In this episode, Dr. Slavin welcomes Dr. Todd Cohen, Vice President of Medical Affairs for the Myriad Urology department. Dr. Cohen formerly practiced with Hawes Urology before pursuing an academic role as the Assistant Chairman of Urology at Ohio State University. He then co-founded Piedmont Urology in Charlotte, NC before forming Carolina Urology Partners, a merging of nine urology groups, where he acted as co-CEO, then CEO. Myriad Genetics welcomed Dr. Cohen in his leadership role in March of 2019. Dr. Cohen brings his many years of expertise to the discussion regarding genomics, the role of gene expression assays, and the treatment of prostate cancer.
0:00:11.2 Dr. Thomas Slavin: I am Dr. Thomas Slavin, senior vice president of medical affairs for Myriad Oncology. Welcome to Inside the Genome.
0:00:18.7 DS: Hi everyone, welcome to the podcast. Today we have Dr. Todd Cohen, he is the vice president of medical affairs for our urology unit at Myriad. Welcome to the podcast, Dr. Cohen.
0:00:30.6 Dr. Todd Cohen: TJ, thanks so much for having me. It's a pleasure to be here.
0:00:33.5 DS: Yeah, if you wouldn't mind giving the audience a little bit of background about yourself, how you came to be in this position, your training, that would be, I think, really useful just to ground everyone.
0:00:43.7 DC: Sure. Well, I trained in urology at the Cleveland Clinic about 300 years ago. I think I finished in 1995. And then from there, did a fellowship at Duke in... At the time, it was in minimally invasive surgery. From there, went on into practice. Began my career in academic medicine, actually, at the Ohio State University, where I was the assistant chairman for a few years.
0:01:09.3 DS: Is it the Ohio State University? [chuckle]
0:01:10.0 DC: And then, for various reasons... The Ohio State University. Actually, my office overlooked the horseshoe, so if I stayed there late on a Saturday, which I tried not to do too often, I could look right into the stadium.
0:01:24.2 DS: Oh wow.
0:01:24.6 DC: So it was kind of a great position. How I ended up with that office being like a junior-level guy was beyond me, but I did. I stayed just a few years there. It was more for family reasons, and we relocated to the Charlotte, North Carolina area, where I began a private practice with a group. And then as time went on, after some seven years in practice, I helped form a larger group called Carolina Urology Partners. With them, I was their founder and CEO for about eight years. Until a couple of years ago, I decided that I had done a lot with the practice and was in clinical practice as well as running the practice for a long time, and just decided it was time to slow down from that. So rather than just go back into clinical practice, the opportunity came up to work with Myriad, and I jumped at the opportunity. A lot of it because I'd been working with them for a long time with my own practice with various testing, and I was really enamored by how the whole field of urology was heading, and that was really the impetus for me to make the move. And I thought I could do a lot of good for a lot of people on a national level. Although I felt fulfilled locally, I thought I could really expand on that, and that was the big reason for my move.
0:02:43.9 DS: Yeah, no, great. And yeah, we're certainly lucky to have you, and that's why we wanted to bring you on today because you are... At this point, with your recent job move over the last few years and your interest in genetics, and exactly what you're talking about, your passion to drive this into routine urology care, I wanted to get your perspective on the way genomics is moving into urology, medical oncology, of taking care of men with prostate cancer or other urology conditions. And so yeah, thank you so much for coming on.
0:03:15.8 DS: So to start, first, there's many different areas that genomics is creeping into routine urology care. I was thinking, one of the initial ways was gene expression assays. I don't know if you wanted to just talk a little bit about what a gene expression assay is, how can you use these things in taking care of men with prostate cancer in particular, and where you see them going in general.
