The Latest in Genetic Testing
Genetic Testing in Prostate Cancer: What It Means for Your Treatment — and Your Family
PCF Chief Medical Officer Dr. Phillip Koo leads a conversation with medical oncologist Dr. Elisabeth Heath (Mayo Clinic) and genetic counselor Lindsey Byrne (The Ohio State University).
- Genetic testing basics: How changes in certain genes can affect prostate cancer, and the difference between germline (inherited) testing and somatic (tumor) testing.
- Getting tested: Which patients should get each test and how samples are collected
- Your results: How they could expand treatment options, access to clinical trials, and inform your family members’ cancer risk.
- A new treatment option: The FDA recently approved capivasertib, taken with abiraterone and prednisone, for patients with metastatic hormone-sensitive prostate cancer whose tumors have low levels of a protein called PTEN, based on somatic testing.
PCF thanks AstraZeneca for their support of this program.
Transcript Below:
Phillip Koo, MD [00:00:00] So, today we’re going to be talking about genetic testing. Very, very important topic. Just to level set, we are not talking about blood or urine tests that you might get before biopsy, nor are we discussing any of those Decipher or Artera that you might get on one of your samples. We are focusing strictly on genetic testing, which we’ll dive deeper into today. But even though I say that it is very confusing. Don’t feel bad, even myself, I have to be reminded several times. So, we’re gonna dive right into it. And first off, I’m gonna have each of our panelists introduce themselves and just talk about the way genetic testing is incorporated into their practices. So, Dr. Heath, I’ll start with you.
Elisabeth Heath, MD [00:00:48] Absolutely. First of all, thank you so much for having me and, you know, having just attended PCF and watching you there and meeting all of our colleagues and friends that are really in this journey together. Again, amazing because you leave always wanting to know more answers to more questions that were raised. I think part of that is just this explosion of knowledge in molecular testing. As a general whole, we can’t even get the terminology right. Is it genetic? Is it genomic? Is it molecular testing? Is it blueprinting? Is it trying to take a peek at DNA? Is it RNA? So, any and all of that gets, I think, brought up and in different things. It is a routine conversation. In any one of our visits with patients about what are we going to do about different types of molecular testing. So, I actually do always say feels like you’re in a biology 101 class and I’m so sorry for that but in trying to explain the why, meaning why this treatment, why this strategy, why do we have to do this, it takes some time. So, it’s a complicated sort of you know issue. But kudos to PCF to try to have more of these conversations so we can bring everyone along for the ride.
Phillip Koo, MD [00:02:15] Thank you very much. I agree, I couldn’t have said it better. And thank you so much for being a supporter of ours and doing the great work that we know needs to get done. So, Lindsay, let me turn over to you, introduce yourself. I know genetic counselors are such an important role, but I know a lot of patients out there aren’t familiar with that type of role.
Lindsay Byrne, MS, GC [00:02:37] Yes, so hi, thanks for having me as well. So, what a genetic counselor is, is we’re part of the larger prostate cancer care team. So, if you haven’t had experience with one of us, they may be associated with your hospital or sometimes they can be a little bit more distant and part of the team in that way. Um, I work at Ohio state as was mentioned earlier, I’ve been here about eight years and my role when I started was to actually create a genetics clinic to see our prostate cancer patients. So, I started that, and it is a newer area. I mean, eight years feels old now, but at the time genetics was newer in that space and we’re evolving and doing and learning so much more as we go along. And so, my role is really to focus more on the hereditary aspect of genetic testing, which can be important for not only patient care, but also for the family and can overlap with the somatic testing as well, which we’ll talk about too today.
Phillip Koo, MD [00:03:48] Great, so I like that the way you describe it, sort of the hereditary aspects of genetics. So, I know you have some slides and I think it’s wonderful because as Dr. Heath had mentioned, there’s a lot of terminology, a lot of confusion. So, yes, take us through sort of the basics, Genetics 101.
