Evidence Behind Prostate Cancer Treatments
PCF Chief Medical Officer Dr. Phillip Koo leads a conversation with urologists Dr. Michael Bivins (Urology Centers of Alabama) and Dr. Benjamin Lowentritt (Chesapeake Urology).
Learn how physicians consider the scientific research – clinical trials and real world evidence – behind every treatment plan, and how they discuss this with their patients. Drs. Bivins and Lowentritt describe how it’s important to first establish trust and understand a patient’s personal goals and expectations for treatment.
They discuss examples of how evidence helps guide common decision points in prostate cancer:
- Choosing between prostatectomy and radiation therapy
- Understanding when focal therapy may be appropriate
- How therapies such as androgen receptor pathway inhibitors (ARPIs) and sipuleucel-T may be used in advanced prostate cancer
Finally, the panel covers how you can learn more about getting involved in research – whether a clinical trial or registry study – and what to ask your doctor.
PCF thanks Dendreon for their support of this program.
View Transcript:
Phillip Koo, MD [00:00:00] You know, before coming to this webinar, I actually had the privilege of attending an event where I was able to listen to the story of a woman who lost her husband to metastatic colon cancer, colorectal cancer, when he was diagnosed at the age of 44. Such a heartbreaking story, but unfortunately, it’s a story that we hear all too common. And you know, I sort of walked away with many ideas rolling through my head, but it sort of reinforced two things.
Number one, we really need to continue investing in research to find cures or just different ways to control all the different types of cancer. The good news is what we see is that money spent on research does make a difference. You know, clearly in prostate cancer we have so many new drugs available for treatment. You know, when we think about pancreatic cancer, which you know is terrible, we had that great news that was presented at ASCO this year regarding overall survival, which increased, doubled, pretty much doubled. So, I think these stories about research leading to better treatments is real. I think we just need to continue focusing on that.
And number two, we need to focus on this patient empowerment and patient education. And it’s a great way just to sort of feel more comfortable having those discussions and making sure every I is dotted when you’re going through that journey. This topic in particular I think is so timely and I think it’s gonna be so impactful. And I really appreciate Becky when we were discussing this for coming up with this idea because it’s something that we all think about, but we just don’t quite understand how these decisions or suggestions are made.
You know, we talk a lot about patient-centered care, shared decision-making, but what does that really mean and what are doctors thinking when they try to put all this together. And that’s what we’re gonna try to do today, is we’re going to try to get into the minds of the physicians who are taking care of these prostate cancer patients and figure out how best to sort of make that discussion most efficient and figure how we collectively can do what’s best for the patient. So, thank you Mike and Ben for joining us today and we’re just gonna go right into it.
So, you know, when we think about all the different things you’re balancing. You’re thinking about clinical judgment, you’re thinking about the scientific evidence, you’re thinking about guidelines that are published, and there are multiple guidelines that have sometimes the same, sometimes different recommendations. And then you’re also balancing patient preferences and their desires into discussions. Just sort of walk us through what’s going through your mind when you go into that initial visit, and you are giving recommendations on what treatments to pursue next. So let me start with you, Ben.
Benjamin Lowentritt, MD, FACS [00:02:51] No, thank you. And thanks so much for having me. And I’m excited. Thank you to all that are attending. You know, I think what’s one of the most interesting things and specifically around prostate cancer is that so often we have a lot of options and so it truly is, you know in my mind, I mean shared decision-making is this concept where we say, okay you’re not walking into the office anymore and the doctor’s telling you what to do. And that’s a two-way street, right? So, you have to have a patient who’s willing to engage and ask the right questions and express what they want. But you also have to a doctor willing to hear that and work with somebody to do that. And I think that’s not always the immediate dynamic. So, I do think a lot of this at first is just sort of getting that comfort of expressing yourself. And once again, it’s both sides, right? I think as a doctor, we get used to our routine kind of discussions, but it’s never routine for the patient. And therefore, it really is never routine for the doctor because there’s always that individual aspect of it as well. So, I think whether you always appreciate that these things are happening, I think they’re happening on both sides of the conversation to some extent. Um, and now with that being said, like, I think there’s some standard things that we try to get across, you know, to everyone in a discussion, which is what are the options, you know, what are the potential, you know, benefits of anything? What is it? What are we trying to achieve? And then what are the downsides of it? I mean, I think that’s a very simplistic kind of way to look at it, but it’s always at the core of everything. And, you know, trying to figure out where those benefits often come from our ability to distill a lot of different information and studies and things that have come over past decades into the current day, depending on the situation that you’re in and what you’re talking about. So, I do think. What we consider efficacy tends to be the dominant thing that we talk about as physicians, like what is the upside? What is the best thing that we can expect to get from this or the typical thing that we can except to get from a treatment? Whereas I think oftentimes for patients that’s an important thing, but we also have to realize the other circumstances that are impacting that. And I think it’s just important to develop that conversation to be able to talk through it.