0:03:40.9 DC: Yeah, sure. Probably back in the early 2010, so somewhere 2012, 2013, we saw the introduction of these genomic assays, the gene expression assays, as you were talking about. And they've really made a difference and what was lacking was the ability to really adequately risk-stratify patients. What we've been holding onto for so long was, in urology especially, really just clinical pathologic features is how we would separate and try to figure out how to best treat a patient or what their risks were, given certain treatment options. And what we've relied on, really, since the early 1980s, is just a prostate exam, a TSA determination and what their pathology look like under the microscope. And as we learn more and more, there's not only is there problems with this, it's just not enough. There's a lot of subjectivity, especially with the exam. PSA is pretty objective, it doesn't vary much. But your Gleason determination by pathology, even in the best hands, vary greatly.
0:04:50.2 DS: We should probably talk about what Gleason scoring is, maybe real quick, just for our general audience.
0:04:55.3 DC: Okay, yeah. Gleason scoring was developed by Dr. Gleason from Stanford, who just categorized what prostate cancer looks like under the microscope. And really, in easy terms, the more different the glands looked in a normal prostate, they were given numbers. So if the glands looked like you didn't even know they were prostate, if you didn't know it came from the prostate, then they'd be a five. And as it got closer, looking like normal prostate, those numbers dropped down and the ones were not really even cancer, and people don't even consider a two a cancer anymore. So really, the scoring system came out to a three, four or a five, where the five was terrible and the three was cancer.
0:05:40.5 DC: And then you take the two most common patterns of these, what they see, and add them together, and you get a Gleason score. So the score kinda ranged from a six to a 10, where 10 is terrible, and a six is, some people are considered not even bad. The problem was, one guy can look at this under the microscope and say, "This is a six." And then you ship it off to two other people, and one guy may say it's a seven, and one guy might even say it's an eight. It's really goes from a six to a 10 or something, but it can happen. So there is a lot of subjectivity, and this is what we're relying on to decide how we treat patients.
0:06:16.9 DC: So out of this really kind of arose the genomics, the gene expression classifiers, to be able to better risk stratify and see, is this patient more aggressive or aren't they. And if they are more aggressive, should we treat them more aggressively? And if they're not, would this patient be a candidate for even watching it? Or some... 'Cause a lot of the cancers, a lot of prostate cancers, they're just not lethal, but who's who, when we had trouble determining that just by taking them out. This really... That idea of watching somebody, which we call active surveillance in urology, really was the beginning of this. It was, we need something better.
0:06:52.3 DS: Yeah, you need a better tool. Prostate cancer's so common.
0:06:55.8 DC: Absolutely.
0:06:56.0 DS: You can't just [chuckle] take every single man on the planet's prostate out.
0:07:00.8 DC: Right, exactly. It's not in a good place to just, "I'll just have your prostate out and see how you do." It's just not amenable to that.
0:07:08.1 DS: Yeah, and how are these now used in clinical practice? Are they now becoming just routinely used throughout?
0:07:14.9 DC: Yeah, yeah. I would say it's still gaining steam. A lot of people are still relying on their clinical pathologic because they've been used to that and comfortable and they say, "Well, I don't know if I need it." But what they're realizing is that the times are changing, and they're not really judging how their patients do based on anything more than, "I think my patients are doing well." There's really not a lot of, in the community setting anyway, a lot of data that people can hang their hats on. I think people are realizing that there's more precise treatments. There's better treatments than there were, and we can really guide a patient onto the path of what's best for them as we head towards the kind of over-used term, but we use it and it's probably correct, is personalized or precision-based medicine. And these are really helping us get the patients on track to do that, so to get more precise treatment specifically for them. And I think these are the tools that are really helping us guide that, and doctors are more and more understanding that as they go on.
0:08:22.1 DS: Yeah. Do you have to use one or the other? Is it clinical features or these gene expression assays or is there something else?
0:08:29.4 DC: Yeah, well, generally, the best way to look at these is to combine them. We know that there's good prognostic ability to see how people are gonna do from their treatment based on their clinical and pathologic features. Most of these assays and the ones that I'm most familiar with, combine these together and give you the power of combining the known clinical stuff with the expression classifiers, the genomic expression classifiers, really makes it even better. So you're not excluding this, and as I like to say, we're not going to say people, "You've been using this for 30, 40 years. We're not saying your baby's ugly. We're saying we can make your baby even better."
