Genetic Testing for Bladder Cancer, with Petros Grivas, MD, PhD, and Marianne Dubard-Gault, MD, MS

March 23, 2023
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In this podcast, Cancer.Net Specialty Editor Dr. Petros Grivas talks to Dr. Marianne Dubard-Gault about what people with bladder cancer should know about genetics and genetic testing, including what information genetic testing can provide, how it can inform bladder cancer treatment, and what to expect when meeting with a genetic counselor.



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In this podcast, Cancer.Net Specialty Editor Dr. Petros Grivas talks to Dr. Marianne Dubard-Gault about what people with bladder cancer should know about genetics and genetic testing, including what information genetic testing can provide, how it can inform bladder cancer treatment, and what to expect when meeting with a genetic counselor.

Dr. Grivas is a medical oncologist at Seattle Cancer Care Alliance, clinical director of the Genitourinary Cancers Program, and professor at the University of Washington School of Medicine. He is also an associate member of the Clinical Research Division at Fred Hutchinson Cancer Research Center. Dr. Dubard-Gault is the medical director of the Cancer Genetics Program at Fred Hutchinson Cancer Research Center and an assistant professor at the University of Washington School of Medicine.

View disclosures for Dr. Grivas and Dr. Dubard-Gault at Cancer.Net.

Dr. Grivas: Hello, I'm Dr. Petros Grivas. I'm a medical oncologist and serving as the clinical director of the Genitourinary Cancers Program and professor at the University of Washington Fred Hutchinson Cancer Center. I'm very excited and thrilled today to discuss with one of the amazing leaders in the field of cancer genetics, Dr. Marianne Dubard-Gault, who is my colleague here at UW Fred Hutchinson and has been such a wonderful human being and advocate for her patients and also really a key opinion leader in the field of genetics and the implementation in patient care. Dr. Dubard-Gault, welcome, and I will let you introduce yourself.

Dr. Dubard-Gault: Thank you very much, Dr. Grivas, and it's a pleasure to be here. So thank you for the invitation. I am Dr. Marianne Dubard-Gault. I am a trained oncology doctor and a trained genetics doctor, and my focus now, as Dr. Grivas mentioned, is in the cancer genetics world where I help people either get genetic testing in the first place and/or their family members have interventions for their screening and early detection. I'm also an assistant professor at Fred Hutchinson Cancer Center in Seattle, Washington, and then at the University of Washington on the other side. And I lead the Cancer Genetic Survey Center at Fred Hutchinson Cancer Center. And I have no disclosures.

Dr. Grivas: Thank you so much, Marianne, and again, thank you for helping our patients. And I'm really, really excited today because it's a very important topic, not frequently discussed. And I really, really wanted to make this happen, and thanks to Cancer.Net for helping us getting the word out there. I have no relevant disclosures in this topic. My disclosures are listed on the ASCO website. And Marianne, I will start us off by asking you, just for the audience to set the stage, can you define what we call “genetics”? What exactly are we referring to?

Dr. Dubard-Gault: Yes, that's actually very important. That's probably the first thing that happens in the clinic when we talk to patients is, what is genetics anyway, right? So genetics is the study of the DNA or the genetic makeup that we all have. And that makes a person who they are, right? So looking into the genetic makeup to make sense of it and inform treatment or other interventions.

Dr. Grivas: Thank you much, Marianne. And I think it's so important again for our patients to understand the definitions here. So let me ask you, can you define the difference between a genetic mutation versus genetic alteration? How would you explain that to a patient?

Dr. Dubard-Gault: I think about them in a similar way. So, to me, a genetic mutation or alteration is a spot in your DNA. So there's a long stretch of letters, and there's a spot in there that either was copied or wasn't copied properly over. And so that leads to a command that kind of not being executed properly. And so an example of that would be if I gave you the 2 words “red” and “bed,” those 2 words would mean totally different things in your mind. And so if you were supposed to hear “red” and you heard “bed,” then downstream will be a different outcome.