Phillip Koo, MD [00:05:25] Great. So, you know, it’s interesting when I talk to some patients, they come in and they say, you know Doc, I don’t want any chance of erectile dysfunction. So, they’re willing to take on perhaps more risk because they don’t that potential complication. There are other times where they’ll say, hey, Doc, what would you do if this was you? So, Mike. I’m sure you’ve heard those, you know, those extremes. There’s lots to balance. Sometimes the evidence is very clear. Sometimes it isn’t. So how do you sort of balance all that with the patient preferences to give your final recommendation?
Michael Bivins, MD [00:06:06] Yeah, so the first thing, and I’ve been in practice 24 years, so I’ve sort of kind of changed my approach overall. I think trying to just give that human experience, right? How am I beyond just a computer and AI? Just how do we engage there? And, you know, I’ll tell you just dealing with a lot of advanced cancer patients is I make sure I don’t try to buttonhole anybody into anything. And then the first thing I want to do is establish goals. Okay, what are the goals? And it used to be I would just set these clear goals. I want to get you to 100. And then I realized, hey, that’s me setting a goal for a patient. And I’m like, okay, let me sit with you and let’s try to define the goals. Is that do you want a lot? Do you want life? Do you wanna live? Do you want quality of life? You know, so once we can establish in things that they can attach, you know, how many more, you know, marriages and graduations do you want to go to? You know all those things and once we can cross that barrier where we’re having that human experience, right?
Then we start to talk about the disease. Then we started to talk about the options. Then we start to talk about expectations. And then as you start to peel those onions back, you’ll get to those issues. And along the way, you establish trust. And so that when I have those real conversations, and I’ll tell people, and let somebody comes in, because I can only deal with what’s in front of me. And I will tell people you’re gonna have some changes, right? You’re gonna to have those things, like you’re going to have changes where your erections and your sexual experience is gonna be different after whatever treatment, likely than it was before. You may have to do some things different, but you’re still gonna have, we’ve already established quality of life, but you’re still gonna to have quality of your life, because you’ve removed that fear out of the conversation. So that now we can have these scientific portions of the discussion, and which include, okay, here are the options here, here’s what you expect from an efficacy standpoint, here’s, what you’d expect from outcome standpoint, here are some of the potential side effects, and here are options that we have that can mitigate some of those things. So, it’s a little bit of a, on the forefront, establishing trust, establishing this human connection so that we can get to those scientific parts. But I tell people, in particular I’m a surgeon, but if you have surgery there will be changes. The way you are engaging in that sexual experience maybe now is going to be different, potentially. But you’re still able to have that experience. You may have to do some things different. You may take some shots. You may have to take some pills, but you still can have a good quality of life.
Phillip Koo, MD [00:09:04] You know, that’s great. And I think, you know, the discussion about having your goals upfront, and that sort of then frames the discussion moving forward, I think is a really good piece of advice. So, I encourage patients and their loved ones and their caregivers to really have that discussion about what your goals are in these different scenarios. So, let’s, you know, I’m going to come back to you, Mike, about AI because I think that’s a very interesting topic. But let’s go back to the evidence, because really, when you make decisions, it really is rooted in, as you mentioned Mike, efficacy, making sure that these drugs or these treatments have been proven to be beneficial for patients. So, Ben, let me talk to you and ask you about clinical trials. Sort of walk us through why they matter, what information you sort of glean from that, and how that influences how you manage and take care of these patients.
Benjamin Lowentritt, MD, FACS [00:10:00] Yeah, so I mean, clinical trials that we know about, right, or that we talk about are generally how these therapies are proven to work in a way that we feel confident using them. And in many ways, because of the way that drugs are approved, they’re the trials that lead to a drug being approved for a certain condition in a certain timeframe, right? Something like prostate cancer has many different phases and a therapy may work in one phase but not really be all that relevant for another phase. So, it’s not like it’s just a simple discussion all the way through and clinical trials in in in those kind of key approval processes are generally what we would say are prospective meaning that there’s a whole set of goals that start out and you have to prove it throughout to get to an endpoint that you know makes sure that it works and it’s doing what we want. And then helps guide us to say, okay, how well did it work? And what is the overall benefit? And then also it looks at what are the risks? And it generally does that by comparing to a group of people that get the treatment versus a group that don’t, right? And that’s those trials that lead to, the big trials generally that lead to approvals, and I think understanding what the goal of the trial was and then did it show its goal or not. I mean, these are all key points that help us determine kind of the relative value of one therapy over another or kind of help us shift from one whole type of therapy into a new type of therapy because, hey, they were compared in a clinical trial. Generally, you’re comparing some new treatment to what is the existing standard of care. So, you know, this is how we get new standards of care that we can offer widespread to patients. And so, there are a number of them. They’re always happening. And we’ve been fortunate, all of us on this have been fortunate to be part of some of these trials. Many, many, many trials happen that don’t show a benefit. So, when you start to see those trials that really do show a benefits, it’s very impactful in what we can offered to patients, so. Um, you know, there’s a lot of work and a lot of time that goes into it. And a lot of patients, thankfully that participate because, you know, going into it, you never know truly what’s going to work and what’s not. I mean, we all have our, our healthy, uh, you know, expectations, but it’s a real significant process to get to that point. Uh, and so once we have those results, it’s really critical for those results to be shared, which is, you know, through things like PCF and UroToday. And a bunch of meetings and all those things, but then to the patients as well. And oftentimes the doctors are the key educators in that respect of kind of what’s out there. And so, it’s important for us to be up on that.