0:09:10.4 DS: Yeah, absolutely. As people become more familiar with genomics, it seems to also be leading to genomic increase in hereditary and then cancer therapy. Thinking about hereditary, how have you seen hereditary risk for prostate cancer change over the last few years in particular?
0:09:28.4 DC: There's just really an explosion in that information lately. It used to be that when a man would come in, he'd be diagnosed with prostate cancer, he'd say, "What should I tell my family?" And in the past, the only thing we could tell him is that, "Well, your sons are at higher risk of prostate cancer," and that's where it ended. Now, we found, over the last several years, that there are a lot of genes that are inherited, the germline genes. Just like in breast cancer, these genes can really make a difference as to, not only are your family members at risk and you can pass this down, but your own cancers can be definitely changed to the degree of how aggressive they may be or how they'll respond to medications in the future can be determined by the genes that are present within the whole body or that are present in the cancer in particular.
0:10:17.3 DC: Urologists are 15 to 20 years behind the other oncologists that are specializing in things like breast cancer or ovarian cancer, maybe even colon cancer. We're just understanding the implications of these. The uptake is gradual because we're still trying to figure this out, but people are seeing it's absolutely necessary and how important it is and how it ties back to breast cancer as well.
0:10:40.5 DS: Yeah. Well, better late than never. And then I saw, too, [chuckle] recent emerging data about that, yeah, certain gene mutations, if you have an inherited mutation, those gentlemen aren't even great candidates for active surveillance because there is a concern that they could go over to a more aggressive type of prostate cancer quicker, like men with BRCA2 mutations.
0:11:02.9 DC: Right, yeah, especially BRCA2. In fact, most of the guidelines talk about if a person has the BRCA2 mutation, which is the breast cancer gene, or considered to be the breast cancer gene, 'cause we haven't claimed it to be able to call it the prostate cancer gene yet, but these men are at much higher risk of developing significant disease, dying from disease, developing metastasis. And it's profound enough that the guidelines are starting to say, "If you have a guy that has this, regardless of how aggressive their cancer may look now, these are guys you may wanna reconsider for active surveillance or keep an extremely close eye on them compared to your other guys that don't have these mutations."
0:11:45.3 DS: Yeah, no, agreed. And this is a odd segue then to the next phase, which is now therapy treatment for men, and I say odd in the sense that who had thought that germline [chuckle] mutations would then play into therapies, but now we clearly know that PARP inhibitor therapeutics and pathways are really, really important in taking care of individuals with all kinds of cancers, and prostate is appearing no different. And so there's been some recent trials that have taken place that have shown, yes, that men with problems with BRCA1 and 2 that are inherited or that developed in their tumor, as well as other genes that hang out in that same pathway, are very good candidates for PARP inhibitor therapy. I was just wondering your thoughts on all of this and where you see this going.
0:12:34.9 DC: Yeah, you're hitting on it exactly. Again, for personalized medicine or precision, you wanna target what may be driving that cancer. And there's a lot of different therapeutics in prostate cancer. When you get to a certain point, some of them just don't work anymore. And what we found, what you're describing is a couple of studies that have shown that the drugs, the PARP inhibitors in certain men that have mutations present, where the mutations that they are born with or mutations that they acquired in their lifetime, certain drugs like the PARP inhibitors will be beneficial to them. And we're learning more and more of how we can identify men that will respond, and detecting these mutations is the absolute key at the beginning, at least.
0:13:19.2 DC: I think what's leading more towards this is just the understanding of if men have a problem of mutation in the certain genes, they will respond to certain treatments better or even at all. And I think this is what we're heading towards, is certain treatments will work for men and certain treatments won't, and can we find why that they'll respond and then can we tailor treatment based on what we detect for each individual man and give the best chance for cure or prolong their lives?
0:13:52.4 DS: Yeah, it's really exciting to see all the...