Lindsay Byrne, MS, GC [00:04:08] Yes. No, this is really nice to be able to set the stage this way because of all the confusion of what this means. And what I usually tell patients when I see them in my clinic is I don’t expect you to be a genetics expert. We try to keep it very basic and as simple as possible. But setting the groundwork just for today’s discussion is just so you get a sense of when we think about cancer in general, most cancer does just happen by chance or what we call sporadic. So, you know, as we age as humans, our cells also age with us. And so over time, we’re going to develop these things in our cells called mutations. And sometimes those mutations can cause cancer. Heart disease, diabetes, and other health issues. And so, when we start looking at the population of cancer in general, a large portion of those cancers are by chance or due to aging, so to say. The area that we think about genetic testing really falls into that five to 10% or that hereditary. And so, things that we about from a prostate perspective that fall into that is, is somebody diagnosed at a younger age. And younger age is sort of a loose term, but I tend to think of it as like, so to say 55 and younger. If somebody is not in a younger age, but maybe their disease is more aggressive or higher grade. So, what we think about in that category is so to say, a Gleason score of eight or higher, or your physician has said that your prostate cancer is high, very high-risk disease, or has been metastatic. And so those are the types that tend to fit mostly in that hereditary. There are some other categories of if you have family history as well. And then when we think about doing that genetic testing. If we’ve ruled out or if genetic testing has come back negative or normal, sometimes people can fall into this category called familial here. And what that means is there’s still a clustering of prostate cancers in a family. So, let’s say you have a diagnosis of prostate cancer, but you have brother or a dad or maybe an uncle. And there’s a couple of and the family. But we can’t find a reason why the genetic testing isn’t showing a reason why, but clearly there’s still there’s still cancer in that family or prostate cancer. So, we still want to make sure that other people in the family know that there is risk there. And so just because genetic testing comes back normal, it doesn’t mean that we don’t want other men in the in the family to be aware of higher potential risk there And so when we think about that five to 10%, that’s where we really wanna start getting into the genetics. If you wanna hit next slide for me, perfect. And so, this is where some of the review from maybe high school or even middle school comes in. And so, as humans, we’re made up of billions of cells. And so, when we like zoom in deeper and deeper on the cell, so think about looking through a microscope, we wanna get down to the level of the gene. And then when we look at our gene, we wanna look at the DNA letters. And so, when we do genetic testing, you can get that done in multiple types of ways. A lot of times I tend to prefer blood. But we can also do it by saliva and sometimes there’s other exceptional ways we need to do it depending on a case by case, but when we take that blood sample what we’re doing is we’re actually then sending off the sample to look down at the DNA letters of a certain number of genes that are associated with not only prostate cancer but other types of cancer. If you want to go to the next slide. Okay. And so, when we look at one cell, we know that our DNA and our chromosomes come in pairs because we get half our genetics from mom and half from dad. But when we get down to this level, the purpose of what’s happening down at the DNA and down at gene level is if somebody is born with one of these, so to say, mutations or changes in that DNA code, that copy or that one version of it isn’t working at birth. But we still have this functional one as you can see here and if you still have that functional one that can still continue to protect the body from developing cancer and so when you have just one so to say mutation or one not working, that’s not enough to, so to say, see a cancer develop. It’s then over time that that second copy can have other mutations happen to before someone gets cancer. But what we’re looking for when we do the testing is that one starter mutation that put a person at higher risk than other people or other individuals for prostate cancer at that point. Okay, if you want to go to the next slide. And so, when we think about the two types of that we started talking about at the beginning. The area that I tend to focus on, like what we were just, so to say, talking about was more that hereditary or the germ line type. And as you can see to the right, that’s more the depiction and the picture here, because what we’re looking at is mutations present in every cell in the body. So, if one, so, to say a person or a parent ends up having one of these mutations. There’s a 50% to pass that mutation onto their children. They would share that possible mutation with siblings, so they share 50% of their genetics with those individuals. But the somatic or the tumor genetic testing is isolated to the prostate because all cancer is a mutation because it changes in the cell, right? So, a mutation is causing that cancer, but the question is, is that cancer mutation isolated to the prostate or is there a mutation that someone was born with and present in every cell in the body? So hopefully that gives a little bit more background on some of the things that we’re going to talk about in some of the terms to give a little lay of the land, so to say.
Phillip Koo, MD [00:10:24] Great, thank you very much. That’s really helpful. And I, you know, oftentimes patients, when you get a diagnosis of cancer, they’re always trying to figure out, it’s cause it runs in my family or maybe it doesn’t. And I think it’s nice to sort of be reminded that most of these are sporadic. Most of them are just sort of maybe bad luck, other factors. There is that small subset where you are inheriting things from your parents or whatnot. And I think a lot of this, we’re still learning so much more. So, the story doesn’t end here. What we’ll learn today is the story continues to evolve and the more we study this, the more you learn about it. So those numbers could change in the future. So, let’s dive in deeper into the category of germline mutations, those genes that you inherit from your parents. And Lindsay, I’ll start with you. Sort of, you talked about what is germline testing. You talked about blood versus saliva. Tell us about those differences and how should patients be approaching their discussions with their care teams about which one to get?
