Science Cafe - Prostate Cancer - Biomarkers, Prevention Strategies, and Treatment Innovations

Science Cafe – Prostate Cancer – Biomarkers, Prevention Strategies, and Treatment Innovations

Join us for an episode of Science Café as we learn about prostate cancer diagnoses, treatments, and prevention strategies with Yair Lotan, M.D. Dr. Lotan is Professor of Urology, Chief of Urologic Oncology, and holder of the holder of the Jane and John Justin Distinguished Chair in Urology, in Honor of Claus G. Roehrborn, M.D., at UT Southwestern Medical Center. He is also the Medical Director of the Urology Clinic at UT Southwestern and Parkland Health and Hospital System.

Welcome to UT Southwestern Science Cafe. For our regulars, welcome back, and for our new guests, we are so proud to meet you this evening. My name is Charlotta Thompson and I am a part of the public affairs team at UT Southwestern. On behalf of my colleagues, Jenny King and Joya Elaine, as well as our guest speaker this evening, Dr. Yair Lotan, thank you for joining us tonight. Science Cafes are online conversations where our speakers take on deep dives into science topics. Our format is casual and interactive and we encourage you to ask questions and engage with us during the program. This evening, we'll be discussing Prostate Cancer: Biomarkers, Prevention Strategies, and Treatment Innovations with Dr. Lotan, more on him in just a moment. Before we begin, we'd like to mention a few technical matters. We are recording tonight's program and live streaming it on our UT Southwestern Twitter page. Please mute your microphones to help everyone's audio clarity and unmute if you are called on to ask a question. We encourage you to utilize the chat feature to list questions for Dr. Lotan. We will start Q&A at the conclusion of his presentation. Joya will facilitate Q&A and we are monitoring your questions in the chat box. Finally, just a reminder, while we cannot answer personal medical questions, we would love to hear from you with your general questions. With that, I'm pleased to introduce our presenter. Dr. Yair Lotan is a professor of urology, chief of urology oncology, and holder of the Helen J. and Robert S. Strauss professorship in urology at UT Southwestern Medical Center. He is also the medical director of the urology clinic at UT Southwestern and Parkland Health and Hospital System. Joya will add a link to his bio in the chat. Please click through and read all about his incredible work. Dr. Lotan, welcome to Science Cafe. The virtual platform is yours. Great, thank you so much. I think prostate cancer is a broad topic and one that I think a lot of people are interested in because it's most common cancer in men. I feel like I'm gonna touch the tip of the iceberg and hopefully highlight some areas that I think are interesting and hopefully will be informative for you. I want to note that the Simmons Cancer Center is a comprehensive environment where we collaborate between urology, which is my sub-specialty, along with medical oncology, radiation, oncology, pathology, radiology, and for cancer in general, it really takes a team. It's really rare for any cancer to be managed in isolation from anybody else. And so you really benefit from the fact that I have a great colleagues that I work with every day to try to find the best treatment for this disease. So what is the prostate? The prostate essentially is a gland that sits between the bladder and the penis and the urethra runs through it. And then main job is to help with fertility because of the fact that it makes secretions that help sperm stay viable. Unfortunately, after you finish wanting to have kids, it's only problematic. There are two different types of major problems that prostate causes, one, it grows with age and under the influence of testosterone, and when it gets bigger, it kinda compresses the urethra, makes it harder to urinate. That's not something I'm gonna talk about, but it affects about 1/3 of men over the age of 50. The other issue is prostate cancer and prostate cancer is unrelated to growth of the prostate, which is common as you age, but it is associated with both testosterone's genetics, but the two problems are not necessarily connected one to the other. So it's the most common life-threatening cancer in all of men, but almost 250,000 men a year are diagnosed with prostate cancer. And even though you hear that prostate cancer is slow growing and doesn't kill a lot of people, it's still the second most common killer among men, about 34,000 men a year die of prostate cancer, second only to lung cancer. So it is still a serious disease and can lead to death and quite a large number of men. And unlike men with enlarged prostates, most men with prostate cancer usually don't have symptoms until the disease spreads. And that's really the main reason why we screen for prostate cancer. We want to catch it before it's causing problems and while it's still localized to the prostate when we can most effectively cure you. So what are the risk factors? By far, the strongest risk factor is hereditary association. If you have a first degree relative, a father or brother who has it, you you're a risk doubles. If you have two first degree relatives, the risks can be as high as five to 10, 11 times higher. So certainly, I think this is maybe not what you talk about over Thanksgiving dinner, but I do think it's important to talk to your male relatives to know whether or not they have prostate cancer. And also important that if you have prostate cancer, you tell your sons about it and you tell your brothers about it because they'd be an increased risk. Unfortunately, African-American men, men from the Caribbean are at higher risk for prostate cancer than white Caucasian people. The higher age you are, the higher the prevalence of disease and the Western diet, high-fat diet increases the risk. So we know that the Mediterranean diet is protected from a variety of cancers and it seems that the diet high in fat, high in protein may increase your risk for prostate cancer. Unfortunately, there've been a variety of supplements that have been tested for a while, people looked at vitamins that are antioxidants, selenium, things like that, but none of them has been found to reduce the risk for prostate cancer so far. This is just highlighting the issue related to race and ethnicity. You can see that African-American men have almost twice a higher risk than white people, significantly higher than Asians. And unfortunately, mortality rates