Ralf Schwiede joins Dr. Alicia Morgans to share his experience with metastatic prostate cancer and discuss the importance of germline and somatic genetic testing. They explore how these tests can identify inherited cancer risks, help guide treatment decisions, and provide valuable information for patients and their families. Ralf also shares how understanding his test results has helped him navigate his diagnosis with greater confidence.
Dr. Alicia Morgans:
Hi, I'm very excited to be here today with Ralf Schwiede, who is joining me to talk about germline and somatic genetic testing. Thank you so much for being here with me, Ralf.
Ralf Schwiede:
Thanks for having me.
Dr. Alicia Morgans:
Wonderful. So I wanted to talk to you about that particular issue, how we think about testing for certain targetable mutations in metastatic prostate cancer, but I'd love if you could just set the stage and tell everyone about your cancer diagnosis and where things are right now.
Ralf Schwiede:
So I've been diagnosed with metastatic prostate cancer last year in July, was actually one day after I did my passion triathlon where I actually PB'd in this, just a side fact.
Dr. Alicia Morgans:
Great.
Ralf Schwiede:
And then after that, I had germline and genetic testing, and I am on ADT and I'm on darolutamide on treatment. I've got zero testosterone left in my body, but I'm still happy that I can keep on going. I can keep on doing what I love doing.
Dr. Alicia Morgans:
Wonderful. Well, thank you. And thank you also for sharing that you had germline and tumor-based somatic genetic testing. So we can talk about this because it's really important, whenever someone has a diagnosis of metastatic prostate cancer, it's actually recommended on the US guidelines at least. And I know you're visiting us from British Columbia, but I think in Canada too, recommended that we try to get both germline testing and somatic or tissue-based testing, tumor-based testing.
And the reason that this is so important is that we can find about half of the mutations that we want to target in each of these types of testing. And also importantly, it's possible that there will be overlap in these tests where one test could find some of the things that the other test could find, but it's also possible that if you don't do both, you could miss some of the alterations.
Let's start with germline testing. This is the testing that we do to try to understand if you inherited something from your family that ultimately you could have in your system, and then would be shared with brothers and sisters and potentially cousins or children in your family. Now, you had a family history of prostate cancer as well as breast cancer, I think, which made it especially important even in addition to the metastatic prostate cancer diagnosis, right?
Ralf Schwiede:
Yes, correct. My father had prostate cancer. My mother actually just a few years ago had breast cancer. And for that reason, it was important for me to get the testing done, and then to see for my daughters to see is there any variant that may be important for them to know to then take the next steps that we have.
Dr. Alicia Morgans:
That is so important. I think I see a lot of patients in clinic who say, "Well, I don't have sons, so is it really important for me?" And I tell them this can actually change the way that daughters are screened for cancers a little bit more intensely than it does for sons. Because daughters may have different screening for breast cancer. They may have MRIs instead of mammograms, for example. They may start much younger in their screening process. And certainly the ovarian cancer doesn't have a standardized screening, but having the gynecologist know that the individual young woman has this risk can be so important. So I'm glad that you recognize that and we're interested in looking at that for your daughters. Did you find anything in the test that was something that could have predisposed you to cancer? Or what did the results look like?
Ralf Schwiede:
The results weren't 100% clear. There were variants of uncertain significance. And we said at some point, and I believe that would be the point when my daughters are at the age that we would recommend that they get certain testing done as well. And for myself, if I would've known the combination earlier with my father, then I guess I would've had PSA testing done earlier myself. And I'm 59 years old now, and I had my first PSA test done 2023. And I think knowing what I know now and how everything interacts, I would've been a bit more aggressive on how things are treated. Because I was actually treated for two years on prostatitis. Something totally different, but knowing how it interacts, everything. And I think it's important that we got that done.
Dr. Alicia Morgans:
Yes. Well, family history to your point is so important. And for those people who know their family history, keeping in mind that there was a diagnosis of prostate cancer and thinking about screening, or talking to their urologist about 10 years earlier than their family member's diagnosis can be helpful. But it's also helpful when you're seeing a urologist, as you said, and you're being followed to try to talk about that family history.
So I'm glad that you did get your PSA checked, and I'm really glad that you ultimately got to treatment at a point. And I'm also glad that you did the testing. VUSs or variants of uncertain significance can be really confusing. And it sounds like you talked to your doctor about this, right?
Ralf Schwiede:
Yes, we did talk about it, but they said when we spoke about the variance of uncertain significance, he said it's not really much they can say or not really much they can do about that. It's unfortunate it didn't help clarify my confusion that I had. But on the other side, he said I shouldn't see it as something bad because it doesn't always mean that it's in the bad directions, could be in a good direction as well. So that's why I didn't really worry too much for myself about that anymore.
Dr. Alicia Morgans:
And you shouldn't. So usually when we know that a mutation in a certain gene is associated with causing cancer, we call it a pathogenic mutation. And that's what people will see when they get reports back that have a mutation that is associated with causing cancer. And a VUS in most cases, 95% plus of cases, if not even higher, are actually benign.
They're just abnormalities or even just a uniqueness about ourselves and about our gene that isn't causing cancer, but is something that we find when we do this type of testing. Importantly, the companies that run these tests, these germline genetic tests, keep a database. And if they find that something is changed from a VUS to a pathogenic mutation, in most cases they will reach out and contact the doctor who sent the test, and also in a lot of cases, contact the person who had the testing to make sure that they know of this change.
