, I do it a lot and I realized that it's, uh, can you insert like a

01:25:13.320 zipper noise? I'll show you how to do it. Perfect. I want the technique, but I can see that if it's

01:25:19.500 something you're just not doing frequently, if it's something you would only do on someone who

01:25:23.220 shows up with a high PSA, you're not getting the reps. You've got to sort of know what normal

01:25:26.800 feels like. What is it? What is a 20 year old listening to a heart? You know, when you listen,

01:25:30.880 you don't need a 20 year old prostate exam, but you listen to the heart of everybody. And that's how you

01:25:34.700 know when you detect pathology. It's the same trauma. You got all of those. You did. Yeah.

01:25:39.660 In trauma, you got to see a lot of normal prostate. So I think that the guidelines have come to a

01:25:44.500 medium. You know, the pendulum was both ways. I think that prostate biopsies are these days

01:25:50.980 a relatively safe procedure. They're not overly traumatic for men. There are some men that have

01:25:56.900 complications. I think that that's a little bit overly dramatized by people who are anti-screeners.

01:26:02.540 The other thing that urologists are doing today is now doing trans perineal biopsies. So they're

01:26:07.600 not transrectal anymore. So if a patient's listening to this and they need to go and get a prostate

01:26:12.620 biopsy, one of the things I always tell patients is you should always, you know, it's one thing to

01:26:17.220 know what the average complication rates are, this risk of infection, this risk of bleeding. It's also

01:26:22.360 important to ask your practitioner their personal risks because medicine is not homogeneous. It's quite

01:26:27.700 heterogeneous. So what would we say nationally would be the risk of infection or bleeding from

01:26:32.700 a prostate biopsy? Well, I tell people most men have some degree of bleeding after the biopsy.

01:26:37.540 When you have a bowel movement, there may be a little bit of blood. Let's say bleeding that requires

01:26:41.720 intervention. Right. So that's my point. So if you go on blogs about non-anti-screeners,

01:26:48.140 they'll say, oh, you know, 80% of men have bleeding in their rectum and 100% have blood in their urine.

01:26:53.800 Yeah, sure. There may be a little bit of pinkness or redness, or if you do a microscopic exam on the

01:26:57.900 urine, there's blood. That's ridiculous. Of course, you know, you can have that. But is it requiring

01:27:01.880 admission to the hospital? We wrote a paper on that looking in the Medicare age population.

01:27:07.780 The numbers, it's hard because you look at these big data sets, it's hard to know granularity.

01:27:12.400 They say about 7% of individuals will be admitted to the hospital or seen at the ER within 30 days of a

01:27:17.880 biopsy. That number seems high to me. I tell people at our institution, we monitor our biopsy

01:27:23.640 infections. It's 0.4%. Got it. So somebody shows up at Northwestern knowing that seven out of 100

01:27:29.640 guys are going to be back in the hospital a month. And you can say, actually, it's in our hands,

01:27:33.100 in our series, it's four out of 1,000. You feel a heck of a lot better.

01:27:36.960 Yeah, with an infection. I would say that, you know, it's probably about one to 2% show up at the ER

01:27:42.100 or something for an evaluation. They maybe have, because you can have some problems urinating because your

01:27:46.280 prostate can get a little bit swollen. So overall, it's low. You tell them the results. And as you

01:27:52.160 alluded to before, in my practice, you know, I don't biopsy everybody. I biopsy people who I think

01:27:58.460 have clinically significant prostate cancer. So I start with the PHI test. We have it within our

01:28:03.040 system here. And so I use the 4K. Is there any reason to switch from one to the other? Are you

01:28:08.380 pretty agnostic? No, the Hans Lillian and Andrew Vickers show that they perform identically in the same

01:28:14.300 serum? What patients, so the 4K was developed on a cohort of what sounds like pretty homogeneous

01:28:21.160 patients, right? What was the PHI developed on? What was their cohort? Similar. I mean,

01:28:26.220 most of these tests are done and developed in Caucasian men, you know, Northern Europeans.

01:28:30.560 I was going to ask you, do we run a risk here if I have an African-American patient

01:28:34.140 and can I be misled by his 4K? Should I be?

01:28:38.400 Well, that was a good question. And the OPCO team just published a paper based on a validation

01:28:45.100 cohort of VA patients where there was 50% African-American and it performed as well or

01:28:50.800 slightly better. One of my partners here has a prospective trial. It's him and myself looking

01:28:56.280 at PHI in African-American men. And the early take-home message is it looks like it performs

01:29:01.320 as well or better.

01:29:02.560 So this is a gift. I mean, you don't normally get this in biology.

01:29:05.540 Right. This is exactly the kind of test that can go awry because you can get fooled by

01:29:10.040 differences. So I'll give you an example, right? You look at non-alcoholic fatty liver disease and

01:29:14.580 AFLD. I mean, if you want to study that disease in Hispanics and then try to make even the mildest

01:29:20.900 inference about what's going on in African-Americans, you're hosed. I mean, they're not even the same

01:29:24.780 disease. In fact, even diabetes is quite different across races. So to think that something as

01:29:30.300 ubiquitous as prostate cancer, even though it might be a different disease, because I know that

01:29:34.040 African-Americans, we're going to talk about this, I'm sure, have a different version of this. But

01:29:37.180 even from a screening standpoint that they could be, you could have one tool that is so good in

01:29:42.020 both. It's fortuitous.

01:29:43.880 Yeah, they're good tools. And then so after, if there's an abnormality in the PHI or 4K score,

01:29:48.440 then I move to an MRI. And then there's been good data.

01:29:53.100 And can you just, because, I mean, we talk, we geek out on this stuff because I'm super nerdy about

01:29:57.980 what type of MRI to do for what thing. But for a patient listening to this, Ted, who's going to go to

01:30:02.480 their doctor and whose doctor is hopefully cooperative enough, what do you recommend?

01:30:07.000 Because not all MRIs are doing the trick here.

01:30:09.760 Yeah. I mean, on paper, what you want is a multi-parametric prostate MRI. The most important

01:30:15.560 phase, the most important parameter in the multi-parametric MRI is actually the diffusion-weighted

01:30:22.120 imaging, which is the most operator-dependent. So it really requires a skilled technician and a

01:30:30.720 skilled interpreter radiologist to look at those DWI images. That's the most important one. So

01:30:36.300 we do give patients contrast, but people have shown you can get a lot of value out of just a

01:30:41.840 non-contrast DWI-based.

01:30:44.180 The one we use, no contrast, but their DWI is exceptional. I've sent you the images. I think

01:30:49.900 if they're Schaefer approved, I'm happy.

01:30:51.780 They're very good, yeah.

01:30:52.540 Yeah. T1, T2, DWI, and a multi-planar MRI. So if you're listening to that, and if your doctor

01:30:58.460 refuses that, I think those are the kinds of things that make me think you need another doctor. Because

01:31:02.480 at this point, and look, your insurance might not cover it. You may have to foot the bill for that,

01:31:06.760 and that's horrible if your insurance wouldn't cover that.

01:31:09.340 That was true, but there's recently reported a large multinational prospective clinical trial

01:31:15.040 looking at the utility of MRI to use for screening for prostate cancer. And the study was,

01:31:21.080 half the men got an MRI, and if there was a suspicious lesion, they got that lesion biopsied.

01:31:26.720 And they increased the detection of high-grade cancer, reduced the over-detection of low-grade

01:31:32.420 prostate cancer. So it was a quote-unquote positive study. We haven't had problems in the Midwest and

01:31:37.080 Illinois getting MRIs approved, but that randomized trial reported out of the UK, that really has

01:31:43.540 changed a lot about what companies are approving for MRIs for screening.

01:31:47.720 That's great to hear.

01:31:48.320 So if somebody has an MRI, if there's an abnormality on the MRI, I'll recommend a biopsy. Now,

01:31:54.700 there's a lot of data that says you shouldn't just sample the suspicious lesion, that you should do

01:32:00.120 the suspicious lesion plus doing a sextant biopsy, or kind of what I tell patients is right, left,

01:32:06.540 top, middle, bottom. That adds value, not just in the detection of cancer, but if someone is going to

01:32:13.260 move to surgery, for example, and I don't do a biopsy in a 90-year-old guy, even if they have an

01:32:17.380 abnormal MRI, I do it if I think that person's going to live along long enough to benefit from

01:32:22.080 treatment. In those scenarios, I do those systematic biopsies because I want to know exactly where the

01:32:27.320 extent of the cancer. And one of the problems with MRI is that it doesn't actually see the true

01:32:32.060 boundaries or true borders of the tumors within the prostate very well. So they're often...

01:32:36.260 Especially the DWI because it's not really an anatomic test the way a T1-weighted image is

01:32:40.960 anatomic. That's right. So if you take the lesion on T2, for example, it often undersizes the tumor

01:32:47.360 by between 5 and 10 millimeters. So pretty significant for a prostate, which is generally

01:32:52.360 pretty small. So I do those to get a better roadmap. I put it all together and then I'll talk to the

01:32:58.100 patient about what the treatment should be. So my algorithm is if you have an MRI done and you have

01:33:04.020 an abnormality, you need a biopsy. If you have an MRI done and it's negative, no lesion, but your...

01:33:12.420 This is your quiz for the day, Peter, but what is high? Your PSA density is high. So you have

01:33:19.600 nothing suspicious on MR, but a high PSA density, you need a biopsy.

01:33:24.180 And sorry, in that situation, Ted, do you further stratify by 4K?

01:33:28.000 Well, I have done the 4K or PHI up front.