Lindsay Byrne, MS, GC [00:11:28] Yeah, no, great place to start. So, I did make a comment that I do tend to prefer blood, and the biggest primary reason I specifically prefer that is because new technology. So, whenever we’ve done DNA testing or germline or hereditary testing, it’s always been about looking at the DNA. But over the last couple of years, we realized that we can look at the RNA, and the RNA can tell us things about DNA. And so, what I mean by that in simple terms is thinking about this way. So, like RNA and DNA are like best friends and sometimes the RNA, can tell us secrets about DNA that DNA doesn’t want to share. And so, there’s just a little bit extra percentage that we can learn from the RNA that we couldn’t from the DNA. So, if I can get the most accurate, the highest-grade test, that’s what I want to do and that’s what I wanna attempt to do. Always that can’t be the case. Sometimes I have patients who live all over the state and getting blood work just isn’t an idea to get somewhere. So, we can do saliva. Saliva is a very, very accurate test for DNA. I think the concern is that people think that DNA or doing a buccal is not as good of a test. No, it’s a great test. You can get DNA from that way too. It’s just that we can’t at this point yet get RNA from doing the saliva testing. A lot of times, which is great, A lot of the hereditary genetic testing companies will actually do mobile phlebotomy. So, we can get blood all over the place too. If someone is having mobility issues or can’t get to a hospital, we can also get it that way. So, blood tends to be pretty easy access to get to. So that has been helpful. And that’s why I would choose it that way.
Phillip Koo, MD [00:13:16] And what recommendations do you have? Should you get genetic testing only through your primary care or your physician or your provider? Or can you just go get an over-the-counter, go online, and do it that way?
Lindsay Byrne, MS, GC [00:13:31] Great question. So, what I would strongly suggest is if you’re watching today and this feels like something you’re really interested in, you have lots more questions, talk to your provider to connect you with someone who is educated on genetics. So genetic counselors are not the only people who can order this type of testing. Obviously, your medical oncologists, your medical providers, some primary care providers are comfortable ordering this type of testing. You can order this type of testing online but usually you are associated also with a genetic counselor through certain testing companies, and some processes are involved in doing it that way, but what I would suggest is bring this up to whoever is primarily in charge of your care and say who’s the best person to guide me to. You know I watched a webinar and I saw that there are genetic counselors who may be a good place um there are places to find genetic counselors close to you if you want to self-refer. We have a national society of genetic counselors that you can find us there and put in your zip code and find a genetic counselor there or even online and do a virtual appointment that way. But again, I think there’s lots of different providers who can order this type of testing but just make sure that they understand the topic and are well-informed.
Phillip Koo, MD [00:14:48] All right, and then when should patients be requesting or discussing about getting this test? You know, if someone has localized disease and they’re getting surgery or radiation, or is it only meant for people who have disease that spread beyond the prostate? Give us some simple, you know, talking points.
Lindsay Byrne, MS, GC [00:15:05] Yeah. Now this can be appropriate for anybody with prostate cancer at all stages. I think a good thing to think about it is first off, if it’s something that you’re interested in, you want to ask smart questions. You are someone who has family history, but maybe your disease is, so to say, lower grade and maybe you’re a little bit older, so it didn’t fit some of those categories that I spoke about. Most of the time when you schedule appointments with genetic counselors, their insurance covers the appointment or there’s low to no fees, and just because you’re scheduling an appointment doesn’t mean you have to do the test. So, you can learn lots more about it on an individualized level as to if it’s appropriate for you and if you would fit that criteria. SO, I see people of all stages, all types depending on where they are and their journey of prostate cancer. Um, I do find sometimes it’s a little bit better after treatment has, so to say, settled down, meaning there’s a lot of information in the beginning about what you’re going to get, whether your surgery, radiation, hormones, chemotherapy, whatnot. And a lot of times based off of where you are genetic test results from my perspective may not be urgent. And so, it may not something you need right away, but maybe it is. So, I think you need to talk to your doctor to figure out when is the right time to get this type of result too.
Phillip Koo, MD [00:16:31] Great, and one more question before we transition over to Dr. Heath about somatic testing, but when we talk about genetic testing I know there was a lot of fear in the past about privacy about you know this being out there and then all of a sudden if you have some Mutations you might be labeled you might not be able to get insurance in the future It’s been a few years since you know, this all started where are we today with regards to privacy and protections?
Lindsay Byrne, MS, GC [00:16:57] Yes, great question. I cover that a lot, actually. So, there are laws now that actually protect individuals from being discriminated against in regard to their health insurance and their job. So, if somebody were to find some, say, an inherited genetic factor, it is against the law to discriminate from those aspects. So, from health insurance, and from your employment. So, from a health insurance perspective, we actually find that the health insurance actually utilizes the genetic test to help cover other things. For example, if you are found to test positive, we may recommend other types of cancer screening or other types or prevention, and when your insurance company knows that they will then cover those other things, so it’s actually better than probably what we think about or what we worry and are concerned about it actually is better on the side of insurance in one aspect there. The one thing to consider that it is not covered and that I do talk a lot about is life insurance and disability and long-term care. So, there are not laws that protect against that. So, a lot of times when I talk to family members who have not had a cancer diagnosis, sometimes we decide to take a pause on genetic testing to make sure all those types of pieces are in place before we do genetic testing that could unveil some type of result that could change you know cost and coverage from say like life insurance and long-term care. So those are the aspects of where we are right now, and those conversations hopefully are happening in with providers so that they can decide whether to proceed with testing or think about pausing before.