Dr. Grivas: Thank you so much, Marianne. And this is very important because for the audience as you pointed out nicely, the genetic code, the DNA translates a message, alright, that becomes a protein and eventually a function of the cell. So if that code, if that message is misspelled, it can lead to different altered and changed-up protein for the cell. That has implications and can potentially predispose someone to cancer. So if we can also help the audience understanding the differences between what we call “somatic genetic mutations” and “germline mutations.”

Dr. Dubard-Gault: Absolutely. And this is also something that comes up every time because they're part of the same groups of things overall, right? So somatic means tissue or tumor. And germline, or hereditary, sometimes you'll hear that word interchangeably means inherited or hereditary or part of the genetic makeup or the code that you were born with. So different parts of our body have different genetic mutations. And that is why even with 2 identical twins, they won't have the same moles on their skin, or they won't have the same medical conditions, even if they have exactly the same genetic code. And it's exactly the same for a person who has a tumor, right? The DNA or the genetic makeup they were born with will stay exactly the same as they grow older, but the genetic makeup their tumor has as the tumor grows can change and make more or have more mutations. So testing different parts of the body will help tease out which ones of the mutations are located where? Is it in a tumor only? Is it in the genetic makeup you were born with or is it part of that transition between the 2?

Dr. Grivas: Thank you, Marianne. I think this is great when we explain to the patients what exactly mutations, alterations, means, and the difference between a somatic tumor testing, as you said, mostly to help define treatment options. And what you very nicely discussed are germline testing, looking at hereditary predisposition to cancer that can impact the patient and also family members and the broader family. And one kind of take-home message may be for our audiences, when someone is about to see an oncologist or their provider, is greatly helpful if they can do quote-unquote "their homework" and try to understand and delineate and capture as much as possible regarding the family history. And sometimes it's hard, especially when you go to distant relatives, cousins, nephew, nieces, it's more difficult, but it can help a lot and inform that discussion and whether a referral to a genetic counselor or geneticist is relevant. So that's what we try to do with nurse navigation these days to help inform people with cancer before their appointment how they can maximize to capture that information, it can be helpful to them and for the provider. And the next question, Marianne, is how common are these genetic germline mutations in people with bladder cancer?

Dr. Dubard-Gault: I think the answer is still out there. We don't have the complete answer today. We don't know all the genes that are implicated in bladder cancer today. So given that, we probably don't have the full or complete answer as to how many people with bladder cancer would have it. But kind of to get close to the answer, as close as we can possibly be today, I think it depends on the group of patients with bladder cancer that you test, but I would probably give a 1 in 10 people with bladder cancer would have an inherited genetic mutation.

Dr. Grivas: And that's very helpful Marianne. And of course, varies, of course, across the different scenarios and the family history as you mentioned, the age of cancer diagnosis. And sometimes it's interesting in patients with urothelial carcinoma, cancer in the upper urinary tract, like renal pelvis, kidney problems, or ureter, there seems to be some higher frequency of germline mutations in that as opposed to bladder cancer. Of course, it can happen in that scenario, but seems to be some higher frequency in the upper tract cases, is that right?

Dr. Dubard-Gault: I agree. Not all cancers are created equal, right? In the bladder, that's probably also true. So depending on where it starts, the type of cells that are involved, and how the person was born with certain genetic predispositions, it may very well affect how all of these are linked together in one line of event versus maybe something that happened randomly or occurred that we don't have a one specific answer or a combination of answers.

Dr. Grivas: That's a great point. And obviously, there are the huge impacts that we discussed to help prevent cancers in the bladder family. Cancer prevention mode, I call it, when I explain to the patients before they see you. And also, some patients are also asking, in addition to that family benefit in my brother’s family, is there any potential impact on the treatment selection for the bladder cancer? Any comment?

Dr. Dubard-Gault: Yes, I do believe there is actually more today than ever before, especially with the new medications that have come around, right? So sometimes a genetic mutation will happen in the DNA or the code that is important for repairing the code of the DNA, or sometimes it will happen in an area that helps boost the immune system or the response to the cancer cells by the immune system. So in that case, if we find a genetic mutation, then we can use a chemotherapy that concentrates or targets that area that's not working well and fix it, right? So that's one really important area. And then another area, and Dr. Grivas, I know you've done a lot more clinical trials and studies that involve the DNA that makes new blood vessels for feeding the tumor. And in that case, you can use a chemotherapy that would block the body from making those new blood vessels and basically shut off the feeding system to the tumors. And so that way, the genetic testing can also help the patient find a therapy that would work better for them.