Phillip Koo, MD [00:13:07] Shifting gears a little bit, when should patients ask about being perhaps a patient in a clinical trial?
Benjamin Lowentritt, MD, FACS [00:13:18] So I think there are often trials available, depending on the setting, you may be in a site that does or does not participate in a clinical trial. There are many resources online to find clinical trials near you, but it’s sometimes hard for the patient to understand if they fit into an exact criteria that a trial is being done for, because very often, they’re very specific questions and very specific populations of people that are being asked. But I don’t think you should ever be afraid to ask your doctor. Are there any trials available in this? I think we always it’s always essentially number one on our option because in almost every case it’s the standard of care plus something additional that’s being evaluated So we try to you know, especially in cancer. We’re not withholding care from anyone at this point you know so in most in most of these types of trials, so I think it’s a healthy part of the discussion to ask at any stage. There also are you know a number of resources where you can search by geography to understand if there’s trials near you um you know and really by any of the special things that might be special about your disease as far as previous treatments or you know genetic changes or anything that you might know about yourself
Phillip Koo, MD [00:14:37] I think that’s a great key takeaway that I’m gonna just reinforce. Clinical trials, don’t be afraid and ask about them at any stage, whether you’re just diagnosed, recurrent, advanced, after second line, first line, second line third line therapy, it’s always an option and ask. And there are resources online as well, which we’ll also have a resource soon to help with that process. So, Mike, I’m going to ask you this question. Oftentimes patients will come into your office and be like, You know, I did my own research, or I did research or I read about research. And this is a question that actually came in through our Q&A, talking about ivermectin or some other treatments or someone asked about Emsella Chairs, which I don’t know what they are and you could fill us in on that. But how do you sort of have that conversation when patients have done some reading about this, but perhaps the sources or maybe the validity or the quality of the research may not be at the level of these clinical trials, which we know are very, very controlled?
Michael Bivins, MD [00:15:42] Yeah, I mean, excuse me. Everybody has this thing called a phone, and they’re able to do research right at their fingertips. Or excuse me, they’re able to look information up. And the first thing I try to tell people that every source or resource is not a great source or resource, and you have to look at the source and where it’s obtained. And I never try to put people down, and particularly if someone has taken the interest in their own care to go research and get knowledgeable about their disease and about treatment options. You know, I definitely make sure that I want to ensure that they understand what is standard of care. What are the clinical trials available. What has been tested in a safe environment. What’s been FDA approved. Understand what is the FDA? Why it’s there? And again, you still have big trust issues. When I hear people ask me about natural supplements or natural options. And I don’t discredit, disprove unless they’re potentially something that’s harmful. And maybe we adjunct and take a supplement and add it to whatever standard of care. But I have to make sure as their agent that I am leading them, and I am conducting in such a way that I’m guiding them in the right direction with the right care. And so, if there is something that is brought in that’s not potentially harmful, and you know, let’s look at it and let’s research it together. And, you know I always have my phone, I always my AI agents ready, let’s look it up. Sometimes I’ll learn something. Well number one, I may learn something in that experience but certainly a lot of times patients will also. And so, I don’t discourage people looking up information. I don’t discourage agents that potentially aren’t harmful, but I don’t substitute for standard of care options. I think it is a fine rope you have to it takes some skill to learn how to walk but I encourage patients to be involved in their decision process to do research and then they may be able to teach me something, but I always try to make sure we come back to what is standard of care? Where is the truth? What and where is FDA approved data that we can utilize to help patients?