Phillip Koo, MD [00:18:47] A lot of questions are coming in, keep them coming in and we’ll try to get to as many of them as we can. If not, we’ll save them for later. But one more question, are there any tests that are germline tests that are better than the other or is it just kind of they’re all at this point just relatively similar?
Lindsay Byrne, MS, GC [00:19:05] That’s a great question. So, this area, just like lots of things on the internet can be booming with like the hottest and greatest and newest. I think there are a lot of genetic test companies and a lot of different tests that are out there that I think are good there. Here’s a few tips of things that I look for when I decide on a test. How long has a testing company been around and you know, actually doing this type of work and doing this test. So that’s really important to me. There’s a subset of genes that I’d want to make sure on there. Obviously, there are genes that can change treatment, which I’m sure Dr. Heath will talk a little bit about, but there’s usually a panel of at least 14 or so genes that I see associated prostate cancer that I want to for sure want those on there. And then what is the policy of that testing company in regard to like sharing data nationally so that we can better genetics because I think that’s really important because it helps all of us as well as what is the policy on helping like update results and connecting with the people like myself for ordering this so that I can update my patient in regard. So, there’s kind of a couple of cheat sheet things that I think about before I order a test from a company, and I think those are things to be aware of when you to talk to your provider about what company and what test should be ordered.
Phillip Koo, MD [00:20:37] Great, and I think that’s a good reason why having that discussion with your physician really helps because they will usually find those, will have relationships with those companies that are covering the right genes. You know, there was a question about how you make sure, how you approach your physicians about this. And, you know, I would say these days every oncology practice should be familiar with oncology. They should have the resources to point you in the right direction. And so. Use some of the resources we have online. We’ll talk about our testing guide that we have on our own website. And maybe you feel free to carry those into your visit and make that request for appropriate germline testing when needed. So, we’re gonna shift gears now to somatic testing. So, we’ve talked about germline, what you inherit. Dr. Heath, let’s sort of level set again. What again is somatic from your eyes and how is it performed?
Elisabeth Heath, MD [00:21:36] Yeah, and maybe before I even dive into that, some of the questions I’m seeing on the webinar here really is, okay, well, I don’t know really who’s around me, who’s gonna be able to help me, and I’m not sure which doctor I’m seeing and whatnot. One sort of available resource in the US, we may have outside of US attendees tonight, but within the US there are NCI cancer centers. That are scattered throughout the United States, they will serve as a great resource for all of us because even if you’re not sure who to reach out to and maybe your local provider in your backyard isn’t 100% helpful in directing you, asking the cancer center, which is again, NCI designated, they will be able to give you that information. Um, and Lindsay, I’m so appreciative of you and all your colleagues of what you do, uh, because there’s not enough of you. So, in addition to this is as our field is growing somatic germ line, all these fancy words, the bottom line is: We all don’t come with your testing results. So, you can order whatever but unless you know exactly sort of what’s the next step? What’s the implication? It gets really difficult and sometimes even more anxiety provoking because now you feel like I should have done something I’m not really sure really how this impacts me. So, asking those questions are critical. Now somatic testing is mostly what the cancer wants to do in your system to sort of hijack the prostate cancer world. So, it’s not baked into your original DNA, this did not, you know, come from your what I always call original programming. But it’s doing enough where it’s sort of directing your cancer to behave a certain way. So just that knowledge alone, and the germline knowledge has really changed what we do on a day-to-day basis. And that is the message for tonight, that if we’re not sure there’s impact in testing, there’s always impact. Now, it’s not in every patient, every time. And I’ll just say the difference as well. Most germline tests, at least on the global whole in 2026, just needs to be repeated once or done once. There’s confusion when you say somatic, you know, oh, you’re going to need to repeat this monthly or whatever. So, the timing is different. Where in somatic testing, because your cancer can change, you might have to have more frequent testing, whereas in germline it’s usually a one-timer. So, an interesting distinction there.
Phillip Koo, MD [00:24:12] I think that’s a great point that I’m just gonna reiterate. Germline testing, you only have to do it once. Somatic testing, it might be multiple times, but it depends. So how is somatic testing performed? Is it samples, like biopsies? Is it blood? And from your perspective as a medical oncologist, what’s the trigger by which you say, all right, we need to do again?