Dr. Grivas: That's a great discussion. And we're doing many clinical trials to test this hypothesis. This assumption kind of practice, and we try to look at particular therapies that might be relevant in the context of a germline mutation. And those clinical trials are very promising. And I always encourage our patients to consider subsequent trials. And the other aspect of it, as you said very nicely, is that a patient who may have some changes in the code encoding some enzymes, some proteins that repair the DNA, this can cause some more mutations. And in this particular scenario, there may be a much higher response to immunotherapy. That immunotherapy may help shrink those tumors with what we call more unstable genomes. So that's very interesting to see that across tumor types, to your point. The other question is if someone is referred to genetic counseling, how can they be better prepared for their appointment?

Dr. Dubard-Gault: I think the most important thing that I would say is to really embrace it and go. Because it's often something that makes people worried that they have a genetic predisposition in the family, and they may not necessarily be ready to hear it or want to have as much information, especially being diagnosed with a cancer at the time. And so really embrace it and go for the genetic visit because it is something that could be very useful and bring information not only to you as a person for your own treatment, and/or then for your siblings or relatives for them to have access to interventions they would not have otherwise.

Dr. Grivas: What question do you think people should ask their providers? How can they better prepare for the visit with the provider overall regarding the topic we are discussing today?

Dr. Dubard-Gault: That's also very important because as much information as you can gather is really important. So, if possible, gathering as much information about your family history as you can, as Dr. Grivas mentioned. And sometimes you can't have all the information, some grandparents died, they did not share the information about their cancer diagnosis because they didn't want to upset the family. Sometimes you have no information on one side of the family because you don't know who your father's parents are, for example, or a certain relative may be OK now and they have cancer later on, and you will probably not have that information, right? We can still do the genetic test knowing that some of this information is missing. So keeping in mind that as much information as you can get is good. And if we have a lot, that's helpful, and if we don't, we will kind of factor that in our conversation. And a few other tips I would keep in mind is the timing of the testing matters. Sometimes doing the testing earlier in the process is a good thing because it takes a little while for the results to come back.

That's a sophisticated test that takes usually 3 to 4 weeks. There are many different types of genetic testing; that's also very important. You may very well have more than 1 genetic test, as Dr. Grivas mentioned. The test on the tumor, the test on your genetic makeup from a blood sample or a saliva sample. I mean, keeping in mind-- I think the third one that's really important is keeping in mind that when we do the genetic test, the results may implicate other people in the family straight away. And I'll share an example of this because this comes up in my clinic very often. So I met a brother not so long ago who had bladder cancer. No exposures, no smoking, nothing to point to a risk of bladder cancer for him, but his sister had uterine cancer earlier on before the age of 40, and then had colon cancer as a second primary cancer. And the test came back with the genetic predisposition we talked about, Lynch syndrome. And this diagnosis basically explained his cancer diagnosis on why he had an unstable genome in his tumor. And his sisters, both of his sister's cancer. So by proxy by testing him, we tested not only him, but his sister as well, even if we'll do the sisters confirmation tests, we know the sister is likely positive for this.

Dr. Grivas: Thank you so much, Marianne. The very useful information. Again, the positive impact and benefit for the broader family. What happens during and after the initial meeting with the genetic counselor or the geneticist?

Dr. Dubard-Gault: Well, I love genetic counselors, I think they're very helpful. And I work with them on a day-to-day basis. So, what they'll do is they'll sit down with you either in person or telemedicine or telehealth from the comfort of your own home or on the phone. I don't like the phone as much as I like the interpersonal connection with a person. But they'll help you draw out your family tree, put all the people in the family on the page together to kind of see and share a pattern. They'll talk a little bit more about the different types of genetic testing one person could have. And then they'll facilitate getting the genetic test that is best for you and your family. And so that really is the most important piece because they'll work with your oncology doctors and other doctors to come up with the best option.