01:33:30.900 Which was high enough. So you were already talking about a subset of patients who have a high...

01:33:33.960 I think something's going on based on the blood test because 20% of the time...

01:33:37.820 So then you're going to use the...

01:33:38.860 20% of the time, MRI is false negative.

01:33:40.740 Got it. So now you're using the prostate density. And you and I actually shared an email

01:33:44.580 exchange over this about six months later.

01:33:46.000 PSA density is so easy and it is so good. So high PSA density, usually I would say more than 0.15.

01:33:55.520 Depends. Sometimes it's 0.1. Depends on the age of the patient and their scenario.

01:33:59.240 They need a biopsy anyway. And 20% of the time, MRIs are negative.

01:34:02.800 But if they have an MRI, no lesion, low PSA density, they don't need a biopsy.

01:34:09.280 So we published our series on that. It's not a randomized trial. But what we showed was that

01:34:14.840 when we looked and compared the doctors that use that algorithm and those that did not,

01:34:20.300 you reduce biopsies by about one-third. You reduce detection of low-grade cancer by about

01:34:24.600 one-third. And you actually don't compromise the detection of higher-grade disease.

01:34:28.220 So again, we have great tools building off of this very simple PSA blood test

01:34:34.160 to, I think, offer people very sophisticated screening for their prostate cancer. We've

01:34:38.820 talked about that a bunch.

01:34:39.900 Yeah. So let's talk a little bit about the biopsy because every

01:34:42.280 patient here who's had a biopsy or knows somebody who's had a biopsy, there's this word Gleason.

01:34:47.400 Yes.

01:34:47.760 What's your Gleason?

01:34:48.860 Yeah.

01:34:49.140 That could be like a t-shirt.

01:34:51.820 So Donald Gleason.

01:34:52.720 If you guys need to do a fundraiser here, that could be the urology fundraiser at Northwestern.

01:34:56.200 There's a lot of things you could put on t-shirts, yeah.

01:34:58.240 Yeah, yeah. I mean, let's take a step back. So as you know, one of my best friends from

01:35:02.020 medical school, my roommate from medical school, Matt McCormick, is now an excellent urologist

01:35:06.860 up in Reno. And I just saw Matt a couple of weeks ago and we were kind of just, we have a

01:35:11.880 patient in common by total luck. So the patient came to see me and he lives in Reno. And I said,

01:35:17.200 oh, that's so funny. You know, my roommate from med school is up in Reno and his name's Matt

01:35:20.140 McCormick. And he's like, Dr. McCormick is my doctor. I couldn't believe it. Well, what a small

01:35:25.160 world. But I remember in medical school, like one of the things that drew Matt to urology,

01:35:30.140 because we all thought Matt was going to be an orthopedic surgeon. It was just, it's like the

01:35:33.540 most amazing athlete in the history of civilization. Like this guy is going to be an orthopod because

01:35:37.380 that's what you expect your athletes to do. But then when we all started our doing our rotations,

01:35:41.540 he sort of fell in love with urology. And I think a big part of it had to do with two,

01:35:45.260 there were two things. One was it's a field where you can't take yourself that seriously. Like in

01:35:51.000 the end, it's, it's a funny, funny field. Like it's, there's, there's just a lot of dick jokes.

01:35:55.780 There's no way around it. And if you find that, if you don't think that's funny, like you're not

01:36:00.000 going to want to be in that. You got to make it funny. And the second thing was the patients are so

01:36:05.660 grateful. And again, I think if you're a medical student and you're listening to this,

01:36:09.040 you've got to be able to think about what kind of patients you want to interact with. That has a

01:36:14.140 lot to do with your chosen profession. I remember there were people in my class who loved being

01:36:19.580 around older patients and they wanted to go into cardiology for that reason, because they're like,

01:36:23.880 look, my bread and butter, the patient I'm mostly going to see is going to be like my grandmother

01:36:28.740 and my grandfather. And that's, that's why I came to medical school. That's what I love. And that's

01:36:32.760 what I want to do. And there's just something about that urology patient. And again,

01:36:37.180 urology is a broad field because there's male urology, female urology, cancer, non-cancer. But

01:36:41.600 but for the most part, as you said, you get to fix things in people that are causing them real

01:36:47.200 trouble. And again, I'm not minimizing the stuff that I was interested in, which is like pancreatic

01:36:51.660 cancer. But when you take a person's pancreatic cancer out, they don't necessarily feel any better.

01:36:57.080 That's true. They usually feel worse because it's a big surgery.

01:36:59.840 It's a huge operation. And it's a lethal can, I mean, I think that there's a lot of urology that,

01:37:04.140 I mean, look, the patients that we take, the people in urology are great, you know, and so

01:37:09.560 going to work every day is just a blast. I mean, everybody's smart. Everybody's fun. They don't

01:37:14.140 take themselves too seriously. That helps. The patients are wonderful people. They're incredibly

01:37:20.140 grateful. And then urologists also, you know, we own the diagnosis. So a lot of other surgical

01:37:26.640 specialties, let's say colorectal surgery is an example. Very few of the diagnoses come from the

01:37:31.740 colorectal surgeon. And therefore, if you own the diagnoses, you own the pre-treatment, the

01:37:37.620 pre-diagnostic work, you do the intervention, and you follow the patient afterward. And so

01:37:42.820 one of the nice things in urology is that you have this great longitudinal care with patients. And

01:37:47.760 so many of my patients followed me from Baltimore. And, you know, my nurse, Marie, who's fabulous,

01:37:53.480 she hates me because, you know, I'll have like a 15-minute return double book, but it's one of my

01:37:59.200 old Hopkins patients, you know, I'm in the room for two hours, you know, and she's like, what were

01:38:02.160 you doing in there? I'm like, oh, we're talking about their kids and the goats and the whatever,

01:38:05.460 you know. And so that part of it really makes it super fun. I forgot about the goats. Yeah. I love

01:38:10.660 the goats. Yeah. So I've been trying to get goats. Goats are. I've been trying. I'm not winning.

01:38:15.860 What? They're not allowed in your town? No, I just, I can't convince the family to get the goats.

01:38:20.080 Oh my God. You got to go to Pygmy Goat. Cutest thing ever. They're so cute. They stink,

01:38:24.500 but they're super cute. And they're incredibly smart and they're very social. So they do not

01:38:29.860 like, you can't just get one goat. They really, they actually, they don't, they do terribly if

01:38:34.560 they're just by themselves. Yeah. So anyway, so, you know, that's the fun part about urology is you

01:38:39.300 get, you know, you get these patients and they all have a mate every, I mean, I learned, I love just

01:38:42.900 talking to my patients. Dr. Walsh, he had a way to do a history and one of the second thing he asked is

01:38:48.820 what they did for a living. And it wasn't to kind of do a checkbook check. It was just to say,

01:38:53.800 how are you going to talk to this person? And for me, it's, I like to ask them that because I love

01:38:58.360 to just learn about what they do. There's so many cool jobs out there, you know, so, you know, sound

01:39:03.000 engineer for a big theater in Chicago, this or that, it's just awesome. Super cool. Yeah. You've had

01:39:08.700 quite an illustrious career that's not even close to being over, which is also includes, and I know,

01:39:14.140 I know you don't think much about this and I think it's more of a nuisance than anything else, but

01:39:17.460 you've also now basically become the urologist to anyone in power that seems to need, you know,

01:39:24.040 just as Pat was basically when we were at Hopkins, every VIP on the planet came to Hopkins. And I

01:39:30.580 can't, even as a general surgery resident rotating through urology, I can't believe the people that

01:39:36.640 walked through that hospital, which was also true in pancreatic surgery and, you know, all sorts of

01:39:42.340 other surgeries. But, and so of all of the sort of people, I don't, I, again, I don't want to use

01:39:47.020 names because I don't know how many of them have ever publicly talked about it. The only one who I

01:39:50.560 know has publicly talked about it is Ben Stiller, because of course you and Ben went on Howard Stern

01:39:54.100 together. So how did you even get introduced to Ben Stiller? And I know Ben was very private about

01:39:59.080 this for a couple of years. You guys went, if my memory serves me correctly, it was probably a year

01:40:03.460 or two after his surgery that you guys even went on the show together, right? Yeah, it was two years or so

01:40:07.740 after that. And I met him through his internist, this great, really one of the best internists I've

01:40:14.240 ever interacted with, Bernie Kruger. You're telling me like, I don't know who he is. I am. I know. I'm

01:40:18.120 just saying it for the audience. Bernie's great. So for the listener, Ted introduced me to Bernie

01:40:22.460 four or five years ago when I was starting to practice in New York. And he said, Bernie's the

01:40:27.560 best internist I've ever had a referral from, probably because he trained as a medical oncologist,

01:40:32.660 but he said he's really freaking smart and he knows his stuff. And if you're going to be in New

01:40:37.420 York, you got to meet him. So you introduced us. I went to meet Bernie. We hit it off like

01:40:42.660 in seconds. Yeah. And he just said, why don't you just come in my office? And so to this day,

01:40:47.420 I still sit next to Bernie. Bernie's great. So Bernie was taking care of Ben and Bernie was the

01:40:53.280 guy who did all the right stuff. He did the blood work and it was abnormal for him and his age and

01:40:58.640 got biopsied in New York. And then he came and met, he met with Dr. Walsh because Dr. Walsh wrote this,

01:41:04.740 has this amazing book, Dr. Walsh's Guide to Surviving Prostate Cancer. And Ben had gotten it.

01:41:11.100 And so he came down to meet with Walsh, but Walsh wasn't operating anymore at that time.