Elisabeth Heath, MD [00:24:38] All great questions. So, there’s really three ways to think about this. The first one is, do I have at my current situation a new area, a new, and I’ll say metastatic cancer, so. A new area that popped up during my journey that everyone is, wow, look at that new lymph node or look at the new lung metastasis, you would biopsy that and then send that for somatic testing or molecular blueprinting. So that’s one option. The second is to do it by blood. So much like germline, we can also do the fancy testing on blood. We call those liquid biopsies. Which kind of makes sense. You’re not putting a needle in anyone; you’re drawing a tube of blood. And what you’re hoping to capture there is as the cancer cells move from wherever location to a new location, none of them or not all of them will make it to the full cycle as it goes around your body. So as those cancer cells die, they do give off their DNA to the bloodstream so that we can pick it up and then blueprint that. Now, just a caveat. Not every prostate cancer cell wants to give up their DNA. So notoriously, prostate cancer sometimes hangs on like, well, I’m gonna die as a cell, I’m going to take my DNA with me, and you can’t have it. So sometimes people get sort of, you know, led down a path of like, well, I did my liquid biopsy, and it didn’t show anything. So again, it’s all about interpretation. What does that mean? And then lastly, one possible way as well, I couldn’t get anything out of the blood. There’s really no new area or it’s not safe for a biopsy. And my doctor’s kind of worried that I might cause more damage. You can always go back to the original prostate biopsy or prostate surgery. And we call that still tissue, but it’s archival tissue. Now, the old worry was, well, that was, I don’t know, that was seven years ago. Is that’s going to be good enough? And the answer is yes, actually. As long as there’s enough tumor, you can get enough nuclear material to be able to do the sequencing or the profiling. So, you can gain information there as well. So, there’s lots of ways to tackle this.
Phillip Koo, MD [00:26:54] I think that’s another great point, you know, when you get a biopsy or you have your prostate removed surgically, that tissue is usually still archived and sitting there and being able to go back and sample that is a really great method. So, talk to us about… You know, kudos to you. You testified in front of the FDA to help get approval of one of these new drugs, which we’ll talk about a little later, that’s driven by some of these genetic mutations. The methodology becomes confusing. I think we hear terms like IHC or NGS, and even for physicians, there’s a lot of confusion. In the patient community, this probably gets overwhelming. So… How do we empower patients to make sure they’re getting the right tests to answer the questions so that it can be actionable?
Elisabeth Heath, MD [00:27:50] Yeah, I think programs like this, really, the one takeaway is whether you understand the biology, whether you remember what the DNA and all those slides and conversations should or would look like, it’s really just ask one question to your team. Do I need genetic testing? That’s it. And you can take that as a launch point where then your doctor and your team should say, well, yes, and in this scenario. Some may then refer to a counselor. They may be in a health system where it’s automatically drawn and only the positive tests go to the counselor because of just resource. Some may say that we’re going to talk about this, but you’re so overwhelmed that we’re going to about this at another time because we have to focus on what’s the treatment plan. Some may say, well, you’ve had that testing five years ago, but now we need to move on because your cancer’s not behaving. We need to see somatically what’s going on with your actual cancer behavior. So many of that is more DNA and RNA, and frankly, it’s all confusing, but the reality is NGS stands for next generation sequencing. So, audience here may not recognize that, you know. There is a lot of genes that we have. So, what we know is what we know, but from even 20 years ago to what we do today is astronomically different. We have over 22,000 genes in our blueprint. And so, any one of those could get wrong messaging, wrong signaling, you might be okay one day, not okay another. It’s astonishing that the humans, all of us, are doing as well as we can, because there’s a lot of communication that can go kind of wonky, but… What’s really critical is asking that question, do I need genetic testing? Not even a statement of I had genetic testing, because let me tell you, there’s others that say, well, 23andMe, I had a genetic testing. I had XYZ testing. So just go in there and see what your team would like to do. Now, the tried-and-true way of how we look at things, This IHC stands for immunohistochemistry. All that is, is your pathologist who has whatever tissue biopsy will do a set of stains and look for stuff. And guess what? All of oncology still does that routinely. If you go to any health system and you ask a pathologist, that is happening with multiple stains with multiple cancers all day every day. Why? Because that still works. And for those attending outside of the US, that’s still the gold standard for many, many cancers, including prostate cancer. So, it doesn’t have to mean that fancy testing is expensive, and you have to get a science degree to understand what it is. Tried and true regular testing that happens every day in every corner of the world is still really valuable to know about.