are also higher, more than double the rates. So in particular, it's important for those men to get screened at a younger age and to know their family history. How do we screen for prostate cancer? Well, the most common test is a PSA test, which is a blood test that looks for factors that are secreted only by the prostate and prostate cancer cells. It's highly sensitive in the sense that if you have a normal PSA, your risk of having prostate cancer is quite low. But it's not very specific, and what that means is that if your PSA is elevated, there are other causes of elevated PSA. You can have enlarged prostate, you can have inflammation, you can infection, you can have trauma, but you can also have prostate cancer. And this is problematic because you can't really tell for sure when the PSA is elevated what the cause of elevation is and that means that you end up doing a lot of biopsies even though many of those patients may not have cancer. Well, what's the benefit of doing PSA testing? One, it's a blood test, so it's not particularly invasive to get it, but it does cause some pain. The biggest risk though, is over-diagnosis. So what does that mean? If you find prostate cancer that wasn't going to kill you, then it's not great to have that diagnosis. I mean, if you're 80 and you're gonna likely die of a heart attack in the next three to five years, you don't wanna know if you have prostate cancer, which may not tell you for 10 to 15 years. And we also know that there's some patients who have low grade cancers that don't need treatment at all. And we'll talk to you about active surveillance as strategies. But I think if you knew you had a small amount of low grade cancer that wouldn't kill you, you'd rather not know it even existed because that means you wouldn't have to have followups and et cetera. The other risk of PSA, as I mentioned, is that you might get a biopsy, but you just have inflammation, and biopsies they're not fun. They cause some discomfort that can cause some bleeding, they can cause a risk for infection. So we don't want to do biopsies if we don't have to, but sometimes it's unavoidable. What are the benefits of PSA screening? Well, you might find cancer early, you may allow for early treatment and insurance usually covers it. It might give you a peace of mind if it's normal that you don't have prostate cancer and there's some value to that. So what do we do if you have an elevated PSA? We'll recommend a biopsy of the prostate and that basically means we're going to take tissue samples from the prostate with a small needle. Sometimes, we'll use MRI and there are some additional blood tests that we use and sometimes, if the PSA is just borderline, we'll just repeat it. So what does MRI do? Well, when we just biopsy the prostate without an MRI, we just targeting the prostate, but we don't know where the cancer is because ultrasounds also the cancer very well. But we've been using a lot of MRI and when use a multiparametric MRI, which basically means that you have a lot of different cuts of the prostate, you can suddenly see areas of abnormality that are more likely to be cancer. And this particular patient, you have this area here that's dark when the rest of the prostates are bright and on a different type of parameter, you can see that it's dark when the rest of the prostate is lighter color. And then you say, okay, this looks like it could be suspicious. And then you can direct your biopsy to that area rather than just taking samples of the prostate not knowing where you're aiming. And this pictorial kind of illustrates the fact that if you have a cancer in the prostate with a very dark area representing a more aggressive cancer and the lighter area representing a less aggressive cancer, you can see that if you do a random biopsy, you might miss a cancer altogether. You might just hit part of the cancer that's not aggressive and only using a directed biopsy to go to the middle where you get it through sampling and see that the patient has a more aggressive disease. Now, sometimes you can have a patient with a very small nodule that might even be difficult to target with an ultrasound, even with MRI overlay. And so we have radiologists here who can actually, while you're getting an MRI, actually aim and target specifically for these small nodules. This is called an inboard biopsy, and it's done with anesthesia because it's all uncomfortable to have it done under MRI guidance. But in patients who have small but suspicious areas or patients who have had prior biopsies, sometimes we utilize it just so we can get a correct diagnosis. Now, once we find out you have prostate cancer, the next most important thing to find out is how aggressive is your cancer. And there are basically two different scoring systems that we use and what pathologist will get, will be get a piece of tissue and they'll look at the piece of tissue and they go, okay, here, there's very few cells, here, there's more cells, this is the cancer area. And then they also look at this part, let's say, and then they say, okay, there's cancer here. And they look at the two most common areas of cancer and they give them each a grade from one to five. And it turns out that it's confusing now because one and two Gleason scores aren't even considered cancer, but then you add the two areas together and if you find that a patient has a two areas with a three, you have a total of six, which now is great group one, you thought this wasn't confusing, but this makes a low grade cancer. Then you have a couple of different areas of intermediate grade cancer, which are sevens. And then you have eight through 10, which is high grade cancer. And this is what we use along with what your MRI and your PSA shows to judge how aggressive your cancer is and what kind of treatment you should get. So we now usually use what we call a risk adjusted treatment modality. So if you're a low risk, you have a Gleason score of six, your cancer is confined, your PSA is low, and these are patients who are good candidates for either active surveillance or local therapy. For patients with intermediate risk cancer, now they have Gleason six, but maybe they have a little more disease or a little higher PSA or they have Gleason seven, we usually do a local therapy. And for those with more aggressive disease, we started looking at surgery, novel therapies, or radiation with hormone therapy. So we're worried more about these patients and these are the patients most likely to die of prostate cancer, those