01:41:15.400 And so that's how I met him was through Bernie and through Walsh. I have a copy of the book for

01:41:20.100 you, by the way, because I convinced Dr. Walsh to do a final, you know, an edition of it just came

01:41:25.220 out in May. It's really, really good. So all the listeners out there, it's a great resource. So

01:41:29.380 that's how we met. And then he had interviewed with a bunch of folks and he decided to have

01:41:34.380 surgery with me, which was, I was honored to be able to do. And then he did great. And so he's been

01:41:40.440 an amazing person for the field because he's not afraid to talk about his journey and what he did. And

01:41:45.980 he really, he's an amazing person. He's just a down to earth, good guy. So for me, I view each of

01:41:52.340 my patients as VIPs, you know, I really honestly, in my heart of hearts do. And so yes, I take care

01:41:59.140 of people who are, you know, important in many different professions and walks of life. And so

01:42:04.480 it's fun to help all of them. And it's fun to go on Howard Stern with Ben Stiller. That was a great

01:42:09.520 experience. Yeah. So by the way, you know, it sort of occurs to me when you say this, that you were

01:42:15.280 still relatively junior as a urologist. You'd probably only been out of your training for six, seven years

01:42:20.460 when you operated on Ben. Did that ruffle any feathers at Hopkins that, that you became the

01:42:25.840 heir apparent? I, I mean, people tell me it did, you know, I never really thought about age in that

01:42:32.440 way. You know, I've always pushed myself to, to be the best surgeon I can be and always tried to

01:42:38.900 measure up to Pat Walsh or one of my other mentors was this guy, Bal Carter. These guys were the

01:42:45.320 brilliant surgeons at Hopkins. And so I, to me, it didn't matter that they had been doing it

01:42:50.420 for 20 years and I had done it for one year. I wanted to be as good as they were, just like,

01:42:55.280 you know, you would the same way. And so that's how I always viewed it. Right. And so,

01:43:00.220 and it was just the environment I surrounded myself with. So for me, when Walsh said, you know,

01:43:05.820 listen, I want you to become my partner and eventually want you to take over my practice.

01:43:10.240 When I started, quote unquote, as his partner, he was still top of his game and was the, was the man.

01:43:16.240 And I benefited from that because he was so busy. I, you know, he would refer me cases and at the

01:43:21.340 very end of, you know, our relationship or time at Hopkins, you know, he wasn't operating anymore.

01:43:25.580 And so I would, if he had patients that needed surgery, I would do it. And everybody, I think

01:43:29.940 on the outside thought that this was this easy thing. It was a gig, but listen, when a guy you

01:43:34.720 operate on not only reports to you, how he's doing, but how to Pat Walsh, how he's doing, then that's

01:43:40.220 serious. You know, you got to be on your game. Yeah. It's like, it's like an eternal fellowship that you

01:43:43.820 never left. Right. That's right. So, you know, he would call me and say, you know,

01:43:47.900 so-and-so says his incision is crooked. And I'm like, oh my God, you know, so like, you know,

01:43:52.440 you couldn't get away with anything. And so it makes you better, right? It definitely makes you

01:43:56.340 better. So let's go back to the t-shirt raffle thing. And what's your Gleason? So what is this

01:44:00.600 Gleason score? So Donald Gleason is a pathologist. He was a pathologist and many people, including the

01:44:06.000 folks at Hopkins were coming up with a way to grade prostate cancer. So we grade cancers and that's a

01:44:13.380 way to measure how aggressive they are. And usually cancers are kind of high grade, low grade, or

01:44:18.160 a one, two, three kind of system. And Gleason came up with a way to grade prostate cancer

01:44:24.720 based on the appearance of the glands. So if you go back to our analogy or discussion of the sewer

01:44:31.260 system, effectively, you know, there are these channels that the prosthetic fluid comes down and

01:44:37.200 out of, and these channels will grow abnormally in a, in a cancerous state. And so Gleason was

01:44:43.660 describing how these channels appeared under the microscope. Now, one of the interesting things

01:44:49.280 about it was, unlike a lot of other cancers where they would describe the grade of a cancer based on

01:44:54.760 a high power view, like a very, very close view, Gleason graded his prostate cancers in a lower power

01:45:01.120 view. So he got a better sense of the...

01:45:03.200 So more of an architecture...

01:45:05.260 It's an architectural thing. So it's the tree, not the leaves. Whereas a lot of grades are the,

01:45:10.060 what does the leaf look like?

01:45:11.000 Yeah, what's the edge of the leaf look like?

01:45:12.540 So, so he did it. And so the way he did it was he said, well, what's the most common looking

01:45:17.780 abnormality? What's the most prevalent abnormality on the view on the, of the tumor? And then what's

01:45:23.740 the second most common kind of glandular architecture? And so the Gleason sum is those two things,

01:45:30.340 the most prevalent, and then the next most prevalent. And that went from, and so it was

01:45:35.280 a one to five scale. So the lowest Gleason score originally, Gleason sum...

01:45:39.080 So there are 10 combinations.

01:45:40.780 Yeah. The lowest Gleason sum would be a two. The highest Gleason sum would be a 10. That was how

01:45:46.300 it started out. But then over time...

01:45:48.640 So meaning a one plus one or a five plus five.

01:45:51.140 That's right. So over time that evolved in the lowest Gleason sum would be a six,

01:45:56.700 a three plus three was the kind of typical read. Meaning because if you're already at the point

01:46:01.860 where you're doing a biopsy, you're not going to see ones. You shouldn't be seeing ones and

01:46:05.500 twos if you're doing a biopsy. Is that the thinking?

01:46:07.480 I think that there were some general organizational architectural features that everybody just agreed

01:46:14.320 were low grade, not aggressive. And yes, you could occasionally, you know, occasionally even at

01:46:19.880 Hopkins, I'd see it on final pathology report at Gleason with some pattern two in it. And they would

01:46:25.840 try to explain to me the subtleties of the difference between a pattern two and a pattern

01:46:28.600 three. I think most pathologists call it a... They would just call it a three. So that's where it

01:46:33.420 was for a long time. But there are some subtle differences in the Gleason sum that actually have

01:46:39.820 real big differences for what the patient's outcomes would be. And so in 2015, in late 2014,

01:46:47.240 the International Society for Urologic Pathologists. So we're talking about dork central here. I mean,

01:46:52.380 you know, real, you know, real super geeks, but really good pathologists. They are kind

01:46:57.020 of people.

01:46:57.320 Yeah. They got together along with radonks, radiation oncologists, medical oncologists,

01:47:02.320 urologists, and said, we need a better way to transmit this information to patients and to

01:47:08.920 internists in a way they can understand. So now there's a great group. And the great group goes

01:47:14.560 between one and five. The original kind of old school Gleason sum of six, that's a one.

01:47:20.760 A Gleason three plus four equals seven is a two. A four plus three equals seven is a three.

01:47:28.080 A four plus four equals eight is a four. Four plus five equals nine. Or five, five is a five.

01:47:34.740 So this stepwise gradation into five bins of aggressiveness called the great group actually

01:47:41.640 translates very nicely into stepwise clinical outcomes. Clinical outcomes. So that's the new

01:47:47.640 kind of way that we talk about it. It's how I talk about with my patients. It's just a great group.

01:47:51.260 So you're a great group one, two, three, four, or five.

01:47:54.000 So do you do any other testing? Do you use like Oncotype or any of these other genetic testing

01:47:59.440 algorithms to further stratify? Or do those only become things that are done post-surgery to determine

01:48:05.980 adjuvant care?

01:48:07.240 So I think that they can, yeah, that's a good question. So I generally speaking, don't

01:48:11.860 test because I think I know what the patient, what they need. So what do I mean by that? Well,

01:48:18.180 you taught me when we were interns, you don't, don't order a test. Don't do a test unless you know

01:48:22.900 what you're, what you're going to.

01:48:23.920 How it will. And yeah, it's so funny. You bring, I was just having this discussion with a patient

01:48:27.300 yesterday.

01:48:27.820 Yeah.

01:48:28.220 Don't order a test if it will not alter your management.

01:48:30.520 Right. So I don't do a prostate biopsy in a 95 year old guy who's got an LVAD. You know,

01:48:35.960 I don't do it. You know? So, you know, I don't.

01:48:39.140 The urology consult to the coronary ICU. You know, so I don't do the test unless it's going

01:48:46.120 to change what I recommend for the patient. So prostate biopsy, I'll do it if I think I should,

01:48:50.600 you know, change something. So I don't do the test unless it's going to change something I

01:48:54.660 recommend. And for me, it's, there's not many cases where it will change what I recommend.

01:48:59.780 And so meaning what do I mean by that? Well, again, we don't actively treat all prostate

01:49:05.960 cancers today. People who have great group one prostate cancer, generally we recommend

01:49:12.080 active surveillance, monitoring the tumor to see if it becomes more aggressive versus.

01:49:17.980 And to be clear, these are patients who, these are the quote unquote Gleason three plus threes.

01:49:22.280 That's right.

01:49:22.920 And we're saying we're going to actively monitor you. And would your, once you have the pathology

01:49:28.400 in your hand, that, that gray group, that gray group or the Gleason score, does anything

01:49:33.340 before that matter anymore? Uh, in other words, does it matter in your thinking that this guy

01:49:39.020 had actually a 4k of 7.5% versus 20%?

01:49:43.440 Yeah, it does matter. And the MRI results matter. So this is the ultimate Bayesian experience.