Phillip Koo, MD [00:30:51] Great, you know, there’s a comment in the Q&A and I think it’s worth sort of reinforcing. Very true, we go back to the prostate specimen that was taken out of surgery. That is more germline testing doesn’t really reflect where your disease and some of the metastases might look like so that’s a good point
Elisabeth Heath, MD [00:31:11] Can I just clarify though? It’s not germline testing, right? So, when you look at that tissue, it is still somatic. Yes. So just to clarify, but it is prognostic of that moment. So, for example, you may not know because that original sample was never tested. So back to your who gets tested, you know, for germline, at least by our guidelines known as NCCN. If you have local disease, you can get germline testing if you are unfavorable, intermediate, high risk, very high risk and metastatic. And your insurance should not push back in those instances. Where I’ve seen people get some pushback is, well, you have low grade prostate cancer. What did you do that for? But you then work with the genetic counselor and say, well you know, I did that because guess what? I’m 45 with this and I’m a young onset prostate patient. And I have a sister with breast cancer and a mother with breast cancer and a cousin with ovarian cancer, you may meet other indications because of your family history. So, there’s a lot to this that isn’t just one size fits all, but it tells you at that moment, how is it gonna behave? So, if you already have, let’s say, the breast cancer two gene or BRCA2, it’s gonna behave a little nastier than sort of one without. So just a little glimpses to the behavior for the future.
Phillip Koo, MD [00:32:39] So that’s a great transition. So, you get the genetic testing, you get this report, which is almost like this alphabet soup and can be very, very overwhelming. So, let’s sort of start, Lindsay, back with you in the germline. What are the things that you’re looking for? I think a lot of times people, they might get it for germline, they might be expecting a BRCA gene, they might not have a BRCA alteration. Is that good news or bad news? How should they sort of interpret what they’re seeing in those reports?
Lindsay Byrne, MS, GC [00:33:08] Yes, so when we get a germline report back, there’s typically three results we can get. It can be negative, which means that we have looked at a portion of genes that again, a person is born with, and these genes are normally functioning in the body. And so, we’re evaluating them to see if there’s any mutations. And so, a negative report means that we did not mind any underlying mutations that are causing issues. And that at this point, we don’t have a reason for the prostate cancer. So then at that point, I would also say to the patient that because testing is negative, I wouldn’t put them at a higher risk of other types of cancer that may have been associated with a positive result. We do still look at the family history to say maybe there was other family members with family history of cancer, and so they need to be aware of that. But the other important thing is, is because their test is negative, they cannot pass on that result to their kids. Meaning, because they don’t have a genetic mutation that they were born with, they can’t pass that on to their kids, so their kids are not at a higher risk of hereditary cancer. The second type of result is if it’s positive. So, if we do find a positive result, that does mean that we found some type of germline positive result. Meaning there was a mutation. Depending on what that mutation is, then at that point, it depends on what I say next. If it’s something like a BRCA1 or BRCA2, those are two of the most common genes that we see in the prostate population. If it something like that, that could indicate some treatment changes potentially. The other piece about that is it indicates possible other cancer risk that we need to talk about. Because with those two genes, we not only can see prostate cancer, but men can have breast cancer risk. They can have melanoma risk. We can see their siblings, meaning this is important for them to share with sisters and daughters, not just men in the family. So, we don’t just focus on prostate cancer. We need to think of the family as a whole because their children then now have a 50% chance to have that same genetic mutation, which can put at risk for other types of cancer. And so that is the biggest piece to think about in regard to, again, the difference between germline and somatic is thinking about other things outside the prostate and how this also can impact the family as well. And then the third type of result that we can get is what we call an unknown result or a variant of uncertain significance. And what that means and the way I describe that result is I call it an in-between result. So, an actual genetic finding was found. So, there was some kind of change in the DNA, but there’s not enough data to say that that particular change is causing cancer, or is it just a change that makes you different from me? So, we all have genetic changes. Sometimes those genetic changes don’t cause disease or don’t cause issues. They’re just changes that make us unique. And so, what’s happening with that in between result is that there’s just not enough data from the lab that we use, from the lab nationally, that we know to say hey we’re worried about this result and it’s going to impact you know your care and such. So, a lot of times with that result most of the time when I see that category results over time the lab will end up reclassifying it into a negative or positive and usually about 90 percent of the time it gets reclassified to that negative, and so most of the time I will treat it towards that direction and we’ll talk about that with the patient and their family. And that was why one of my top three things to think about when I use a lab is does the lab that you’re using update you when they decide to reclassify that result? Some labs do and some don’t. And to me as a provider, it’s very important that I get updated because I want to tell the patient, hey, there’s been enough data now that this result is now negative, or we’re actually worried about it and we’re going to call it positive, and now we want to start testing your family members and change your care for other cancers at this point too.
Phillip Koo, MD [00:37:16] So is that occurring automatically in the background?