with high risk disease upfront. So what's the benefit of active surveillance? We used to about 10 years ago, to say, “You have prostate cancer, you're gonna get treatment.” But we know that all our treatments have side effects and so people started saying, “Well, what if somebody just has a very small amount of low grade cancer? Do they really need treatment and why don't we just watch them and periodically evaluate them and decide if they do in fact have cancer growth and then treat them only then? So the benefits of active surveillance are that you can reduce complications, improve quality of life for men, avoid over-treatment, and in general, there's less anxiety because of a tumor doesn't require treatment and it's not life-threatening. You can reassure patients that they don't need to worry about it. And of course, if you don't have to do expensive treatments, you save money. Now, I listed this at the bottom because that's not really our main goal, to save money, but improving quality of life, avoiding complications, that's really our primary goal in treating patients. So what's the downside? Well, there is a risk that the cancer will grow and progress, so that can cause anxiety. You can be concerned that their cancer might progress and that you might miss an opportunity for a cure. And there are some risk of having multiple biopsies affecting sexual function or causing anxiety. Generally speaking, our evaluation is meant to avoid missing an opportunity to cure patients. So how do we do that? Well, we get a PSA, we check that every six months, we'll examine you periodically. And then most people will do an MRI every couple of years to make sure that there's no signs of cancers growing. We usually will do a biopsy, usually in the first one to two years to make sure that we've been missing any areas that are more aggressive. And then if your cancer gets worse, then we treat you. And so how well does that work? Well, this is just a number of the active surveillance series that are out there and they vary in the number of patients, but I wanna highlight the cancer specific survival. And this basically means what the chance of surviving your cancer is. So almost all of them are 100%, 100%, 99.9%, 98% at 10 years, 94% of 15 years, 99%, 96%, 99%. So almost nobody is dying of prostate cancer when they are on appropriate active surveillance. And that's reassuring, it basically means that when we pick you for active surveillance because you have a small amount of low grade cancer, we can almost always keep you from dying of prostate cancer over a time period. Does that mean nobody gets treatment? No. In almost all these theory series about 1/3 of men, maybe a little bit higher percentage, ended up needing treatment. But you do avoid treatment in the rest of the men and some of these are pretty much older series before people using MRI. And so we're doing a little bit better job of selecting patients. And so the number of patients requiring treatment has gone down over the years. What about treatment? Well, obviously, we treat a large number of men. We probably remove about 500 prostates a year at UT Southwestern for men with more aggressive disease. This is the da Vinci robot, which is how more than 95% of all prostates are moving nowadays. The surgeon actually sits at the console and then the robot is attached to the patient, and the surgeon is manipulating these arms, which are placed through very small incisions in the patient's body. The other options of treatment are focal therapy, which I'm going to discuss, and radiation therapy. I think, as I mentioned, all the treatments affect sexual function and urinary function, and so if we can avoid them, that's the best thing. And we do have ways with both surgery and radiation to try to reduce the risk of issues with urinary and sexual function. Now, as far as the da Vinci system, the nice thing about it is three dimensional view, it gives you a lot of precision, the robot doesn't get tired, and there's a little bit more comfort than sitting next to the patient. It's usually about two to three hour surgery and patients usually spend one night in the hospital. What about radiation therapy? The main issue with radiation therapy is how do we cure you and reduce the impact on quality of life? And so when you look at quality of life issues for men who have prostate cancer and need treatment, you think about issues related to their bowels because the rectum is near the prostate. You think about sexual function, you think about continence, you don't want men to leak, you think about irritation to the urinary tract. And so the goal with radiation is to try to precisely radiate the prostate and not the areas around the prostate. So for example, here's the prostate, here's the bladder, here's the rectum, and so you want to use MRI, CT scans to try to target better. You want to be able to try to give focal therapies in terms of not giving the radiation to spread too far away from the prostate. You can do that sometimes with breakthrough therapy, just putting seeds directly into the prostate. In UT Southwestern, we've started more than 10 years ago, what's called stereotactic radiation therapy. And the goal of stereotactic radiation therapy is to give only five treatments compared to the 40 that have historically been used and to really try to get the dose primarily at the prostate. Now, as I mentioned, one of the issues is the rectum is nearby. So we've started injecting a hydro gel between the prostate and the rectum, and that gives you a margin of error where you can radiate the prostate without affecting the rectum, which is right below it. Here are some schematics of a patient who is getting treatment with stereotactic radiation therapy. Here's the prostate, here are the hip bones, here's the spacer between that and the rectum. This is a side view. Again, here, you're looking at the bladder, and the goal is to focus the radiation highly in red at the prostate and have lower doses to all the surrounding structures. And so this is something that the radiation oncologists here are specializing in and really trying to focus on how to reduce complications related to this radiation therapy. Now they also have a novel trial that they're working on, where they're trying to preserve the neurovascular bundles, which is where the nerves that control sexual function run. So here's a patient with prostate cancer. There's a prostate, here's the spacer between the prostate and the rectum, and here's the neurovascular