01:49:49.240 Yeah. I mean, you, you know, that's why the genomic test, it's funny if you measure and you

01:49:54.920 compare a genomic test and there's a bunch of them out there head to head with PSA density,

01:50:01.320 PSA density performs pretty much identically well, right?

01:50:05.480 It's pretty amazing, right?

01:50:06.400 And do you get the grams? I mean, the MRI does a great job at doing that.

01:50:10.960 Do you get that? Can you get that off ultrasound if a patient has an MRI?

01:50:13.600 We measure the ultra at the time of the biopsy, we'll measure it. But the, you know,

01:50:16.820 generally speaking, MRIs is what I use. So a Gleason six, I generally will recommend surveillance

01:50:23.340 unless they're super high volume six. And I know in my brain that, and that's independent of age.

01:50:27.740 So a 40 year old, I mean, we have a mutual patient who was a Gleason seven, I believe at the very

01:50:34.720 young age, like 45, correct? Yeah. Did his age being 45 versus 65 change the way you managed him?

01:50:41.540 Well, so he came in with a single core seven and really wanted to do surveillance. And that would be

01:50:48.740 one opportunity to say, let's do a genomic test on this, on this individual. And let's see how

01:50:53.760 aggressive the tumor looks under the, you know, under the true microscope, the molecular profile,

01:50:58.700 the tumor. And so we talked about doing that and his biopsy, the molecular test was favorable,

01:51:04.460 but you don't forget about those patients. You actually follow them active surveillance.

01:51:09.080 So we re-biopsied him, you know, after a repeat MRI and he had a lot more. His MRI was actually

01:51:16.340 pretty favorable. This was an MRI invisible lesion and he had multi-core seven. So we then,

01:51:23.140 we took him to surgery and he did very well. Yeah. I always think of his case as just one

01:51:26.940 of those examples of, I don't know what the term is because I don't want to use the term precision

01:51:31.160 medicine because that's become so stupid and meaningless. And I don't even want to use the

01:51:35.060 term multidisciplinary because it really wasn't multidisciplinary. It was mostly Schaefer disciplinary,

01:51:39.600 but it, it was, I guess it's just the nuance of the field. It's just, that's, that's the

01:51:44.160 medicine. That's right. Yeah. That's, that's the, that's the hard part. That's the part that you

01:51:48.820 don't necessarily figure out in residency. It's so easy. I think to go through residency, learning

01:51:53.080 the technical stuff, learning the surgical judgment, you know, what do you do if this

01:51:57.740 person's got a postoperative bleed versus an infection and who do you sit on? Who do you take

01:52:01.980 back to the OR? Those are very important skills, but this is like kind of next layer judgment stuff

01:52:07.260 that, um, I mean, aside from talking with your colleagues and surrounding yourself by people

01:52:13.200 who are, you try to surround yourself by people smarter than you. How do you continue that evolution

01:52:17.400 of learning? We have a, what I call adult only journal club every Friday, every other Friday

01:52:22.500 morning. So it's all the oncologists in our group, uh, medonks, radonks, urologists, urologic

01:52:28.940 oncologists. And I call it adult only because it's not really for the residents. It's during their

01:52:33.460 teaching conference and we just pull articles that come up every day. So I, every Friday

01:52:38.100 morning I get a feed from the NIH about new prostate cancer articles, any article with

01:52:43.840 prostate cancer in it. I get that link. It's about 180 to 200 papers a week. I review that

01:52:50.240 list and anything that looks good, I pull it and I'll look at the abstract or I'll pull

01:52:54.020 the paper. And so I send those to the group and on Friday, you know, two days from now, we'll

01:52:59.720 go over my prostate articles plus my partner's bladder cancer articles or kidney cancer articles

01:53:05.660 because I can't, I don't read those. So I have them tell me what's important in those

01:53:09.740 fields. So that's how I, it's really fun. Cause it's just like, you know, what we, it's

01:53:13.620 being in school again, it's being in school. It's this idea of continuous learning. So that's

01:53:18.720 how I think about it and try to keep on top of it. Meetings are okay, but you know, I think

01:53:22.800 that people get bogged down in just the politics of a meeting. So I think reading, reading

01:53:26.900 is what I try to do most of. So let's pivot to another topic that's germane to prostate

01:53:31.200 cancer, which is kind of a two topic that goes hand in hand. The first is the role of

01:53:35.460 testosterone. The second is the role of dihydrotestosterone. So we can explore this in any order, but I

01:53:40.340 want to definitely touch on the notion that is there a real or perceived effect of patients

01:53:47.160 who are on five alpha reductase inhibitors. So for the listener, males make a hormone called

01:53:51.600 testosterone. Testosterone is converted via an enzyme called five alpha reductase into a very

01:53:58.060 similar molecule called dihydrotestosterone abbreviated DHT. DHT is actually a slightly more

01:54:04.020 potent steroid. And in men who 50 times more potent. Yeah. Yeah. So yeah, big deal. Yeah. In men who are

01:54:12.040 susceptible to baldness, DHT drives that process. DHT also probably plays a role in the enlargement of the

01:54:18.480 prostate. Is that correct? Most of the five alpha reductase enzyme is in the prostate. So yes,

01:54:23.660 reducing androgens in the prostate by reducing, effectively reducing DHT production reduces the

01:54:31.740 size of the prostate. So a lot of guys take medication to reduce DHT, either to reduce prostate

01:54:38.300 volume size, so something called benign prostatic hypertrophy, or to minimize hair loss. And it's usually

01:54:44.340 the exact same drug given at slightly different doses. And then sometimes even come up with different

01:54:48.100 names for the same drug. So Proscar is finasteride at five milligrams. And I think Propecia is the

01:54:54.460 one milligram. That's right. Okay. Now I remember many years ago, and I don't, I'm sure this has been

01:54:59.340 revised a hundred times, but maybe 10 years ago, maybe less. But a paper came out that said, look,

01:55:04.820 in guys who have suppressed DHT levels, when they get prostate cancer, they're more high grade. Is that,

01:55:11.900 am I remembering that correctly? And there's been definitely case reports of that. It's hard to

01:55:16.020 really study that over a bit. I got it. But yeah. So what is the current thinking on

01:55:20.380 five alpha productase inhibition and that relationship to prostate cancer?

01:55:24.980 Well, there's, was a very large randomized trial to see if you could take that medication

01:55:30.940 with the idea that if you reduced the relative amount of androgens in the prostate by preventing the

01:55:38.380 production of this potent androgen, DHT, could you reduce the risk of prostate cancer in those men?

01:55:46.020 And the answer was, if you took that medicine that reduced potent androgen, you could.

01:55:50.780 So there was a study- I'm sorry, this was in men starting out who did not have cancer?

01:55:55.200 That's right. So it was called the Prostate Cancer Prevention Trial. And it was over seven

01:55:59.980 years that the trial was conducted. Ian Thompson was the PI on the trial. It was a big study.

01:56:04.920 It did reduce the chance that a man would develop prostate cancer over a reasonable amount of time.

01:56:11.360 But one of the problems was that there was increased detection of more aggressive cancers

01:56:17.080 in the men who are taking the finasteride. And so then the question was, well, what is that from?

01:56:24.620 Is it inducing a more high-grade cancer? You know, and whether or not that's true or not is-

01:56:30.500 Or is it selecting for it because any cancer that comes out of a low DHT environment-

01:56:36.000 Well, yeah. So I personally think that what you were just saying is true. So yes,

01:56:41.180 and there's case reports that people with low testosterone or, for example, people with low

01:56:45.280 PSAs, because PSA is only made when there's testosterone around, for example, that those

01:56:50.660 individuals have more aggressive cancers. Now, this is what I've been focusing on in my lab for

01:56:56.180 like the last four or five years now. And so one of the cool things we did in this collaboration with

01:57:02.220 this company, Genome DX, and this great scientist, Eli Davincioni, was to look at the biology of

01:57:09.720 prostate cancers, how aggressive they were, and compare the aggressiveness of the prostate cancer

01:57:14.880 with the androgen output of the tumor.

01:57:18.740 Another nuanced way to normalize things a bit.

01:57:21.180 Yeah. And so we had this hypothesis that the tumors that had the most amped up androgen signaling,

01:57:29.260 the most androgen output, because prostate cancer is an androgen-driven tumor, that they would be the

01:57:36.180 most aggressive. And I say it that way because you know the answer. It's the exact opposite.

01:57:41.020 The tumors with the lowest androgen output are the most aggressive tumors. So it somewhat relates to PSA,

01:57:49.060 but not entirely like there's not a, it's not a true, you know, linear correlation.

01:57:53.600 So the high androgen output tumors, they can be aggressive, but they are not as aggressive as the

01:58:00.340 ultra low one. So it's this bimodal distribution. And this is a good way to segue talking about these

01:58:05.220 molecular tests because this is a commercially available test from Genome DX.

01:58:08.800 Can I tell a funny story about Eli before we go down there?

01:58:11.140 Sure.

01:58:12.040 I've told this story before, but now we get to put a name to it. So I hope he doesn't like,

01:58:16.780 like, I hope I don't upset him that I'm telling this story.

01:58:19.120 He'll love it.

01:58:19.540 It was, it was, Eli's the guy who called me one day when I was in the airport and he's like,

01:58:24.700 Peter, my wife just got me this book. It's, it's, it's a great book and you're in it.

01:58:29.120 And I was like, what? I had no idea what he was talking about. And he goes, yeah,

01:58:32.660 it's called Biggest Tools. And I was like, wait, do you mean Tools of Titans? He goes, yeah,

01:58:38.460 yeah, yeah, yeah. That's it.