Phillip Koo, MD [00:18:37] I think that’s great advice. Patients, make sure you disclose any of these other treatments that you might be taking because it’s very, very important. And if you don’t feel comfortable, that’s why, Mike, I love your response of you’re not judging them, you’re not just dismissing it. And if you feel like you aren’t comfortable sharing that information with your physician, that’s something that you have to reconcile because it is absolutely critical. A question came in about trials and how do we know it’s not doing any harm or there’s something else. If it is better, what happens? Rest assured, the beauty of clinical trials is there’s a whole process to these. They have to be monitored and if there is signal that the treatment arm is better than the standard arm, they may stop the trial and switch patients to that drug or they may actually cross over during the trial. So, there are mechanisms in place to make sure patients aren’t missing out on something, you know, by participating in a trial. So, you know, I think it’s wonderful how advanced and how trials have developed in the U.S. and globally over the past year. So, Ben, we’re gonna shift the conversation a little bit. So clinical trials are great. They have very specific inclusion and exclusion criteria. And we know that in the real world, patients don’t fit into these molds the way they have to for a clinical trial. So, there’s something called real-world data and real-world evidence. And I know you’ve done a lot of work in this space. Kind of give the listeners out here, the viewers, sort of what is RWD [real world data] and what is RWE [real world evidence] and why is it important especially moving forward?
Benjamin Lowentritt, MD, FACS [00:20:26] Yeah, no, and this concept of real-world evidence, the way that I think about it and I try to explain it is that we’ve seen a lot of shifting over the years of what information is available for what’s actually happening in a regular doctor’s office, not in a clinical trial, right? So… And a lot of that has come from the fact that you now, when you walk into your doctor’s office, almost every doctor is sitting there with a computer or a laptop and is entering all of your information into the computer. So now there’s actually a place other than a paper, you know, chart that may have really bad handwriting in it where it’s accessible information. And not all of it is easily deciphered even through that kind of, you know through a computer, but this is where there is power in big numbers, right? You know, a clinical trial may have a few hundred patients needed to prove a point, right, a prospective randomized, the kind of clinical trial we were talking about before. Real-world evidence might be able to pull from thousands and thousands of different patients and therefore can answer questions that we’re unlikely ever to get a true clinical trial able to answer. So, maybe it’s a particular subtype of patient and how they respond to a treatment. Maybe it’s looking at two different treatments and, hey, is there actually one that works a little better than the other? Or maybe is it, you know, is there some sort of trend that we’re not able to pick up because clinical trials are very, very structured and designed to a specific question and a specific endpoint. So, You know this concept of real-world evidence isn’t new just because we have computers there have long been studies that are sometimes have been called registry trials or you know chart review trials and they tended to be very much focused on a specific group that was able to pull together that information or maybe a specific point in time and you know getting patients enrolled. Um, and current real-world evidence often is able to pull from these, you know, thousands and thousands of additional treatments too. So, it is not, um, they’re actually, you know, a lot of ways to make real-world evidence as rigorous as possible. Uh, cause of course, what you don’t want is a situation where someone kind of seeks out to prove a point and then just finds the charts to, you know, the, the historical charts to then prove their own point, right, and prove a bias. But there’s structured trials now that very similarly to clinical trials can help us answer questions without having to go, you know, the ability to go through a clinical trial that may take years to sort of set up and then find. We may be able to look back with real-world evidence and at least get strong indications that some details may be true or not true.
Phillip Koo, MD [00:23:32] You know, through registries or RWE studies, often new information or new side effects might come to light. And I know there was a question submitted about, you know, abiraterone and neuropathy in the feet or something like that. Can you give us some examples of where something like that might have occurred that was, oh, wow, we didn’t know that in the trial, but clearly in the real world, maybe, you know we are seeing some adverse events.
Benjamin Lowentritt, MD, FACS [00:23:58] Yeah, well, I think that we do get these kind of notices every now and then that said, hey, you know, there’s a signal about, you know, patients getting we didn’t think they would get seizures with this medicine, but oh, yes, now we’re seeing that there’s seizures, you know, with certain medicines, and it may only be in, you know, two tenths of 1% of patients. So, we just happened to not get that patient in the trial. You know, there are, and so those things have sort of come to light, you like that, there are circumstances where there’s been interactions between two medications that, you know, maybe one of the medicines is relatively new and we didn’t have it when it was tested the first time. And so now you get, uh evidence that, geez, these, these combinations don’t seem to do as well. You know, I think, I don’t know, Michael, if you have any other examples or anything, but I don’t think- there’s almost no limit to what you can try to find in real-world evidence. But there are limits into what some of the conclusions you can get to. So, I think we’re always trying to be cautious in what we glean from real-world evidence, but at the same time, this is where, and you mentioned AI briefly earlier, but this is where we’re going to continue to learn a lot of things because there’s so much information now that’s at our disposal.
Phillip Koo, MD [00:25:19] I think that’s a great, you know, takeaway message there as well, you know, RWD, RWE is great. I love, you know, the drug-drug interaction type of thing will come up. And, uh, but you know we do need to proceed with caution. So just because they say this doesn’t mean it’s true because in the end, still clinical trials are our best and most controlled research type of activities. Uh, Mike. You had an interesting story about AI. Clearly, AI is becoming a part of so many different parts of our lives, very important tool. In healthcare, it is actually a good tool. And can you talk us about sort of your experience with a patient bringing AI to your attention?