bundle carrying the nerves that control sexual function, and here they're targeting the radiation to avoid this area specifically, so that reduce the chance for nerve damage. And so this is a trial called POTEN-C that Dr. Desai is spearheading. Now, what about focal therapy? We've all heard about the fact that women who have breast cancer get a lumpectomy, they don't have removal of the entire breast. The problem is that you can't just cut part of the prostate because of the fact that the urethra runs through it. So you can't remove surgically just part of the prostate. But if you have a small tumor here, why not just treat that tumor and avoid the rest of the prostate and hopefully avoid those nerves that go to control sexual function, avoid the rectum. And so we've started doing a focal therapy approach called TULSA, where we can heat specifically one area of the prostate using MRI guidance. And so this TULSA-PRO technique is basically an acronym for transurethral ultrasound ablation of the prostate. And you basically have a probe in the prostate that has a heating element, you have a device in the rectum to cool the rectum so the rectum doesn't get injured, and you do MRI so that you can target where you do the heating. So this is a little video schematic, patient goes under anesthesia. Here's their prostate and the bladder and we put the probe into the urethra, we get an MRI to take very discrete images of the prostate, and then we identify the area that we wanna heat. And then basically the device in the urethra rotates and specifically heats the part of the prostate that you're interested in heating as you're monitoring it in real time. This schematic is treating the whole prostate, but if we wanna do focal therapy, we literally would just treat one quadrant and not treat the whole thing. And this is something that we started doing last October and we treat about four or five minimums currently. And you can see down here as MRI's going, we literally can watch the area heat, make sure that the rectum is getting heated, that the heat isn't going outside of the area where we're interested in. So this is an example of a patient who had a area heated. So this is the MRI before and this is the MRI after, and you can see, we precisely heated this part of the prostate, the rest of the prostate is okay. The neurovascular bundles, which are sitting right here are unaffected on both sides. This is the rectum. There's no area impacted between the rectum and the prostate. So this was a trial that was actually done. We were part of the original trial and 115 men, they got it FDA approved. These were men, typical men aged 45 to 80 with a grade group one and two disease. The whole prostate was treated, so the PSA actually went down by about 95%. The prostate volume also went from 37 to three, so over 90% decrease in prostate volume. The caveat though, is that when he biopsied most men, only about 65% had no cancer. So in men with a grade group two disease, 80% had no grade group two at one year and the majority had only mild to moderate side effects that went away within the first three months. So it's not perfect, but this was not focal therapy. These were men who had multiple areas of the prostate and the whole prostate was treated. So this is something that I do always in conjunction with a radiologist. So two main radiologists who are doing it right now are Dr. Costa and Dr. Diaz de Leon, and there's multiple urologists who are currently doing it myself, Dr. Meng, Dr. Goldberg, Dr. Gahan, among others. So take home points for me are that prostate health and prostate cancer care are really better now than they've ever been. Screening is crucial for this, especially in men at elevated risk, African-American men, and men with a family history. PSA testing is still the best bet at early detection. And just because he had prostate cancer doesn't mean you need surgery or radiation, but obviously, it depends on the grade of disease and your PSA. And there are new options to improve the quality of life with treatment. I want to acknowledge some people who provided some slides. My chairman, Dr. Roehrborn, who treats a lot of men with prostate cancer, Dr. Desai, radiation oncology, and Dr. Costa in radiology. And I think we had quite a few questions, so I'm more than happy to answer them. Dr. Lotan, thank you. We really appreciate your insight this evening. Before we jump into Q&A, I'd like to add in one celebratory remark. UT Southwestern is nationally ranked by U.S. News & World Report among the nation's top 20 hospitals for urology. So congratulations to you, Dr. Lotan and to your team on this tremendous achievement. Now for audience questions, as he mentioned, we got quite a few. So I'm gonna dive right in. The first question, any guidance for primary care providers regarding screening, diagnosis, when to refer, et cetera? Sure. So PSA has been controversial, and there has been sometimes when The U.S. Preventive Services Task Force, which gives grades to certain screening and testing, has given PSA sort of marginal grades. And that has actually impacted the number of people who get screening, which is not in my opinion, a favorable thing, the American Cancer Society and American Urological Association, both recommend screening. Generally speaking, I think the issue with screening that has always plagued the testing has been the fact that we, in the past, used to treat a lot of men who probably didn't need to be treated and giving the screening a bad name, because the thought is, you're gonna just find a lot of cancers, you're going to treat men who don't need treatment, you're gonna do a lot of biopsies. Generally speaking, I think that PSA testing, overall, I think is informative. And for myself, I get a yearly PSA, and exam, and that's kind of recommended for people with a family history or who are African-American starting at age 45 and extending to about age 70 is a recommendation. But really, I tend to recommend it until people have about 10 to 15 year life expectancy. So some people are very, very healthy at 70 and you might consider continuing it, and some people are very unhealthy at 65 and you may consider stopping it. As far as the referral, I think the answer is if somebody has a rising PSA, if their PSA's over four, or if it's a young person with a family history whose PSA went from two to two and a half to three, which is higher than you would expect in somebody in their 40s or early 50s. As a urologist, I'm always happy to see patients