01:58:39.380 That's great.

01:58:42.840 That was Eli. And I know I've told that story. So to this day, like anytime I'm talking with

01:58:48.640 Tim Ferriss, like I'm like, look, I expect to be referred to as the biggest tool.

01:58:52.980 That is, I love that story.

01:58:54.120 Yeah, yeah, yeah.

01:58:54.780 He called me too. He's like, dude, I'm reading this book, but he didn't call it Biggest Tool.

01:58:58.720 That's awesome. That's really funny. So Eli started this company that was, you know,

01:59:03.880 genomically transcriptomically. So looking at the RNA levels within prostate cancers. And so

01:59:08.460 he has a commercial product that's very, very good to just tell you the aggressiveness. It's

01:59:13.360 basically a genomic Leeson score. It's more sophisticated than that, but that's effectively

01:59:17.460 what it helps you to do. But when he, when he looks at each tumor, he captures about 1.4 million

01:59:22.520 data points on each tumor. He uses 20, 21 of them for his test, but we use the other 1.3999 million

01:59:30.660 of those data points. And so we developed this algorithm to look at this. The thing that's

01:59:36.500 pretty cool is we've been able to model and show with Eli's group that, you know, because

01:59:41.220 it's one thing to have a kind of prognostic biomarker, like your prognosis is good or bad,

01:59:46.600 but precision medicine is really the, you know, the predictive stuff. So we've been able to take

01:59:52.220 all this data. We've been able to show that these low androgen output tumors are the most

01:59:57.640 aggressive tumors. Now high androgen output, very high AR output tumors are also aggressive,

02:00:03.300 but as you would imagine, the tumors are sensitive to different drugs. So a high AR output tumor,

02:00:10.440 they're exquisitely sensitive to androgen deprivation, which is one of the main states

02:00:14.180 of treatment for metastatic prostate cancer. Low androgen output tumors are not, right? They're

02:00:19.580 not dependent on it. They don't use it as their fuel for growth. And we've been able to model

02:00:23.820 other compounds that they are sensitive to. And so we're moving those things into clinical trials.

02:00:30.000 It's actually pretty exciting times. So what is the current state of the art or the current thinking

02:00:35.500 on testosterone replacement therapy? And again, I'm referring to this in the, in the confines of

02:00:41.660 what we would call physiologic testosterone replacement. So you've got a guy who's walking

02:00:44.800 around with a free testosterone at seven nanograms per deciliter on a lab where the upper range would

02:00:49.760 be 25 and, you know, he's replaced to 20. My reading of the literature says I'd have a very hard

02:00:55.740 time making the case that that's increasing his risk of prostate cancer. I agree with that. And I

02:00:59.760 think my data suggests that the tumors that, you know, we don't know how they develop, but the tumor

02:01:04.840 where we, we segued like five times, but the idea is that our data shows us that the most aggressive

02:01:09.880 tumors are the ones that have low androgen output. Now, does that mean that they developed in a low

02:01:15.520 androgen state? Maybe. We don't know. But I mean, we don't know, but, but for sure it's telling me

02:01:22.160 that I don't, and like you said, I mean, the literature that we've discussed on the phone

02:01:26.100 many times, I don't see any clear evidence that physiologic replacement of testosterone is going

02:01:31.820 to accelerate or cause a cancer to develop. What do you think the role is of estradiol in this?

02:01:38.620 Some have argued that as estradiol is going up, that may be playing a greater role in prostate

02:01:45.160 cancer, either through its direct interaction or indirectly through its receptors. I think I don't

02:01:51.920 know the answer to that question, but I do know that it's not just a testosterone thing. Remember,

02:01:58.760 when we just talk about benign urologic conditions, testosterone values decline over time. And I

02:02:05.540 oversimplified the whole PSA discussion earlier. So remember that PSAs rise over time, but at that same

02:02:13.480 time, testosterone values are declining. So I do think that a lot of the prosthetic growth,

02:02:19.400 not cancerous growth necessarily, but benign growth are influenced by the ratios of T to E,

02:02:26.600 so to speak. Testosterone to estrogens, you know, androgens to estrogens, which ones-

02:02:32.240 Yeah, because it seems to me that you're at your highest risk when your testosterone is going down

02:02:36.360 and your estrogen is going up. Yeah. Now the question is, what's the lag time?

02:02:39.720 Yeah. So in real time, yes, that's true. But we know that all cancers, prostate cancer for sure

02:02:46.860 among them is something that occurs from mutations to the DNA from decades prior, probably. So yes,

02:02:54.200 at the time of diagnoses, there's probably higher estradiol, lower T, but I think about it like,

02:03:01.560 what happened to that in that patient 10 years beforehand or 15 years? Is there anything about

02:03:06.400 the mitochondria in the prostate? I mean, the prostate has so many odd things about it, and

02:03:10.780 we're going to talk about the difficulty with immune surveillance in a moment, but is there

02:03:14.740 anything about the mitochondria within the prostate that are unusually sort of either ramped up or ramped

02:03:20.180 down relative to other epithelial cell-derived tissues? Yeah, that's a great question. And-

02:03:26.340 Ted, I hope you know, I try to ask great questions here, man.

02:03:28.980 I say that because we just had, last Saturday, we had our kind of a prostate cancer working group

02:03:34.880 meeting where all the kind of, you know, deep thinkers get together. We got together on a

02:03:39.300 Saturday. Yeah, I was just about to say, the fact that you guys did this on a Saturday is just another

02:03:42.880 bit of evidence to like the level of obsession here that I love.

02:03:47.320 Yeah. So I roped in this brilliant radiation oncologist named David Gaius. He works on hormonal

02:03:53.740 dependency in breast cancer, and what he focuses on is on the mitochondria, and specifically these

02:04:00.540 superoxide dismutases that really get rid of reactive oxygen species. And so he has a whole

02:04:07.020 model, and he knows about luminal B breast cancers and how they can become resistant to tamoxifen

02:04:12.480 and so forth. And it's driven by basically the mitochondria.

02:04:17.020 Do the mitochondria in the prostate cancer follow the Warburg effect? Do they become more,

02:04:22.920 do they favor anaerobic metabolism over oxidative phosphorylation?

02:04:27.740 You know, it's hard. People don't, we don't know. You know, people don't know a lot about

02:04:32.700 the metabolic environment of the prostate. I've had a lot of thoughts about where,

02:04:38.180 what about the, I mean, it's a very dense organ. There's not a lot of blood vessels in it.

02:04:43.860 It's not a big blood supply. You know, and so I've thought a lot about just, for example,

02:04:49.380 are there regional differences in the pH within the prostate? And is that what's causing these?

02:04:55.580 Because I think about it in relationship to these androgen-dependent tumors.

02:04:59.220 My brain has defaulted to this idea that, well, the high AR output tumors are ones that are occurring

02:05:05.160 in oxygen-rich parts of the prostate. I mean, I don't know why. Just assume that, you know,

02:05:10.080 and that these lower AR output tumors are occurring in regions of the prostate that have lower PaO2s,

02:05:16.060 different pHs, and they're forced to use an alternate growth pathway. It's hard to test that.

02:05:22.040 You know, I've thought a lot about it. There's nothing published on it, really. It's hard to test

02:05:26.340 it. But this guy, David Gaius, has a lot of really interesting data looking at the sirtunin pathways

02:05:32.340 through mitochondria, regulating the hormonal dependency or hormonal regulation of prostate

02:05:39.820 cancer. It's a brand new area for him. So in other words, the sirtuins, which of course can either

02:05:44.280 turn on or turn off genes, the idea is, and this is SIRT2 or a different? SIRT3.

02:05:49.320 SIRT3. I see. So it could be up-regulating or down-regulating androgen production, basically.

02:05:54.320 He has a SIRT3 manganese superoxide dismutase pathway worked out, and it regulates resistance

02:06:02.560 to tamoxifen and luminal B breast cancer. So, and he's made these observations. He first published

02:06:08.500 this in Cell in, I want to say, 07, 08 on sirtunin-3 in breast, but he's had some data in

02:06:15.620 there in prostate. So I kind of, I hang out with him when I want to hang out with like a deep thinker.

02:06:20.720 So he has this preliminary data and he has some more interesting data that there may be a role

02:06:25.500 for this. So I do think that there's something about metabolism in the prostate. I think it's

02:06:32.800 hard to study. You know, it's a tough, it's hard to model that in a mouse at all. Like you can't do it.

02:06:37.780 You cannot model in a mouse. But I do think that there's some good people on campus here who think

02:06:43.420 about it and are going to be able to study it well. He's, he's the guy. You know, I'm seeing Nav

02:06:47.220 Chandel tomorrow who is a mutual friend. Didn't you go to med school with Nav? Or I mean, you were,

02:06:52.220 he was in grad school when you were in med school or something, right?

02:06:54.240 He says that he was my TA in undergrad, but I just know, you know, I've known him. I think we

02:07:00.000 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

02:07:06.280 have, you know.

02:07:07.140 Anything I should know about Nav? Well, I mean, I know him of course, because we played

02:07:10.340 patty cakes on Easter Island for a while.

02:07:12.340 Well, what, do you know what his nickname is?

02:07:14.020 No, that's the thing. There was a nickname.

02:07:15.500 Yeah.

02:07:15.940 What's his nickname?

02:07:16.800 Well, just for the listeners, Navdeep is this, he's about what, six foot three.

02:07:21.520 Very suave, good looking.

02:07:23.640 Yes. Good looking guy, long hair. So his nickname was Suave Deep.