Michael Bivins, MD [00:26:00] All right, I didn’t recognize this was a physician. To be honest with you, we were in a sit-down consult, and we were going through a process. It was an advanced cancer patient, and the patient had his AI open. And as he was talking, he was going through his phone, and he was answering or asking questions. And if I’m being honest, I felt like I was one leg. I was a little bit slow in that sort of interaction. And then I realized he had an open AI program going. So, at that moment, I’m like, let us both learn here. Let us both share. What do you have open? But I think we see that now. I think that whether that’s Claude or Chat GPT, patients are utilizing this, they want to know what their options are. They know what the data is. They’re trying to see how they can fit in there, how they fit in the data, how the data fits them in their situation. And it was very dynamic. And, you know, at first, I felt maybe a little bit sort of threatened by it, but now I just embrace it. And I’ve had conversations where we both had AI programs going at the same time, because I want to know what’s going on in the world real-time. And these AI programs can scan fast and maybe. Am I saying the right thing? Am I hitting the drug-to-drug interactions, for example? I don’t know all of them, very fast, very quick, and you can know it right then and there. And if I’m writing a particular ARPI on a patient and it’s a particular drug, and I think a patient had a particular side effect and I wasn’t sure about it, and they were on two drugs, and I was able to kind of figure out which drug might have been causing that particular adverse event. So, I think we were able to get to the situation or get to a resolution much faster. And I remember a patient bringing in a particular adverse event and I didn’t know about it and they showed me an AI because they had looked it up. And so. I think we all got better. We all better, I mean, it’s here. It can analyze a lot faster than anybody on this call tonight. And so, I think it’s a great tool for both the patient and the doctor. And so, and I think is gonna get better. Last thing is, I’m using Heidi [an AI medical scribe program]. I don’t know if Ben uses Heidi or Phillip, you use Heidi, but they have an AI program built in. So, as I’m actually interacting with the patient real time, I’ll utilize that AI program real time to look up information that I can easily add to my note and so that’s kind of beneficial. But it’s here.
Phillip Koo, MD [00:29:09] You’re right. It’s here. I think it’s a great tool. You know, having the human, the physician, the expertise to be able to sort of verify, check, validate some claims, I think is still vitally important. So again, you know, I could use AI to come in, ask the right questions, but just continue having that discussion with your physician because they are the ones who are managing and overseeing your care. So, we’re going to switch gears again and go into some clinical case study type discussions about, you know, how you make decisions in certain scenarios. We’re not gonna be recommending certain treatments over others but just sort of talk about what’s going through your head regarding the evidence. And you know a lot of questions have come in regarding a patient’s specific clinical scenario. And unfortunately, we can’t answer that because we aren’t practicing medicine in this forum and we aren’t the physicians of record. But we’ll try to sort of draw generic discussion points around some of these topics. So, obviously, if someone is diagnosed with high-risk localized disease, and frankly, a lot of different localized diseases, the question of radiation versus surgery comes up all the time. And I’m sure almost everyone will put it into one of the AI tools and say, oh, which one should I get? What’s sort of going through your head when you give recommendations and how do you sort of approach this? And Ben, I’ll start with you.
Benjamin Lowentritt, MD, FACS [00:30:37] The question came up earlier and patients, you know, start off often saying, hey, what would you do between these two? And I kind of set the tone at the very beginning, which is, listen, the bottom-line answer to this is both treatments are very successful, but pretty much equally successful in how well you’re going to do long-term, are you gonna survive your prostate cancer, and with that being the main question, right? Are you going to survive your prostate cancer. They’re very different journeys, whether you go surgery or radiation, and they’re different short-term and potential long-term effects. And that’s what we end up then speaking to. So, you know, the data around both of these, when you look out at studies that have been done that go 10 years, you know 15 years out, unfortunately, that’s how long it takes to really determine the effect of a treatment for localized prostate cancer, because even the bad ones generally, if it’s localized when you find it, you’re gonna live, you know, even if you eventually die of prostate cancer you’re going to live usually eight to 10 years, right? And so, in many cases. So, it takes a long time to get to the point where you can say definitively if there’s a difference. And most of those studies show, you know, minimal to no difference in overall survival. So, the opening of the discussion is, is that if there’s no true downside, one way or the other, you have two really good options. So, let’s talk about them. Right. And, and I think, you know, a big part of my, my discussion is often de-escalating some of the fears, right. Around one treatment or the others. So, we can really get to the core of it. You know, for instance, with radiation, the first things people think of when they hear radiation often, are not related to prostate cancer and frankly, not even related to radiation. They’re related to chemotherapy that might be given along with radiation and other cancers, right? So, you know, that’s an opportunity for sort of that shared discussion and education so that they understand, hey, you know, maybe we should talk to a radiation oncologist, which I recommend for everybody that’s considering either therapy. And for high-risk disease, right, you’re often talking about adding hormone therapy, but not chemotherapy to radiation. And that’s a part of the discussion as well, because the hormonal therapies have their own set of side effects. But the long-term, back to what Mike was saying about, hey, how do you balance some of these expectations over time? What is the most important function for you? Are you concerned about urinary leakage, which is a big concern for surgery? You know, these are the things that come up and are part of the discussion. And then you draw from a lot of those long-term studies if people really want to get into the data that are often kind of, some of them are more clinical trial setups, but a lot of them are actually kind of real-world evidence, registry, retrospective. A lot of them from European countries where there are big registries of their whole nationalized health system that they kind of extrapolate from. So, there’s a lot of stuff out there and a lot of it isn’t directly randomized compared to each other in a way that we can have a definitive answer, but the bottom line is they’re really good options, so you get to customize it for yourself as a patient.