and discuss the pros and cons of biopsy. Obviously, if they don't get referred or don't get a PSA, then there's no opportunity to even have that discussion. Next question, why is the biopsy done blind? Shouldn't an MRI or sonogram be done first looking for specific sites to biopsy? So biopsy's never done blind. All biopsies are done under ultrasound guidance so that we can see the prostate. So there's an ultrasound probe that we put in the rectum. And then the first thing we do is actually numb the area around the prostate so that it's not as uncomfortable. And then we look at the prostate with ultrasound. The problem is that the ultrasound is very good at seeing the prostate, but it's not great at seeing small tumors. And the truth is that the vast majority of men that we biopsy nowadays will have had an MRI beforehand and then we can do what we call a fusion biopsy, which is to overlay the images of the MRI onto the ultrasound in real time so that we can target areas of suspicion. It is also true that in some men with borderline PSAs, if we do an MRI and it's completely normal, we might avoid the biopsy because if we don't see any suspicious lesions on MRI, the chance of missing cancer is probably 10% or less. So unless they have very, very high PSAs, we might just say, okay, let's just watch and see if there's a trend with your PSA so that we can maybe avoid some of the unnecessary biopsies. Thank you. I'm gonna jump to the chat. Our first question comes from Janice. Can you compare radiation to proton therapy and can proton therapy also treat lymph nodes? Yeah, first of all, proton therapy is radiation therapy. We often get questions about proton therapy and I have to say that I'm a little biased against proton therapy in the sense that proton therapy was designed to treat tumors in the brain and the spinal cord. If you look at the hype around proton therapy, is it stops at a dime, and that's actually very good if you're in the brain and right next to a tumor is normal brain tissue because the brain doesn't move because it's encased by your skull, but your prostate is not encased by anything, and so your prostate moves every time you breathe, it moves up and down, your rectum pushes it forward and backwards, as your bladder fills, it goes up and down, things like that. So stopping on a dime is not a meaningful thing for the prostate. And so for me, they'd been doing proton therapy for more than 20 years at Loma Linda, and nobody's ever demonstrated any benefits to proton therapy over standard radiation therapy. It's just a very expensive way to deliver radiation therapy. Any radiation therapy can be given both to the prostate and to the lymph nodes nearby. You can radiate any part of the body to be perfectly honest, if you can image it. And so frequently for men with higher risk cancer, we do radiate not only the prostate, but also the lymph nodes in the pelvis just to make sure that if they're involved, that you're able to hopefully kill the cancer there. Next question from Bill, other than the Mediterranean diet, are there any other preventative measures that can be taken to avoid prostate problems? And I'm gonna add to that any other, I don't even want to say diets because I don't prefer that term, but I'd say food groups or vitamins to fill up on. Sure. The long and short is that nothing has been demonstrated to be beneficial. Now, we've been doing a study for the last four or five years, looking at curcumin, which is a compound that comes from turmeric, which is a root, and curcumin is actually on a lot of shelves at GNC and Whole Foods, et cetera. The problem with curcumin itself though, is it doesn't get absorbed well. So most of the studies that have been done with curcumin are actually in colon related diseases because it just goes straight through your intestine to your colon. We're actually studying a compound called bio curcumin that unfortunately you cannot get commercially and gets absorbed about five to seven times more than regular curcumin. And we're studying it in a trial compared to placebo on active surveillance and men who've had their prostate removed. Now the problem is I'm blinded. I don't know the results of the study, and it's going to take several more years to finish it. And until then, I can't really recommend it. In fact, you can't even get it. So I'm not recommending people take curcumin and turmeric. The rest of the supplements, unfortunately, I told you, there was a study in 32,000 men looking at selenium and vitamin E. Neither of those showed a benefit. They were trying to do a study with lycopenes, which was sort of a hot supplement. It's an antioxidant, if you have in tomato and ketchup, but they couldn't do a trial because imagine which half of the group would want to be the one that's not allowed to eat salsa, ketchup, tomatoes, pasta for six or 12 months to find out if they were the control group so that the other group could take the lycopene. So they could never do that type of study. So in general, I don't really recommend it. I mean, I find that it's a multi-billion dollar industry because people are spending billions of dollars on supplements and they're not regulated by the FDA. So you don't actually even know you're getting what you think you're getting when you buy stuff off the shelf. So to me, it seems like a waste of money. I just tell people, eat a hard, healthy diet, eat fruits and vegetables, you'll get all the vitamins and supplements you need that way. Thank you. I am going to launch one of your poll questions right now, Dr. Lotan, just to see who is in the audience. So I'm gonna give it maybe 30 seconds and if everyone could just vote, does everyone see it on their screen? Yes. This is great. Is it on the screen? It is, it's on mine. They're still coming in. I do not see it on my screen. When I ended, I'm gonna share it. I just wanted to give everyone a little bit of time to as long as it takes. Okay, we have 61, that's enough. Let me share the results. So 33% are patients, one caregiver, 23% are healthcare providers, and the majority are just someone looking to learn more. That's great. Awesome. Dr. Lotan, can you stop sharing your screen and then we can see everyone? Excellent, thank you. I'm gonna go back to the chat for our questions. From James, would you comment about evaluating DNA from Seminole fluid to screen for stages of breast cancer? I'm sorry, prostate cancer. Yeah, so there's actually a variety of genetic tests currently out there. Some of them are looking at seminal