02:07:30.000 I mean, I've never seen a TA, TA class where there was, it was like 90% women, you know,

02:07:36.140 who had questions for him afterward, you know, you know, it was awesome in med school.

02:07:40.740 He's great.

02:07:41.460 Now, and did you also go to school with Matthew Vanderheiden?

02:07:44.440 I did. He was the smartest kid in my med school class.

02:07:47.140 Yeah. Matthew's, I mean, I know Matthew, obviously not as well as you, but-

02:07:50.760 I don't know him that well. I just know him and Nav really broke open the field of cancer

02:07:54.840 metabolism.

02:07:55.940 Yeah. I'll be, I got to get out to Boston to see Matthew, who actually works and collaborates

02:08:00.840 very closely with another very, very close friend of mine from medical school named Mark

02:08:03.840 Pomerantz, who's a medical oncologist.

02:08:05.060 Yeah, I know Mark.

02:08:05.660 Yeah. He's great. I love that all, like all of these independent circles of my life have

02:08:11.180 overlapped in prostate cancer and cancer in general.

02:08:13.640 Yeah.

02:08:14.200 What is the most exciting area of research that you think of with respect to prostate cancer

02:08:20.080 specifically? Maybe I'll even prime the question by saying immunotherapy seems to finally be coming

02:08:26.240 into its own a little bit with some cancers. But of course the prostate's kind of a weird immune

02:08:31.300 unprotected odd organ, like does immunotherapy play a role in this or are we talking metabolic

02:08:37.820 therapies or is it all going to be coming down to earlier detection of lethal cancers?

02:08:43.420 Certainly early detection of lethal cancers is important. I think the most exciting stuff

02:08:47.700 in urologic oncology is really moving beyond these prognostic biomarkers to predictive biomarkers.

02:08:55.680 And so there's a lot of really cool new things that are, you know, great. So there are some

02:09:01.060 predictive biomarkers that you can pick up in the DNA of a tumor or the DNA of a patient,

02:09:06.940 particularly BRCA1, BRCA2, ATM loss, these different kinds of DNA damage repair pathways

02:09:12.980 that people didn't really think matter for prostate. We now know within the last three

02:09:17.160 years that they really matter.

02:09:18.200 So I didn't, that's news to me. I never really understood that BRCA1, BRCA2 should be looked

02:09:23.200 for in males as well. I mean, I did from a breast cancer standpoint, but not from a prostate

02:09:27.620 cancer standpoint.

02:09:28.300 Yeah. So there's one of my heroes in neurologic oncology is this guy, Pete Nelson. He's at the

02:09:35.880 Hutch in Seattle. And he published a paper and they looked at the germ lines of men with metastatic

02:09:42.800 castrate resistance, so the most end-stage prostate cancer. And what they showed was that in contrast to

02:09:49.120 the general population of men that mutations in these different DNA repair pathways were

02:09:56.000 significantly enriched in individuals who had metastatic prostate cancer. So about 11 to 12%

02:10:00.900 of men with metastatic castrate resistant prostate cancer had mutations, particularly BRCA2, BRCA1,

02:10:07.040 ATM, RAD51, these different pathways that are involved in DNA damage repair. If you look in the tumors

02:10:13.360 of men with metastatic castrate resistant prostate cancer, it, depending on where you look over one

02:10:19.600 third of the tumors, the cells will have mutations in these pathways, which makes them incredibly

02:10:25.140 sensitive to PARP inhibition. So that's a huge game changer. The other thing that people now look at is

02:10:31.580 kind of the total genomic score or the alterations in the genome of the individual cancer cells. And will

02:10:37.700 that make them more sensitive to immunotherapy or not? That's more coming online. But the idea that

02:10:43.280 there are things in the somatic DNA of the tumor cells and in the germline of individuals

02:10:49.180 that you can use to screen for not only, you know, prostate, but breast, pancreas, etc.

02:10:55.240 That's a huge game changer. And then as we touched on earlier, those are not just prognostic

02:11:00.660 biomarkers, but they're predictive of drug response, which is pretty amazing. And then I think Eli's test,

02:11:06.860 the version 2.0 or the beta version of it, which has a lot of these built-in biomarkers that predict

02:11:12.840 response to drugs that now are being tested in clinical trials with the idea that let's test

02:11:17.820 the ability to predict response. It's pretty amazing stuff, actually.

02:11:21.660 So obviously you specialize in prostate cancer. The field of urology is so much bigger than that,

02:11:27.340 right? We haven't even talked about renal cancer, bladder cancer, and to do so would only be to do

02:11:32.220 it an injustice. You know, given that we've been, you know, talking for a little while, and I know

02:11:36.780 you've got a hard stop here in about 20 minutes, I want to talk a little bit about benign stuff.

02:11:41.560 So I'll tell a very personal, maybe somewhat embarrassing story, but it's a good illustration

02:11:45.840 of this. Is that when you were treated at the extra large penis clinic at Hopkins?

02:11:51.640 This is the micropenis clinic.

02:11:52.520 You had the penile reduction surgery?

02:11:53.540 Yeah, the penile reduction surgery clinic, right?

02:11:55.180 Exactly. See, those are the kind of jokes we can only tell in the urology office.

02:11:58.320 Urology, yeah.

02:11:59.280 So about two years ago, I remember calling you and I was like, Ted, I don't know what's going on,

02:12:02.580 man. Every time I pee, like it's just burning like crazy. I did a quick check. I don't have a UTI.

02:12:08.400 I've never had a UTI. It seems unlikely I would. I've been fumbling around and I'm wondering,

02:12:13.120 I must have prostatitis, right? And I guess my question is, Ted, what antibiotics should I take?

02:12:19.080 And I remember I was actually in Baltimore at the time, but I was heading up back to New York

02:12:25.300 because I was going to work in New York that week where I spent quite a bit of time. And you said,

02:12:30.420 well, first of all, you're in luck because my dad wrote the paper on prostatitis. And it's,

02:12:35.220 I forget what year it was, but it was in the England Journal of Medicine. And I downloaded

02:12:38.760 the paper and I read it on the train ride up to New York or maybe I was still in Baltimore because

02:12:44.700 I remember you had, anyway, you'd written me for some Flomax, blah, blah, blah. The long and short

02:12:47.820 of it was I came away from reading the paper and I said, well, my takeaway on this is I need a

02:12:52.300 prostatic massage, not an antibiotic. And you said, yep. So go ask Bernie to give you a prostatic

02:12:57.980 massage. And I had been in pain for a month.

02:13:01.020 And he, we had, he did that to get a sample from the prostate. Cause when you do a urine,

02:13:06.640 urine check for an infection, you're sampling predominantly the fluid, the urine in the

02:13:11.180 bladder. So I said, yeah, fine. Your urine culture is negative, but let's check your prostatic

02:13:16.420 fluid for an infection. I think it was clear, but it was clear. And here's the amazing part of the

02:13:22.700 story. I had been suffering for a month and Bernie being the great Bernie, like he didn't just give me

02:13:28.660 a little bit of a prostatic massage. I mean, he eviscerated me. I, it was one of those Chevy

02:13:34.200 chase moments where I was like using the whole fist there, doc, moon river. I actually, I will

02:13:40.860 say it was one of the most painful things I'd ever experienced. I just, this was, this was a

02:13:44.300 different level of, of pain because it wasn't the rectal. It was like the prostatic massage

02:13:48.760 to, to generate the fluid sensitive. Yeah. Yeah. Especially when you're inflamed,

02:13:53.280 as I would later come to realize, well, here's the most amazing part of that story. Within about

02:13:56.960 three days, everything was better. Yeah. I didn't need a single antibiotic and somehow that massage

02:14:02.420 probably, you know, somehow turned over some of that inflammation or, you know, there was something,

02:14:08.780 yeah. I mean, you, we had you on some anti-inflammatories and we had you on some

02:14:12.740 other symptomatic stuff, but yeah, I mean, it definitely, you know, so we don't really call it

02:14:18.360 prostatitis anymore. We, it's kind of binned into kind of this chronic pelvic pain syndrome kind of

02:14:25.020 concept, but within that concept, you can get acute bacterial prostatitis. That's what happens for

02:14:32.320 people after prostate biopsies and they get very, very, very sick. High, high fevers, 103, 104, like,

02:14:38.420 you know, bad stuff. That's an incredibly rare thing, but what you can get is basically non-bacterial

02:14:44.440 prostatitis, inflammation in the prostate. We don't. That's the thing I think a lot of people

02:14:49.820 don't understand. Itis means inflammation. That's right. You can get itis with an infection,

02:14:54.960 but itis does not imply inflection. So prostatitis, mastitis, these things don't necessarily imply

02:15:00.060 that there's a bacterial infection. That's right. It can be sterile. Right. So people will have, you

02:15:05.120 know, acute inflammation in their, in your prostate, which is what I thought you had on the phone. I

02:15:09.540 said, look, have Bernie do a actual culture of the, of the prostate. Then typically for most people

02:15:15.580 that goes away, we don't know what causes it. You know, we don't know what is that's causing

02:15:20.640 that inflammation. That's what, you know, my father is a very prominent researcher in this

02:15:24.400 field. That's what he works on, but we know we can, we try to treat the symptoms and ride it out.