0:13:54.3 DC: Yeah. It's fascinating what's happened.
0:13:56.1 DS: And it's moving very rapidly. And then I also think of people that are born or have mutations in genes that have to do with mismatch repair deficiency, and recently how much action that's been providing around immunotherapy. So yeah, whether inherited or in the cancer itself, there's many genes that we've been well familiar with for a long time that do seem like they make a massive difference for therapy.
0:14:23.0 DC: Yeah. What's exciting is that rather than just identifying them and say, "Yeah, you have a mutation," and you pat them on the head and say, "Have a nice life," you can actually do something with that information. And to be able to take that information and act on it and really help somebody is such an accomplishment. In urology, it's the first time ever that we've had what they call a companion diagnostic or a test that says, "If you are positive, you are a candidate for a certain treatment." Urologists are not used to that. This is... In no other aspect of our treatment of any kind of cancer in urology do we have this until now. And the doctors are starting to understand this better.
0:15:04.8 DC: And so as far as implementing the testing and moving this forward, there's a lot that needs to be done. The guys that are in the forefront in treating, especially advanced prostate cancer, they have a good understanding of this. The problem is those guys are few. And what we're doing and what's needed is a broad education, and a general understanding of genetics and how it can change the treatment from what we talked about earlier, not being a good candidate for something like active surveillance all the way up through if they're advanced, what's the best treatment for this guy based on their genetic profile.
0:15:47.2 DC: And so I like to say, the average urologist is old. The average urologist is my age, about 57. And we sit back and we go, "Genetics? Yeah, I remember genetics. Yeah, that's... Your pea pod is either gonna grow a [0:16:00.0] ____ tall or it's gonna be short depending on the genes. And well, that's what I remember about genetics." So this is all very new and can be a little bit challenging for the guys that are spending 60 hours a week just taking care of patients. It requires a good broad level of education, which is really something that we, especially at Myriad, are focusing on. Just very important to get out there and get men to understand the need for these types of tests and how they can really affect new treatments.
0:16:28.3 DS: Yeah. Do you see any big grassroots educational efforts going on right now by any of the societies or anything in this regard?
0:16:34.9 DC: I think the societies are calling for need for education, and they're relying on some of the training programs to do it earlier in resident education. And I think a lot of it is being done by not necessarily the academic society as much 'cause they're concerned with, for the most part, with the education of the residents, but for the guys that are out there, they're partnering with industry like ours and some other societies that are more clinically based to get the word out. And it's really picked up steam. I think there's more needed. Time is always an issue. Especially in this world of COVID, it's hard to get large groups of people to do the large groups of mass education. So a lot of it is gonna be done virtually or web-based, so the guys can go back and at their time, whatever time's good for them is look at it, and try to do it in a timeframe where guys can do it without being overwhelmed. You put a three-hour class together, it's very difficult for people to sit through that, but several 15-minute increments, tying things together really seems to be what's working best.
0:17:45.0 DS: Yeah, absolutely.
0:17:45.5 DC: And we're really trying to work on that kind of timeframe.
0:17:48.3 DS: Yeah, no, that's great. Well, it's, like we said, a fast-moving field equals need for [chuckle] education and little time to do it. And there's a lot of studies going on. We just kinda touched on the surface of all the different things going on and there's a huge iceberg below that. So yeah, very complex. Well, I just wanna say thank you so much, Dr. Cohen, for coming on the podcast, sharing your insights around prostate cancer, urology. I really appreciate it, and love working with you and look forward to many years to come where we can co-drive genomics into healthcare.
0:18:26.5 DC: You couldn't have said it any better. I feel the same way, and it's great working with you and the collaborations. And being able to push this forward with you has just been... It's been a dream of mine now, and it'll carry me through the rest of my career, and then I'll hand it all off to you and some younger guy later on.
0:18:43.3 DS: No problem.
0:18:45.8 DC: Thanks again.
0:18:46.3 DS: Thank you again.
0:18:46.8 DC: Thanks for having me.