fluid, some of them are looking at what we call methylation changes, which are changes that happen in cancer and DNA. Some of them are looking at RNA, which alterations within the cancer itself. Many of these are trying to predict whether or not your cancer is going to be more aggressive or less aggressive. Some of them are trying to figure out are you likely to have missed cancer? The problem with most of these genetic tests beyond the fact that they're very expensive is I haven't found them to be good enough right now to make a dramatic change in my treatment recommendations. So for example, if you're a patient with a small amount of low grade cancer and they wanna look at genetic tests, then how they are they doing that? They're gonna look at that very small piece of tissue that you've got and look for genetic abnormalities in that small piece of tissue. And then you say, “Okay, well, this is a patient who, let's say they have a 1% chance of cancer spread, even if you double that risk, it goes to 2%, what does that tell you? Does that tell you that if you didn't want treatment at 1%, even with 100% improvement in prediction is 2% gonna make you wanna do something. What about if it cuts it in half, now you're half a percent? So even a marker that changes prediction, and none of them are that good, none of them are 100% better than what we already know. They might be 10 or 20% better. And so if it's not gonna change what you end up doing, then I don't think it's a worthwhile tests. And so if I'm gonna order a test on somebody, I actually will ask them, what will we see on this test that will make us change our mind about what we're going to do? Because if you can't convince me that you're gonna change your decision on what you're going to do based on a test, then I think it's a waste of time and money for you. And that's kind of where most of these tests are for me right now that they're not going to change management. I'm gonna jump back to some of our pre-submitted questions. What is the optimal PSA number? Zero. (presenter laughing) I mean, if you had prostate cancer, for sure is zero or less than 0.05. I mean, if I could have a PSA of zero, I would take it now with my prostate. I don't ever wanna have a high PSA. So I mean, it's an excellent question, but lower is better. Got it, how low can you go? Okay, next question. Do you see immune therapies such as immune checkpoint inhibitors becoming more widespread in the treatment of prostate cancer? Well, they're not heavily utilized now and that's because there aren't really studies that show compelling benefit from a survival standpoint for them. Right now, most of the treatments are related to lowering testosterone or impacting what we call the androgen receptor, which is the receptor on the cell, which testosterone interacts with. And so quite a few of the treatments really are related to manipulating that hormonal access for prostate cancer. The immune system really hasn't and these checkpoint inhibitors haven't really been found a place yet. There's still a variety of clinical trials looking at it, but so far they haven't really played a significant role. Thank you. Our next question comes from Daniel. With the advancement of radiation techniques, what are the common side effects now or how many patients who undergo radiation would later need followup surgery? Well, I mean, that's an excellent question in the sense that I would love to be able to answer it generically, but it's very much based on what cancer you started with, how aggressive it was. I mean, surgery and radiation have very similar effectiveness. Overall, there's some slightly higher rate of late recurrences with radiation than with surgery. The problem with patients who have radiation is that the urethra is impacted, the bladder is impacted, the rectum is impacted, things kinda get stuck to each other. And so it's a much higher risk if you go and do surgery after radiation that you will have incontinence, you will have sexual problems, you might have rectal injuries. And so we almost never operate on people who have had prior radiation. Now, interestingly, we're starting to look at doing, maybe this TULSA procedure on patients had prior radiation 'cause we can then hopefully target the area with the cancer in it and we can heat this sat area specifically and hopefully, avoid injury to the rectum, maybe avoid incontinence and other things that happen if you do surgery. But surgery after radiation is not common. Radiation after surgery though is much more common because of the fact that you can radiate the area where the prostate was if there were a few cells that had escaped the prostate, it's much safer to do radiation and has far less impact than the reverse. Thank you. I never knew that's why radiation typically comes after surgery. Next question comes from Dorian. How does biotin affect PSA test results? Yeah, it can sometimes cause it to go up. Generally speaking, I don't necessarily tell people not to take it or to change what they're doing. I don't even always know that they're taking it when they're getting their PSA. I suppose, if you had an elevated PSA and you're on it, you could stop it for a week or two and then get a PSA done. It usually doesn't change it so dramatically, where it's gonna altered what your decision-making is or what you're doing in regards to the patient. But if somebody had a borderline PSA before you did a biopsy, I would repeat it off of it. Thank you. Next question comes from Wen Hong. You highlighted the utility of MRI and prostate diagnosis yet with limitations. From the perspective of imaging technology development, what improvement would you wish to have in prostate MRI or ultrasound, especially in the area of contrast agent development? Well, I mean, when you look at an MRI, they have a PI-RADS scale and the PI-RADS's scale goes from one to five, and one to two are very low risk of prostate cancer, and that's great. And five is almost always prostate cancer more than 80% of the time. And that's terrible, but we at least know what to do. But PI-RADS three, which is in the middle, is indeterminant. So it's no greater or lesser chance of having prostate cancer, which is usually about 1/3 of those men have prostate cancer. And PI-RADS four sort of moderately suspicious, and those about 50 to 60% of men. Now, what we really want is to be able to improve in that three and four category. So we have a more definitive answer. If we can get the threes that are suspicious, we wanna be able to