Phillip Koo, MD [00:34:09] You know, I think it’s interesting and you really summarized it well. And if you go to any of the guidelines, oftentimes it lists multiple options. And I think a lot of times patients think, oh, my friend got this done and my brother or sister got, you know, or brother, whatever father got this done. But it’s never sort of this just, you know, clear, there’s a spectrum. It’s never just sort of these discrete buckets that you could fall into. You know Mike, a question comes up about focal therapy all the time. And even for this we’ve received numerous questions about focal therapy. Very hot topic, you know, there’s no level one evidence saying that cancer control is good or better with focal therapy, yet it is something that is being utilized more often. How do you approach the discussion about focal therapy, knowing sort of the limitations, but you know there might be some advantages here.
Michael Bivins, MD [00:34:59] Yeah, so it’s been a lot of new technology that’s sort of kind of entering this space. I tell people probably the number one focal therapy is active surveillance. That’s very focal. And so that’s always separating out those patients. But then you have patients that want to, so you’ll have a high-risk patient that may come in and say, you know, doc, I think I want. You know, HIFU. I’m like, well, that’s not a good option for you, right? And so, you know, understand and separate the appropriate- getting people in their appropriate risk category where focal therapy is appropriate. But for the patients that are appropriate, you know you start looking at this, you are looking at these options, whether it’s cryotherapy, whether it’s vocal cryotherapy. Whether it’s HIFU and whatnot for the audience, HIFU is high-intensity frequency ultrasound where you use an ultrasound energy to essentially kill cancer cells. Looking at radiation and now you’re looking at radiation in smaller fractions, focally to treat. Looking at, they have some new technology where they’re using electrical energy. You’re using ultrasound energy. I think it’s called TULSA. I’ve never done that myself, but trans urethral ultrasound of the prostate. I think that, you know, some of the issues in focal therapy obviously is what’s going to be the recurrence rate, and are they going to need secondary therapies? I think probably the most common ones still are going to be your cryotherapy where you’re freezing the prostate essentially, and just treating part of the gland, and then even using a high-frequency ultrasound therapy, HIFU. And so, I think those options are reasonable options for appropriate patients. And I think that’s the key is appropriate patients, those patients that are potentially low risk to intermediate favorable risk patients. Those are your patients that have PSAs less than 10. That have Gleason scores, which is your grade of your cancer, Gleason 6, maybe a few cores of Gleason 7, probably better option patients that have prostate cancer maybe on one side of the prostate. So, I think those patients are patients that are better focal therapy patients, but those patients just have to be followed very closely. But I think it is a reasonable to good option in those patients, in my opinions, that are appropriate patients.
Phillip Koo, MD [00:38:15] You know, I think you bring up some great points about active surveillance. Active surveillance is a treatment. You know it’s being watched closely and it has been shown to be, you know, the treatment of choice for three plus three and some patients with three plus four and I think we’re learning more about this. Focal therapy, it’s interesting how it continues to evolve. I think patients need to have those discussions, get the full picture, the 360-degree picture of all their different options and it’s interesting, I think Zach Klaassen is the one who told me this about like, he used the term oncologic urgency versus, you know, true urgency and when you get diagnosed with prostate cancer, you don’t really think about anything else, you just hear the word cancer. But 3 + 3, 3 + 4, actually even 4 + 3 and other degrees, there’s not the same time urgency as you might think there is. So, this idea of active surveillance or whatnot, it’s not like, it is a really, really good option and it is standard of care, that’s where we have level one evidence. So, I think it’s a fascinating discussion. I think hopefully we’ll learn more about focal therapy, about that local control as time goes on. So, Ben, we’re gonna sort of go into the advanced cancer space now. And you know, there is a drug that has been around for a while. Was first approved, we’re talking about Provenge. It was first approved with the IMPACT trial that led to the FDA approval. And then we have sort of long-term sort of follow-up and real-world data registries that have provided additional insights. So just talk to us about sort of that story and what we’ve learned with RWD.