That happens actually quite rarely, but it is possible. So keeping that testing information on hand and checking in with your doctor every few years just to say, has anything changed here is something that people could do if they feel anxious, or just want to learn more.
Ralf Schwiede:
It's very good to know. Yeah.
Dr. Alicia Morgans:
Very good. All right. Well, let's switch gears a little bit and talk about somatic or tumor testing. So this is really helping us understand the genes in the tumor, in the cancer itself, which are definitely going to be different in a lot of ways from the rest of your body, which is what the other test is testing. You had this test as well. Did you have a test that was a blood test? Did you have a test that was sent on a prostate biopsy or something else?
Ralf Schwiede:
So the test that I had was based on the samples that were taken in my targeted biopsy that I had. And to be honest, those results there were... First the doctor said, again, I have some variants of uncertain significance, especially with a p10. And otherwise I said, oh, I want to see... Me being an engineer, I wanted to see it myself and see what does it mean?
But to be honest, when I looked at tier one, tier two, tier three, what does this all mean? Tier 3A, tier 3B, and I spoke with him about it in basically showing that the TP53 is not that active is something that may be expected, what he said. But again, the variance with the p10, the variance of uncertain significance, not really... Again, there he said it's not something that should be seen as something bad. And what is positive is that the RB1, there was nothing seen on that.
So again, gave me a bit of relief to say nothing to worry too much about. And especially my response that I had after then with ADT, it went well. I had radiation, but with ADT, and then especially when I started darolutamide, the deep response with my PSA dropping so far, and then in combination, knowing that there's nothing of significance in those genetic testing, that gives me some relief.
Dr. Alicia Morgans:
Yes. Well, and it should. I think this type of testing, this tumor-based or tumor genetic-based information, somatic testing we also call it, is sometimes very confusing. The reports can be done by many different companies, or sometimes they're done by a laboratory within someone's healthcare system.
Many academic programs have their own testing system within their own hospital, and so they're not necessarily going to look the same from one report to another. Some reports break down the importance of the mutations, and the certainty of the mutation as being something that's going to be targetable with treatment in these tiers. Tier 2, tier 2, tier 3. And really the ones that are causing or driving the cancer's growth are typically going to be in tier 1 or maybe in tier 2. And other alterations might be listed lower down with less certainty and maybe less commonly found as being abnormal in this tumor.
But many reports just list the genes, say whether there's a mutation and whether it's actionable, or causing the cancer or not, and don't get into all of those details. So all of these differences are potentially confusing, and it's important to talk to your doctor about it just like you did. Things like p10, p53, these are common mutations that don't necessarily have a therapeutic target, or aren't necessarily things that we can use medicines to attack.
Although there is a new medicine that targets p10 for some people. And so it's important, again, just to ask these questions. And that's probably why they said some of these you can just recognize that it's very common in prostate cancer, but doesn't change our treatments. And that's probably what many people who have these tests will hear. But some people will have things that come up on this test, the somatic or tumor test, or the germline genetic test that is something called an HRR mutation. Things like BRCA1, BRCA2, ATM, these different mutations that we now have drugs to target.
And so doing the tests, both types will help us understand that. And the reports, even if confusing, can be sorted through with your doctor. And if there's a treatment that can be used, that doctor should be able to talk to you about it.
Ralf Schwiede:
I think adding what you are saying, it's very for... Because we as patients, especially the family as well, worries about every stage that we're going through. And then having the certainty of saying, okay, there isn't anything of real significance and going forward with the treatment that I have, I think it's very, very important that I was able to do those tests and that those tests are done. I think that is very, very important. Yeah.
Dr. Alicia Morgans:
Yeah. I could not echo that loudly enough. Having the tests done regardless of the results is the most important thing. And then acting on the results or just recognizing that the results say there's no change in treatment here based on these results, or implications for my family, that's the next most important thing.
Ralf Schwiede:
Because part of the journey is as well to, in simple terms, to keep mentally sane. Because if you worry, worry, worry, I do try to have and spread a positive attitude. I have hard days, but in general, having certainty of some things, they help me getting through this.
Dr. Alicia Morgans:
Absolutely. I think that's absolutely true. And doing these tests can give you the certainty. One piece to just add, as the cancer changes over time, after people are on treatment for a long time, sometimes we send the tumor type of genetic testing again in the future. If we biopsy a new spot or sometimes we send it from a blood test to understand if after all of that treatment that someone's had, the tumor has changed in a way that now it is holding a mutation that is driving its growth that we can target with either clinical trials or with medicines that are approved.
So sometimes the tumor type of genetic testing, that's something that we would want to repeat in the future. So keeping that in mind for patients I think is also important that this may be something that needs to be done again in the future.
Ralf Schwiede:
Oh, that's good to know.
Dr. Alicia Morgans:
Yeah. Wonderful. Well, I thank you so much for your time, and sharing your experience.
Ralf Schwiede:
Thank you.
Dr. Alicia Morgans:
Wonderful expertise today, Ralf. Thank you.
Ralf Schwiede:
Thank you.
This interview was produced with the generous support of AstraZeneca Pharmaceuticals