biopsy them. If we get the four that are not suspicious, we might be able to order the three that are not suspicious, avoid a biopsy in them. So that's really what we need better precision in these indeterminant categories. And it's interesting, people are doing studies with PET scans now, PSMA scanning, which is prostates membrane antigen, which is maybe more specific for the prostate, got approved by the FDA. It's not been approved for diagnosis, but hopefully, some of these newer technologies will improve our precision. And there are several trials that are going on and we'll probably be opening a trial as well trying to evaluate that for improving staging. You just mentioned PSMA and it correlates perfectly with Martin's question. Could you explain it just a bit more and why have it done? Well, you can't have a done yet, but there are a couple of centers in the country that got approval from the FDA to use these agents. But basically, cells have antigens on the surface and PSMA is an antigen that's specifically on prostate cells. And the way PET scans work is that you would take an isotope, which is, think of like a fancy Geiger counter, and you would link it to something. So a lot of PET scans that people are used to are linked to sugar, for example, because when you look at cells where are active, like cancer cells, they're using a lot of sugar. And so if you link an isotope to sugar, then you'll go to the areas of increased activity in the body and that will lead you to places like cancer. But that's not specific. I mean, the brain uses a lot of sugar, these substances get excreted by the kidneys, so those things light up. Now the PSMA hopefully, will go specifically to places where you have prostate cells. Now if it's inside the prostate, that's one thing. But if it's outside the prostate, that's obviously concerning and can help you know that somebody's disease has spread. Also, there are people who are looking to add therapeutic agents to these things. So if you can link it to something that will kill the cell, and if it only goes to prostate cancer cells and kills them, then that actually could be a therapy to use in men with more advanced disease. So people are very interested in using this characteristic of this antigen that specifically on prostate, both to improve staging, but also maybe to use it as a treatment. Thank you. Next question from Angela. Once the cancer has spread, what's the best treatment? Well, generally speaking, as I mentioned, we usually do hormonal therapies. The main one is to lower your testosterone because testosterone is the main fuel for prostate growth. If you lower the testosterone, there was a scientists won a Nobel prize for that more than 50 years ago. It dramatically decreases the growth rate of prostate cancer. Unfortunately, it's not curative, but it will slow it down for many years. There are other drugs though that affect the ability of other androgens that are made by your adrenal glands from getting into cells or from keeping the cancers themselves from making their own hormones. So there's a variety of different hormonal manipulations that we use to treat men with disease spread. We also use chemotherapy and some other agents, but typically, the most common treatment is hormone therapy. I'm gonna jump back to some questions submitted ahead of time. People in underserved areas may not have the opportunity to have tests available. What would be the best way to monitor prostate? Well, PSA testing has been available anywhere in this country for many, many years. So really that's the primary way to diagnose and monitor prostate health in general. So I would say there are many areas of health disparity, but that's not really one of them. We all have access to PSA in every community level in the US and probably worldwide. What varies is how often primary care physicians use PSA, whether or not they believe in it and what they do with it if your PSA is elevated. And often we'll tell patients, “Look, you know what your cholesterol level is, or at least many people do, know what your PSA level is.” And so many men don't even know if their PSA is being checked, they don't know what the level is so then they have a hard time knowing if it's elevated. And so I'll see men and they'll have a PSA of four, 4.2, and I go, “What was it last for?” They have no idea, they even hadn't done in the last year, last five years, last 10 years. And so I think since it's the most common cancer in men, it seems reasonable that men would keep track of what that test result is. And if they're not getting it and they're interested in getting screened, they need to ask their doctor to get it done. Thank you. Given the slow growth of prostate cancers, when would treatment be indicated of an asymptomatic nonmetastatic patient? All right. First of all, as I mentioned to you, we want to catch it when it's asymptomatic and non-metastatic. In fact, it will almost never be symptomatic until it's metastatic or it's growing where it's blocking your urethra and you can't pee. But most of those men actually don't have prostate cancer, just have enlarged prostate. Generally speaking, for men who don't have small volume, low grade cancers, we recommend treatment unless they have a short life expectancy. Now, the treatment lies mentioned could vary from focal therapy if they have a small confined tumor to surgery, radiation, hormones, or a combination of those. So a lot of it really depends on what the grade is and how aggressive the cancer is. But that really is the main guide for us on whether or not you need treatment or just monitoring. It's generally fairly straightforward how aggressive your cancer is based on your PSA and the grade of your cancer. Thank you. Next question comes from Robert. With robotic-assisted prostatectomy, is the internal urinary sphincter generally spared? So there are two sphincters. There's tissue where the bladder and the prostate are connected. That's usually what we've considered your internal sphincter, which is the involuntary one. It's what keeps men from leaking when they're walking around, because your bladder neck is closed, and that is cut during surgery, so it is not spared. You have an external sphincter, which sits below the prostate, which is what we're trying to preserve and what you have to do kegel exercises after surgery for. That is the voluntary sphincter, and anybody, men and women, both have voluntary urinary sphincters. And the next time you go urinate, if you want to try to stop your