Benjamin Lowentritt, MD, FACS [00:39:55] Yeah, and Mike please feel free to chime in because I know you’ve done a lot of this work, too, but the Provenge is an immunotherapy. It is really kind of a unique it was the first immunotherapy for a solid tumor approved in 2010, and literally it’s a way that your own white blood cells your immune cells that are taken out of your body, can be reactivated to fight cancer and prostate cancer specifically because the immune system is our most effective defense against cancer and is constantly defending us against cancer. So, any way to engage the immune is some ways it’s probably the most effective way to ever truly eradicate a cancer. And Provenge while it doesn’t usually achieve that full eradication, Provenge was one of the first treatments to show a survival benefit. It helped people live longer if they got it versus if they didn’t. The interesting thing about it is it doesn’t bring the PSA down. So that’s always created a little bit of a dynamic where some docs don’t make it available. Some patients aren’t all that thrilled with the idea of something that doesn’t bring their PSA down. But the idea that it makes people live longer to most of us is the key issue. Over time, because this was one of the first treatments in what became a flood of new treatments for advanced prostate cancer, we’ve seen it continue to be used. It’s specifically for patients that have cancer that spread that had previously been treated with hormone therapy that’s no longer working. So, what we call metastatic castrate-resistant prostate cancer. And that’s still what the indication is, and it continues 16 years later. What’s interesting is this is an example where, although the main clinical trial was done in the 2000s basically, there continues to be data that’s amassed from registries and from some of these other real-world evidence techniques, both in showing how the medicine works in combination with some of the other medicines that have come along, most notably what we call the androgen receptor pathway inhibitors that have been around, which people may know like Xtandi or Abiraterone or Erleada or Nubeqa, that family of drugs, which are often used during these, some point during advanced prostate cancer, we see that if patients, there’s a real-world evidence study that was released that shows that if patient’s get one, get just an ARPI, just the pill, versus getting the ARPI with Provenge, either before or after initiation. That they live longer if they get the combination of the two right and that is you know a really interesting thing that would have been hard to prove in a prospective trial I think there were you know questions about trials about hey do I choose not to get a therapy if I went into a trial that would otherwise help me. Well, this was looking at people that you know were not randomized into that, were looked in from the real-world experience. It was a broad number of patients that we were able to look at to kind of get to those answers. So, I think that, you know, Sipuleucel-T, which is, which is Provenge continues to be a great option for many patients along their journey, but it’s an interesting one because it’s more of like a foundational treatment for other treatments at this point, than kind of a standalone treatment in many of our practices. And that’s where the real-world evidence has kind of continued to affirm that there’s real good value in in extending survival and one of the great things about it is you know because it’s your own cells it’s not creating some of the you know negative side effects that some treatments do. You know it’s generally a very well tolerated treatment. So, you know it’s one that people can get through usually the course of a few weeks and can really add to them. So, I think it’s one that’s always been, a treatment that’s always been at a very specific point in time that it works the best. But I think what the data is showing that is for those patients that are identified and get the treatment during that window of time, they do better.
Phillip Koo, MD [00:44:24] You know, it’s interesting. Provenge, Sip-T is one of the first, I guess it sort of was vaccine and immunotherapy before it became so, so popular. In many ways, it was ahead of its time. Mike, feel free to fill us in with additional perspectives on the journey. And in my understanding, you know, there was an article published about 15 years of sort of real-world data around this topic and interesting learnings about, you now, how certain patient populations, I believe the black population responded better than the non-black population, but please tell us more.
Michael Bivins, MD [00:44:56] So a couple of things, I want to piggyback. First of all, clinical trials, and so I had a patient ask me once, how do I know if I’m in a good practice or I’m in a good medical practice or a practice that’s up to date? And I said, and I thought about that for a minute. And I said, well, if they do or they have exposure to clinical trials they’re usually state-of-the-art up-to-date clinically. So that’s always a good marker when you’re looking for, especially if you have cancer, prostate cancer, advanced cancer, even if they’re non-involved in clinical trials, do they have access to it? So that’s usually a good mark. I just want to add that to our earlier comment. You know, when you look at the IMPACT trial, I’m going to start there first, when we look at IMPACT trial, so I have a lot of Black patients and a lot African-American patients. And one of the problems as you look at clinical trials is that story, that history. And so, where Black men don’t trust the health care system. And we run into that all the time. And you see that with lack of Black men in clinical trials. And so, we’re constantly trying to get clinical trials, Black men involved in clinical trial. And it’s hard. You know, Tuskegee Institute experiment, all these things that historically have led to that sort of distrust. And then I’m always trying to figure out how to get people on clinical trials. I like first of all the marketing of clinical trials over research. Research to me sometimes just scare people away. Clinical trials is I think a better marketing tool. I think next generation therapy is even better marketing tool. When you look at the IMPACT trial, one thing that’s