Lindsay Byrne, MS, GC [00:37:20] Yes, if the lab says that they’re doing that. And so again, that’s why the labs that I like to use are doing that because what they’re doing is anytime somebody comes, a sample comes in a lab that has the same result as you, they repoll everybody that’s had that classification and say, is there enough data to say this is a negative normal change? Or is there enough data now to call this pathogenic or positive and disease causing? And they also gather and the other one of the other important things that I said is does the lab that we’re using share their data outside the lab to better other labs and better us as you know providers to change that classification as well. Some labs don’t like to share data, and some do and it’s not a like share your data with your name and date of birth. It’s share your data as like this test result was negative, this test results was positive, so that they can help all of us understand actual genetic results and such. To me, that’s a good thing.
Phillip Koo, MD [00:38:21] Great. So, you know, I like the way you put it, negative, positive, or sort of unknown, and each of those scenarios could be very overwhelming and anxiety provoking. So, make sure you communicate with your support network and your physicians and your care team about this. And if you are confused, you know, ask the questions you need to get answered. So, Dr. Heath, we’re gonna shift back to the somatic testing piece. You get that report. I’ve seen some of them and my eyes just glaze over. So, what are you looking for? How can you use that to help make sure the patients are getting the right treatments?
Elisabeth Heath, MD [00:38:57] Yeah. Well, I think this is that impact that a lot of the questions here on the webinar is really asking, you know. Yes, it’s important to do germline. It may affect the next generation or the generation after that. So, this is something where we can have additional knowledge about your own, you know, family and your own family members that we never had before. So that in itself is impactful. But when you have, let’s say, metastatic disease and you’re thinking, Okay, it’s another test. I’m now overwhelmed. What’s the point? And the point is that it might alter what treatment you get or what treatment options are available. And that is something that is quite new to this field. Now, the pivotal group who’s already had this is actually lung cancer. You know, lung cancer not too long ago was just lung cancer, you either had non-small cell or small cell, and you got chemo, just different types. Nowadays, lung cancer is basically the most diverse molecularly characterized cancers out there. So, you might have an out fusion. You might have, you know, other fusions that then change what you get for treatment. Prase cancer, we’re just at the beginning of that. So, the results come very similar to the way Lindsay has described hers. So, we have the positives is known as pathogenic variant or likely pathogenic variant. So, it’s not technically a positive or a negative, but it’s just a category in terms of whether something is so worrisome that you look at it and say, oh, I can do something about that or keep my eye on that to see if it changes. We also have the variant of unknown significance. I call that the gray category where. I don’t know what this means. I don’t know what it means because maybe we don’t have enough information. And as that builds, that might also change and we might get the upgrade or the downgrade just like in germline testing. And then you have, don’t see anything, just benign, everything functions as it should. So, we have similar ways to take a look at that. But nowadays, many of the testing report, and again different vendors have different ways to report things. Some will say, oh, you test positive and let’s pick on a very common one, the BRCA2 gene. And when you test positively for that, you might be a candidate for a PARP inhibitor, which is a class of drugs that are available now that are FDA approved. And it will say that typically on the actual report. And in addition, it will also, many of the vendors will have, Hey, you might qualify for this clinical trial. Um, and you might want to investigate that as something if you’re interested in, and we always encourage people to think about clinical trials because we made these advancements because we did clinical trials, um, that it opens up that treatment menu. So, the big change though, the really, really big change happened end of last year when if you are newly diagnosed with metastatic disease with prostate cancer, you, if you test positive for the BRCA2 gene, you will also have a different recommendation from people who do not. And that recommendation difference would be you get an injection, which is the, you know, get rid of your testosterone, you get a hormone pill, which we know is ARPIs or androgen receptor pathway inhibitors, and then you get the PARP inhibitor. So, all of that all of a sudden has changed and that became FDA approved in December of 2025. So, talk about right hot off the presses, not even a year that’s been there. And that’s an opportunity where life can be extended. So of course we want people to have that, but you only know if you’re a candidate if you test. And if you don’t test, you don’t know.
Phillip Koo, MD [00:42:56] That’s great. So, you know, it’s amazing. This is sort of precision medicine at its best. My monitor went out, so I couldn’t hear everything. But you talked about the PARPs. I think you, did you mention the PTEN as well?
Elisabeth Heath, MD [00:43:08] No, so that’s the other drug, so.
Phillip Koo, MD [00:43:10] All right.
Elisabeth Heath, MD [00:43:09] So literally, just, you know, May of this year, what happened, well, when you find out that the brakes to sort of keep a lot of the other parts of the prostate cancer is kaput, and it was sort of never there, you now have a new drug known as Capivasertib. The trade name for that is Trueqap. That’s also in combination with a, you, know, a strategy to get rid of your hormones and another androgen receptor pathway inhibitor. I mean, that literally is not even six months old in terms of information, but if your team doesn’t check, and in this case it’s that immunohistochemistry again that you were saying, yes, you can check with the fancy somatic testing and you may capture 50 percent of you know the scenarios where you would have this missing break known as PTEN, but you don’t even need that. Not that I’m advocating you don’t do it, but you also need to do this immunohistochemistry test on the tissue to see if you have this deficiency. So, the goofy part is we’re so used to having things be too much of. This test is you don’t have any. So again, to confuse matters, we want to see people who don’t have greater than 90% of them. Not have the stain. So, it’s the absence of the stain that makes you a candidate. So, it is tricky, but your doctor should know this because FDA approved drugs already are clear in terms of what is that companion test that needs to happen.