stream, it's a bit uncomfortable, but that's your sphincter contracting. And anytime you're watching a movie and you're waiting to see if the bad guy gets shot and you're kind of holding it, that's your voluntary sphincter contracting. In fact, sometimes it's hard to go urinate afterwards 'cause you have to relax your voluntary external sphincter and your involuntary internal sphincter in order to empty your bladder. But no, we cannot preserve the muscle fibers between the bladder and the prostate because those are injured when we cut the prostate out. Thank you. Robert asks does having robotic surgery enhance the risk of having a hernia later? Anytime somebody makes an incision in your body, you enhance your risk of having a hernia. Hernia is basically an opening in the fascia of your abdominal wall, and during surgery, robotic surgery, we make like five or six of those small holes. Most of them are so small. We don't have to close them, but we do close the one where we remove the prostate out of, we put that in the bag and we take it out. But yes, theoretically, anytime somebody makes an incision, they do increase your risk for a hernia. I'm gonna take a few more questions. Why is it fasting considered a precursor for surgery? Wait, say that again? Why isn't fasting considered as precursor to surgery? Fasting. I mean, we tell you not the right before you get anesthesia. That's a rule. When you say it's not a precursor, it is a precursor in the sense that if you eat, you're not getting surgery, unless you have a car accident, we have to do it emergently. No, they usually tell people to fast usually eight hours or something before surgery. So you say, we tell people, “Don't eat after midnight or something like that.” Great, thank you for clearing that up because that was a question submitted ahead of time. Let's see. Could you explain the importance of calcium injections and at what stage they're given? Calcium. Urologists don't do calcium injections. I'm not sure who does calcium injections. In men who are getting hormone therapy, we recommend taking calcium supplementation along with vitamin D to reduce the risk of osteoporosis. There are some drugs in men or patients with osteoporosis that help promote bone growth that are given to reduce the bone breakdown in men with metastatic disease. That's given by oncologists. I think that's all I'm gonna speak to that because I'm gonna run out of information. But no, we don't give calcium injections. Another myth that you have proven wrong. Thank you. I'm gonna launch another poll before we start to wrap things up. This is an important one. Men, are you getting a PSA test routinely? Okay, I'm gonna end it and share the results. So 84%, yes. That's pretty good. I mean, some men might be over the age of 70 and it's not necessarily recommended, or if you're under the age of 40, it's not recommended, but it seems like a pretty responsible audience. I think so. One last question from Carl, are there other ablation techniques or technologies that compete or are as effective as TULSA? As effective is tricky because none of these companies do head to head trials. They don't wanna find out that they may not be as effective. So they're not doing anything else. There are a lot of different modalities for focal therapy. There is something called IRE, which is irreversible electroporation, which basically you put several probes in the prostate and if you turn on the electricity between them, it kind of fries to some extent the tissue between. I say that, but maybe what it does is actually creates holes in cells so those cells die. The benefit of it is that it preserves the architecture. So it's thought maybe not to have as much damage on any nerve structures nearby. There's cryotherapy that's been used for many years to freeze tissue. Don't forget that the TULAS-PRO is basically just a way of heating tissue. So you can use high frequency ultrasound to heat tissue just like use a microwave to heat issue. People have used lasers to ablate tissue. Sometimes people have just put in a few radiation seeds in one area to radiate tissue. So they're probably six or seven different ways to do focal therapy. The nice thing and the reason we pick the TULSA-PRO is that we liked the fact that you can do MRI monitoring. Most of the men, we diagnose are with MRI. So we know where the cancer is and we want to be able to heat relatively, precisely that area. And we feel like that's a good melding of our current technologies. But we're gonna start a trial of this IRE later on this year. So we're gonna even ourselves have several different technologies that we're gonna have available for focal therapy. I look forward to learning about how those trials go. So we might have to schedule a follow-up in a year or so. Thank you so much, Dr. Lotan. I'm gonna turn it over to Charlie. Thank you, Dr. Lotan. It was fascinating to learn about your urology studies and the latest trial results. I, for one, was really impacted from learning how important PSA testing is on a consistent basis. Thank you to Joya and Jenny for helping run tonight's event. And for our audience, we hope you'll join us next month for two very exciting episodes. In two weeks on October 7th, we'll have our next Science Cafe episode, getting to know UT Southwestern's, if then, ambassadors. And then on October 21st, we'll hear from another speaker from the UT Southwestern Simmons Cancer Center, Dr. Asal Rahimi, who will give us a special presentation on breast cancer treatments and the latest radiation oncology research, just in time for Breast Cancer Awareness Month. So please be sure to register for both events. Joya will paste the registration links and the COVID link in chats right now. Before we adjourn, we must implore you and your friends and family to get a COVID vaccine. Vaccines protect you from severe illness and deaths from COVID-19 and its variants. See the chat for one more link, a UT Southwestern presentation that was presented yesterday morning about COVID. The playback is on YouTube. For more information, including vaccine appointments, click on the yellow COVID info bar at utsmed.org. And finally, even if you are fully vaccinated, please continue to wear your masks, social distance, and be vigilant with hand hygiene. Thank you for doing your part to contribute to our collective public health. And for now, we wish you all good health, good spirits, and a good rest of your evening. We are adjourned.

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