02:15:30.220 And then we, you know, and then we try to adjust risks that, you know, we prevent it kind of from

02:15:34.440 coming back and so forth. So some of the things that can cause it, you know, we talked about this,

02:15:38.840 you know, constipation. So if you, one of the ways it's easy to get constipated is just go on a

02:15:43.820 transcontinental flight because the air is dry and you know, it's just those little, those little

02:15:48.280 subtle changes make a big difference. So, so those things come into play. Now that falls within this

02:15:53.980 greater scope of something called chronic pelvic pain, which is a, I know a field that is, you know,

02:16:00.960 has some work in it, but it's still evolving. It's really just been recently described. My father

02:16:05.100 was one of the people who described that with some other folks. And so, you know, that involves,

02:16:09.520 you know, just burning or pain in the, you know, the urethra and the bladder. Women,

02:16:14.760 it used to be called interstitial cystitis in women. So some foods will trigger these things.

02:16:19.620 We don't have a good handle on it at all. So we try to manage the symptoms. And then from there,

02:16:24.920 we, you know, try to just prevent. What's the state of the art with using injections within the

02:16:29.780 bladder of Botox to alleviate women who have interstitial cystitis? Some discussion about that.

02:16:35.120 Yeah. It's not, we do, we use Botox in the bladder for people who have, you know, hyper contractility

02:16:42.560 of the bladder, but we don't use it for people who have interstitial cystitis. For people, there are

02:16:47.660 people that have deep seated infections in their prostate that we can document, or sometimes we can't

02:16:54.320 document, but we have a suspicion of them. And in those individuals, you can, you can actually

02:16:58.880 directly inject antibiotics into the prostate. Or in fact, my, my feeling is that actually the

02:17:06.680 typical nidus for this persistent infection is actually the seminal vesicle, which is attached

02:17:11.680 to the prostate. So what, you know, we'll have these individuals who will have recurrent bacterial

02:17:16.260 infections, same bacteria, same sensitivity to the drugs. So they don't become resistant.

02:17:22.240 They're equally sensitive all along.

02:17:24.180 So there has to be a bacteria that you aren't clearing that's outside of the field of scope.

02:17:27.700 That's right. And so, and I feel like those are often, or you can, you can't get the

02:17:32.380 concentration high enough into that, into that tissue. And so there, those cases will do intro.

02:17:38.940 So how, is it difficult? You do that, um, transrectally, transrectally or perineal,

02:17:42.980 but it's, you know, it actually works under ultrasound guidance. And how easy is it to hit a

02:17:47.560 seminal vesicle? Super easy. Even your, even you could do it. Even I could do it. Yeah.

02:17:52.060 That's hard. Let's do it. Let's go across the street.

02:17:53.600 I was going to ask you about that. So thanks for bringing that up. I was going to ask you about,

02:17:58.420 um, you should come in. You need to do, come do a share day with me. Wouldn't that be awesome?

02:18:02.980 You've never actually been on the robot. Have you?

02:18:05.160 No.

02:18:05.640 We got to do it. We got to go, man.

02:18:07.760 How many? Yeah. Going back to that for a second. So, I mean, we didn't really get into the deep

02:18:11.800 surgical technique, but I do want to link to any videos that we can, but what percentage of your

02:18:15.980 prostatectomies do you now use the robot for versus open?

02:18:18.720 A hundred percent. You're a hundred percent robot now?

02:18:20.920 Yeah. And Moe's a hundred percent robot, obviously. So most men now getting their

02:18:25.600 prostate removed will do it via the robot. I mean, I think that there are very few people

02:18:30.320 out there that actually can comment on which one is better, you know, robot versus traditional open.

02:18:35.860 But I've done, I don't know, 1500 opens and 2,500 robots. So I have a good idea for which ones are

02:18:42.120 better. When was the last time you did an open case?

02:18:44.820 Three years ago, two years ago.

02:18:46.140 Is there a part of you that's sad that like, if you went back and did an open tomorrow,

02:18:49.980 you wouldn't be as good?

02:18:50.820 I wouldn't be as good, but even when I was good robots, I'm better using the robot.

02:18:56.420 It's just incredibly precise. I'm just a super type A guy. You know, you get four arms to control.

02:19:02.780 I only got two hands, right? So, you know, you can just retract everything exactly the way you want

02:19:07.340 it. The magnification, the optics are just unbelievable. And you would just die.

02:19:14.500 Anyway, it's just like-

02:19:15.760 Is it still the DaVinci?

02:19:16.700 Yeah. It's like wearing 20X loops. You think about it, you know, you had your 2.5s that

02:19:21.720 you used to walk around with.

02:19:23.060 Hey, hey, hey, I upgraded to 3.5.

02:19:25.620 Those are tough. I had some 4Xs and it's harder, but it's amazing, right?

02:19:30.240 Well, it depends on the case.

02:19:31.120 Yeah, but even anything, I mean, I wear my loops for every open case I did, but, you know,

02:19:37.460 even, you know, the difference between 2.5 and 3.5 is a big difference. So think about

02:19:41.920 10X.

02:19:42.680 I just put a 4X magnifier on my bow. So you have a clarifier in that sits in the peep and

02:19:49.600 then you have like a magnifier that sits on your scope. And I'd been shooting probably

02:19:54.560 up to 70 yards naked. And then I went to a 2X and I was like, oh, this is good. And then

02:19:59.720 I went to the 4X and I just don't know if I could ever go back.

02:20:03.560 That's the thing. I was, you know, one of my mentors, surgical mentors is this guy,

02:20:07.260 Bal Carter. And he always did his cases with, you know, without loops. And then he's, and then,

02:20:12.700 you know, Pat made him switch. And so we would talk about it and he said, you know, it's just

02:20:16.980 literally a different operation. And so people who do open prostates without loops, I don't know

02:20:22.840 what they're doing. Cause I mean, you know, you just see everything, right? You see it all.

02:20:27.160 Now think about the robot. I mean, I can dissect out individual little arteries that are one,

02:20:31.780 two millimeters.

02:20:32.760 Has this made it difficult to teach residents?

02:20:34.860 It's easier to teach them. You got to come, come by tomorrow. I'm doing a case. Seriously.

02:20:39.360 I'm talking to Nav tomorrow. How am I supposed to do that?

02:20:41.660 Not at 7 a.m. That boy doesn't roll out of bed before nine.

02:20:46.980 I'm going to have to take you up on that.

02:20:48.280 Yeah.

02:20:48.880 There's a lot of other stuff I want to talk about. I know we're getting real close to,

02:20:51.640 you've got a hard stop in 10 minutes now. Do you know anything about male contraceptives?

02:20:55.620 Is this a topic that, uh, is there, is there a male contraceptive on the horizon outside of a

02:21:00.160 vasectomy?

02:21:00.760 I mean, the only way to really prevent sperm production is to block testosterone in the

02:21:06.300 testicle. So that's the way to do it. And, you know, there's a couple that are coming online.

02:21:12.340 They've been tested in smaller groups of men. I don't know if they're really ready for prime

02:21:16.060 time. And I don't know if men are ready for that. You know, what about vasectomies?

02:21:20.400 They work.

02:21:21.000 What's the reversal rate on them if you need to worry about that?

02:21:23.320 Well, I mean, I have a partner here, Bob Brannigan, who's, you know, he's one of the,

02:21:26.940 he's one of the top three guys in the country. And, you know, yeah, if it's the right, if it's,

02:21:31.280 if the vasectomy was done correctly the first time, you know, by a professional, so to speak.

02:21:35.720 So not in the parking lot.

02:21:37.720 There's, there's a surgeon. I'm not going to mention it.

02:21:40.420 What do you mean by a professional? Who else is doing vasectomies out there?

02:21:44.300 GB. There's a guy who just think about, there was a surgeon in Hopkins, you know what I'm

02:21:49.500 talking about?

02:21:49.740 Yeah. Yeah. Yeah. Okay. I'm not saying he did them, but if there was a urologist like

02:21:53.560 him.

02:21:54.020 Yeah. Yeah. Nickname, Hodad, hands of death and destruction. Anyone, any Hopkins resident

02:22:01.340 from our era listening to this knows exactly who we're talking about.

02:22:05.960 That's right.

02:22:06.360 Okay. So as long as you don't have a Hodad.

02:22:08.340 Yeah. You can, they can be reversed, but the reality is that.

02:22:10.980 What, 80%, 90%?

02:22:12.260 The patency is, yeah, I think it's over 90% for a, well, a good microvascular.

02:22:18.140 So if you're a guy who's deciding, who's sort of waffling on this, it seems to me that donating

02:22:23.860 a bunch of sperm, putting sperm into a, into a bank.

02:22:26.320 Yeah.

02:22:26.520 Having a really good person do the vasectomy is a surefire way to just go ahead.

02:22:31.140 Yeah. I mean, most of the time, you know, you can have, I mean, you know, the reproductive

02:22:35.080 technology is just ridiculous. So, you know, individuals who have Kleinfelters where they

02:22:40.640 really almost have no, no sperm production who are told 10 years ago, you can't have a

02:22:46.140 child. Now you can, you can do these procedures under the microscope where you can find individual

02:22:51.460 nest of sperm within the testicles of these men and you can allow them to have kids, which

02:22:55.960 is amazing for them.

02:22:56.780 I had no clue someone with Kleinfelters could do that. So, and then of course you're doing

02:23:00.980 it anyway because you want to be selective for, you know, making sure you're getting the right

02:23:04.060 chromosome.

02:23:04.420 Right. So, so I, I mean, I think there's nothing wrong with vasectomy. It's a very effective

02:23:08.940 way to do contraception. I think, you know, if you're single and you're dating around, I

02:23:14.140 think you should also use protection, not just contraception. So to me.

02:23:18.260 So this will be our public service announcement, not to be confused with the other

02:23:21.340 PSA. This will be the Schaefer PSA on wear a condom.