Phillip Koo, MD [00:44:44] You know, it is very confusing. You’re right, absence of or presence of. But I think in general, the patients should recognize it’s such a different day and age today where it’s precision medicine. You’re targeting something specifically. Whether we’re talking about radioligand therapies, PARP inhibitors, now capivasertib, it’s a such a cool new advancement and that’s why it’s so important. We really are grateful to you for testifying and helping to advocate for these new drugs that really help certain patients a great deal. So, there are a couple questions submitted asking about Decipher, NDX tests, Artera. Again, those are different types of tests. They’re not germline or somatic testing, so they are covered in different resources that we have on our website as well. So, we’re running sort of towards the end of this. I do want to make sure I give a chance for both of you to sort of cover topics or anything that you wanted to reiterate or talk about again. Lindsay, I’ll start with you.
Lindsay Byrne, MS, GC [00:45:43] Yeah, I would say, um, I liked what Dr. Heath said to just ask a basic question, you know, is genetic testing appropriate for me and to help that get you to the right people, to have a larger conversation and whether that equals hereditary and somatic testing. I think the other thing that I want to like mention is the two tests can be very similar. But their technology is different. And at this point, it’s very challenging to just get one test. So, one test doesn’t cover both areas at this point. The goal is that that will eventually hopefully happen. And you can kind of make that happen by getting different sample ties. But at this point, the technology is different between the germline testing and what is happening in the somatic. So, they’re looking for different things. The somatic is thinking about what can I do to treat your prostate cancer? And the hereditary testing is looking at why did this happen? Were you born with this? Is this why this happened? What does this mean for other types of cancer risk for you? And what does this mean for your family? So those would be the things I’d wanna make sure that you took away from today is the difference between the two and the importance of how they are different, but they can both be very impactful if they’re appropriate for both of you.
Phillip Koo, MD [00:47:04] Great, Dr. Heath, before I give you the closing words, I do wanna, you know, the question has come up a few times. If you’re doing well, if you’re, let’s say you’re castration resistant, your PSA is low, you have no meds, you’re doing’ well, is there a role for somatic testing? Or should you wait till things progress?
Elisabeth Heath, MD [00:47:24] Yeah, I mean, typically I think it’s more helpful in your clinical sort of what are we doing next is upon progression to do that. You know, there’s now a big push that when you’re newly diagnosed, the metastatic that you already checked to see what is happening now, just as a baseline test, but that’s not necessary. So, I think that, you know, just to know sometimes, you just have to be careful in terms of what does that afford you? There are also the other take-home message other than please ask if genetic testing is appropriate. Even just launching that conversation is going to be helpful for everyone here on the webinar. But it’s also recognizing the expectations. So, you know, you take something as common as BRCA2. When you do somatic testing, it’s up to 20 percent. So, it’s not 80. It’s not 90 percent. So, when people are like, oh, I don’t have that, most don’t. So, we are looking from beyond that. So again, from a clinical trial standpoint, we recognize there are multiple other clinical trials that have just specific gene mutations that sometimes don’t care whether you have prostate cancer or not. So that’s really another way, especially for those men on tonight who have had other treatments that have been more of the standard of care and you’re looking for options. The way other options can open up for your treatment would be, okay we don’t care that it’s prostate cancer, oh I tested for this gene that we’re not sure, but there’s a study that’s looking at the genetic mutation and the drug is then possibly open for me. So, our goal is to present as many available options as possible. This is a tool to get you some more options and we really hope that a conversation on germline and somatic testing can help you in your journey.
Phillip Koo, MD [00:49:18] That’s a wonderful summary. I think hopefully all the patients and caregivers and loved ones on the webinar today recognize that it’s important. Oftentimes it gets overlooked. And this is where that knowledge and that power to go into that room, ask the right questions, have that discussion when appropriate, and get the testing done if appropriate is really, really important. And hopefully people here recognize there’s so much more to come. And that’s what’s so exciting about this whole space is. I think as a field, we all, need to get used to this idea of genetic testing, whether it’s germline and somatic. And I think we’re gonna continue to learn more. And I love what you’d said about clinical trials. When you get it, it will often let you know if you are eligible for a trial. And if it is, it gives you more treatment options. So, thank you so much. This is a really challenging topic. And I know everyone on the webinar is walking away more educated and more empowered. So, thank and everyone enjoy your evenings.