interesting, when you take out the time when that trial was The standard of care, you know, you look at patients that when they got metastatic, castrate-resistant metastatic disease, the average life expectancy or overall survival was around 8.3 months, right? And so, when you fast forward to the IMPACT trial, when it initially came out, you’re talking overall survival, I believe, was 24 months if you had the disease versus 21 months. To me, and this is the story I use for patients on clinical trials. That’s the one. If you got the drug, if you were in the clinical trial, whether you initially got Provenge or didn’t, you still did better than if you are not in the trial. So, you’re talking 21 months, 24 months versus 8.3 months. So, when I go out and I give this talk, I see mouths open up they just drop for a second. And that’s when I use that sort of data, that sort backstory to help me help patients understand the importance of being in clinical trials. You get standard of care therapy, you get navigators, you get coordinators, you people checking on you, you get the best imaging, you get cross over, you may probably get the drug. All these things happen that allow even the placebo to do better than what was standard at that time. So that’s one thing. When you fast forward, you proceed down into the registry and the real-world evidence. I think the PROCEED registry is what it was called. They were able to take large patient populations now. They were to look at larger populations of African-Americans, and what they found was that, and this is probably one of the few treatments where African-Americans actually had a better overall survival than anybody else, in particular any Caucasian-Americans, and so how that helps me. So, when I see a patient that falls into that category that Dr. Lowentritt talked about, that metastatic castrate-resistant prostate cancer stage and they’re African-American, I’m trying to get them on Provenge. I wanna utilize that immunotherapy effect. Now, whatever’s going on in the biology that allows African-Americans to do better on this, we’re still trying to understand. But I want to take advantage of that. I want to take advantage of that overall survival benefit. And I think they, so number one, they get better and lower PSAs. So, they got low PSA, and African-American and he has metastatic castrate-resistance. I want to take advantage of this immunotherapy effect that Provenge allows. And so, I try to get them on. Now, I may use other therapies. And we synergistically use other therapies in addition to Provenge, but I definitely want to use that. And I’m able to know that because of that real-world evidence that sort of kind of was elucidated through that real-world evidence with Provenge.
Phillip Koo, MD [00:50:10] You know, I think that’s a great story of how RWE can sort of help inform and just continue to modify practice the more we get to use it. And I imagine as all these new drugs have come to market and we start seeing real-world data and RWE studies, this will become a bigger and bigger part of how physicians sort of take all this information to make the best decisions. So, we’re just about time, just closing comments. I’ll start with you, Ben, and then Mike, I’ll turn it to you.
Benjamin Lowentritt, MD, FACS [00:50:40] No, I mean, thank you very much. And I really appreciate the opportunity to talk about this kind of concept. I think it is wonderful to have all this information at your disposal. I think where the way this will evolve is, you know, and kind of the way that I’ve always practiced it as the doctor, I’m not here to tell you what to do, but I’m here to help you make the best decision for yourself. And now that includes interpreting all these things from AI to other options and some of the non-pharmaceutical or non-clinically medical options that people are pursuing for their own care. I think all of this just adds to what we do as physicians and what that relationship should be. So that’s what you should be seeking for when you’re having these discussions. Is that confidence that you’re being heard and the ability to kind of share with the doctor what you’re thinking. Of course, it’s never always perfect, but I think that’s really the best thing that you can hope for is to get into that discussion where you feel confident that all of these things are being processed together so you can make your best choice for yourself.
Phillip Koo, MD [00:51:51] I love that, the evolving patient-physician relationships. Uh, Mike.
Michael Bivins, MD [00:51:55] Yeah, no, I will just want to piggyback on what Dr. Lowentritt was saying. I think that, you know, one size doesn’t fit all, one size fits one. I think it’s important to have that open line of communication to set goals and try to get as much information through whatever technology is available. You’re never forced to make a decision. You have time to make several visits. I also invoke getting family involved. There’s always groups, prostate cancer survivor groups, people that have gone through the journey that you can get involved with before you make any decision. And then there’s a lot of resources out there, there are national resources, local resources that can help you in your decision process. And so, you know, it’s been, I’m constantly learning the way we do things today, certainly, and both of you guys can probably echo is the way, the way that we do today is certainly different than we did them 20 years ago, even different than the way we did things two years ago. And what’s in clinical trials right now is gonna probably shape what tomorrow is going to look like. And it’ll probably look different two years from now. And so being abreast of those changes, being involved in those changes as they occur, I think only strengthens the patient. And so, and again, I thank y’all for listening to us and letting me be a part of your evening.
Phillip Koo, MD [00:53:32] Great, thank you all. A lot of questions came in, we couldn’t get to all of them. That being said, we don’t respond to them individually. We will try to aggregate them into common themes. Maybe we’ll have a separate Q&A type of webinar sometime in the future. But thank you, all, for joining on a busy evening and appreciate the time, Dr. Bivins and Dr. Lowentritt. Thank you.
Michael Bivins, MD [00:53:51] Thank you!