02:23:26.140 Yeah. I think not just for protecting or not having children, but for all the other reasons

02:23:31.120 to do it. Is there anything else that we can talk about in five minutes that's not going

02:23:36.240 to get one of us in trouble?

02:23:37.380 Well, there's lots of fun things that we, we can talk about like watches or pens or cars.

02:23:43.900 Yeah. You and I have shared that from the beginning.

02:23:46.300 Five minutes isn't going to work. It's not going to cut it.

02:23:48.300 All right. So on, on each of those, if someone could, if someone, you know, walked in the door

02:23:53.000 today and said, Ted, I'll, I'll, I'll buy you any watch you want, you know, within a reasonable

02:23:56.760 price frame, don't just pick the most expensive watch, but like, is there a watch you'd love to

02:24:00.600 just have sitting on your, on your desktop when you walk back into your office, courtesy of

02:24:05.940 some Santa Claus? I noticed you're wearing a beautiful Hulk today.

02:24:10.200 I do. I wear that on my non-clinical days. It's, I do like it. I didn't, I didn't wear

02:24:14.900 it a lot. I would say I'm look, I'm in the market. See, this is, I always just ask you,

02:24:19.120 I'm in the market for an elegant dress watch. I've never, I've never, that's the thing. I,

02:24:25.600 I have to say that, you know, I'm pretty satiated for watches these days. I'm good,

02:24:29.840 but I, I don't know. I want a elegant dress watch, but I could travel with it and it would

02:24:35.320 have GMT. That's my challenge to you.

02:24:37.360 Oh, for heaven's sakes. You had to throw the GMT.

02:24:39.900 Because I want to be able to wear a dress watch to a meeting and I want to be able to go to the

02:24:44.760 meeting, change my time zones. You know, I want to go to the meeting and not have nobody know what

02:24:49.540 the watch is. Right. Cause you know, yeah, I can get that in a Rolex or whatever, but it's, you know,

02:24:54.520 it's just sometimes it's nicer. I will take this on as a personal challenge. If you're willing to

02:24:59.480 give up the GMT, I'm really, I don't have it. I might never have it, but I'm really obsessed with

02:25:06.180 two Vacherons out there. One is the ultra thin and the other is the 1921, which is a remake of

02:25:11.560 the famous driving watch. Yeah. Those would be, but you know, you're not going to get a second

02:25:16.100 time zone on either of those. I just think, you know, you travel a lot too, right? It's so nice

02:25:20.420 to just know where you, what your time zone is at home. And that's what I like about that. I like

02:25:25.240 that. That's my newest thing. I love that. So I'm looking for a GMT watch because that to me is

02:25:31.660 like so important. So, so if you could get home to San Diego and find any car in your garage,

02:25:40.260 what would it be? Oh, it's a tough question. And I assume you mean a car that will only be driven

02:25:45.340 on the street is not going to be on the track. I'm not taking it to the track. This is for you

02:25:48.740 for, for, for San Diego. You know, you've definitely got me more and more interested in,

02:25:54.700 in Porsche. And I, I think that the nine 11 turbo, you know, so when that, I don't know,

02:25:59.460 let's just say I could, if I could get an early jump on a nine, nine, two nine 11 turbo, that,

02:26:03.860 that might be. Yeah. They're great vehicles. So well engineered. Yeah. They're, they're really

02:26:09.000 special cars and they're so drivable. I mean, there are other cars that I know you and I have

02:26:13.960 driven. We, we have friends who have beautiful cars that have given us their 488s and 458s and all

02:26:20.640 those things. And they're, they're incredible. I mean, I, I actually, I love the 458, but you just,

02:26:25.340 you're not going to drive that car every day. And there's something else that comes from it,

02:26:28.100 which is, is I guess I just deep down always feel a little self-conscious pulling or, you know,

02:26:33.740 driving around in the bright red Ferrari. And I don't think you feel self, you don't think you

02:26:38.620 just, you just don't have that same level of being self-conscious driving around in certain other

02:26:41.740 cars. But, but that said, you know, the 488 is a blast. See, I don't fit in it and I have a long

02:26:46.880 torso and I can't get the seat right. So I'm not looking at the head, you know, the head red,

02:26:51.200 the A pillar. Yeah. So, so, but it's a great, it's a great car and there are great cars out there,

02:26:56.980 but as a daily, you just can't, I mean, I, you know, that 911 turbos are pretty amazing.

02:27:03.120 Yeah. You know, I've never actually driven a McLaren. I don't know if you have.

02:27:06.660 I haven't, but I've heard those are really fun too.

02:27:08.880 Yeah. I, I, I have a couple of, uh, friends that have, that have them and they, I always have an

02:27:13.880 open invitation to go visit them and drive their McLarens in other cities. And those look like

02:27:18.260 really special cars, but you know, part of that's emotional too. I think I just have an emotional

02:27:21.600 connection to McLaren because of Senna.

02:27:22.980 Yeah. So I don't like the Senna though. I don't like the looks of that car.

02:27:27.000 Oh, I think that thing's going to be just a beast. I can't wait to see it perform.

02:27:30.160 It's a beast, but I mean, it just, it doesn't, you know, I like the functionality that they put

02:27:33.760 into their cars. Do you think that the Senna looks better or worse than the P1?

02:27:37.780 I think the P1 looks better, but I haven't seen either of them in real life. I've seen a 720 in

02:27:42.580 real life. It's a cool car. Really cool. The 720s look great. The aero in that car is cool.

02:27:47.260 I saw a P1 in person once in New York city of all places, which I've never understood

02:27:52.320 that logic. What would, what would possess you to, it wouldn't matter how much money you have,

02:27:56.540 what would possess you to drive a P1 in Manhattan?

02:28:00.200 Yeah. It's crazy.

02:28:01.060 It's like a Tom. I knew somebody who had a, had a LA, had a 918 and a P1. And he sold one of the

02:28:10.000 three because he said it just wasn't fun to drive around. Let me see if I can guess.

02:28:14.960 I don't know. Maybe the LA Ferrari?

02:28:16.320 The P1. He sold the P1.

02:28:17.840 Because it's just too much of a race car. So he said that you just, you know, on the,

02:28:22.580 he said on the track, it's just ridiculous. But he said that he sold it because on the streets,

02:28:28.300 it just, we couldn't even begin to enjoy it.

02:28:30.260 Wow.

02:28:30.800 It's so cool though.

02:28:31.580 I actually think all of those hyper cars, like I love watching Chris Harris take those cars

02:28:37.200 around. So for the listener, certainly the last generation of hyper cars were those three

02:28:42.980 cars, the Ferrari, LaFerrari, the Porsche 918 and the McLaren P1. Only one of them ever broke a

02:28:48.840 minute 30 on Laguna Seca. Do you know which one? I would guess the P1, but I don't know.

02:28:53.300 No, it was the 918 went one minute, 29 seconds, 0.89 seconds by 11, 100 service second. The P,

02:29:02.560 the 918 broke a minute 30 on Laguna Seca, the only production car to ever do so. Now my favorite

02:29:07.940 little tidbit. And I'll tell you, so which, so the 911 Turbo S is faster than a 918 at the ring.

02:29:14.960 I know. So, you know.

02:29:16.320 Unbelievable.

02:29:17.380 Right. Un-be-lie-ble.

02:29:20.200 But then of course there are $50,000 track cars that'll go a minute 19 on that Laguna Seca,

02:29:27.640 which again is the, always the great thing for people to understand the difference between

02:29:30.640 track cars and street cars. Yeah.

02:29:32.860 Ted, this was awesome. I know this was a bit more of a male centric episode, but I think

02:29:37.920 one, guys will get a lot out of this. But also I think, you know, for women who know a man who's

02:29:42.560 going through this or will go through this, I mean, I think there's a lot here. And we'll be

02:29:46.500 sure in the show notes to link to a ton of the stuff that was discussed. It would be great to be

02:29:51.380 able to link to any videos that you have on your surgeries. If people want to learn more about you,

02:29:57.020 I mean, obviously at Northwestern, the website will, you know, link to your bio, your CV and all

02:30:01.640 that other stuff.

02:30:02.140 Google Dr. Edward Schaefer. They'll get all the links, but NM or Northwesternmedicine.org

02:30:07.400 is a good way to find me. Dr-Schaefer.com is another way to find me.

02:30:12.720 Okay. Do you do anything on social media? Are you...

02:30:15.180 I'm... My handle is at Edward Schaefer.

02:30:17.360 Okay, cool.

02:30:18.880 Ted, this was awesome. Thank you for making the time and for your hospitality with insights.

02:30:24.220 Yeah. Thanks for having me, Peter.

02:30:27.700 You can find all of this information and more at peteratiamd.com forward slash podcast.

02:30:32.980 There you'll find the show notes, readings, and links related to this episode. You can also find

02:30:38.060 my blog at peteratiamd.com. Maybe the simplest thing to do is to sign up for my subjectively

02:30:43.320 non-lame once a week email where I'll update you on what I've been up to, the most interesting

02:30:47.800 papers I've read, and all things related to longevity, science, performance, sleep, etc.

02:30:52.580 On social, you can find me on Twitter, Instagram, and Facebook, all with the ID peteratiamd. But

02:30:59.080 usually Twitter is the best way to reach me to share your questions and comments.

02:31:02.660 Now for the obligatory disclaimer, this podcast is for general informational purposes only and

02:31:07.040 does not constitute the practice of medicine, nursing, or other professional healthcare services,

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The Peter Attia Drive - February 04, 2019

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

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