And the one that matches the family story. And then if you're in person, you could even provide a sample, either a blood sample or a saliva sample, right there. And then the authorization and all goes through, and then the results usually will come back a few weeks later. And then the genetic counselor or myself as a genetics doctor will sit down with you when the results come back to review what they mean, not only what the actual test says, but what they mean specifically for your treatment, and/or for yourself or your screening and interventions later on, and/or your family members, if they need to be tested themselves or what needs to happen for them. And then you can obviously be referred to a specialist like Dr. Grivas or others for a colonoscopy or for thyroid ultrasound or some other tests that may be needed for these screening interventions in the future.

Dr. Grivas: Great points. And as you mentioned before, it's important for the patients who see the provider to discuss their family history-- close and distant family history as much as they can, and they can even ask whether they need to see genetic counselors. Sometimes the patients can remind a busy provider how important that is and ask for a referral, it’s definitely important to ask the provider.  Very quickly, Marianne, you mentioned before the value of testing for both the patient and the broader family in terms of what we call cascade testing and cancer prevention. You mentioned the example in your patient, can you very briefly comment on that and what is the value here again for the patient and the family?

Dr. Dubard-Gault: Absolutely. And sometimes someone with a genetic predisposition, so someone born with a genetic predisposition to cancer, can be at risk of more than 1 cancer in their lifetime. So sometimes, when they're diagnosed with the cancer, we find this genetic predisposition to said cancer, but it may come with other cancers as well, just like the bladder cancer and uterine cancer and colon cancer. And this may not be something a person would want to hear when they're diagnosed with cancer, but it is good information that will stay there for the future as they go through the treatment for having interventions done, right? So it's good information to talk about with their doctors so their doctors can order the colonoscopy or different screening protocol. We'll recognize a certain intervention like removing the uterus of someone in the family so they would reduce their risk of uterine cancer. And obviously, genetic mutations tend to be shared in the family. It's most likely something was inherited in the family rather than new in a person. So each person who's positive for a genetic predisposition, we think about their siblings, their children, their nieces and nephews, and those people may have exactly the same genetic predisposition or mutation, and they may be at risk of the same kinds of cancers. And that's the reason why they would get this information to be eligible for other screenings as well. And interventions.

Dr. Grivas: Very important, and very useful for the patient. Before we wrap up, Marianne, can you comment a little bit on barriers to testing, out-of-pocket costs, culture, trust, literacy, busy practice, competing priorities?

Dr. Dubard-Gault: Yes, absolutely. I think the main ones are awareness that bladder cancer can be a genetic cancer. It's really rare, but it can be. And so keeping that in mind, because then if you're not even referred or that doesn't come to mind, it may not get us to doing this genetic testing. The diagnosis of cancer is a lot to take in, right? So it may not be the right time to do it right away, but keeping that in mind for the future is also important. The cost. Sometimes the generic testing isn't covered by Medicare, unless there are specific criteria that we talked about, a family history of specific type or early diagnosis and all these things. And the genetic counselor will really help push to find as much information as possible to get the test covered. And there are lower-cost options out there. And I think the last 2 are really the privacy of the results. People worry that this information will be shared outside of health care, and/or sharing themselves this information with their family members when they're probably or maybe not ready to disclose their cancer diagnosis. So I find that that's maybe less or lower on the list, but in order to keep in mind as well.

Dr. Grivas: Thank you, Marianne. Maybe the last 2 very quick questions for you. Germline testing and options and value of counseling. I know you have touched upon that already. But did you have any departing thoughts on that part on the value on the patient and the family and any other considerations, for example, DNA biobank, etc.?

Dr. Dubard-Gault: Absolutely. So, I find that meeting with the genetic counselor, even after you've had genetic testing and the results are back, is a valuable thing to do. And not necessarily right away, but later on down the road, right? So because this field, the genetics field, advances rapidly, it's possible someone will be testing again or there are more genes or more mutations out there we weren't testing for a few years ago that we would test again. So keeping in mind, we can test again. And that meeting with the genetic counselor is always useful even if you have heard a little bit about it already. And then the DNA biobanking piece, if that's a service that's available to you, keeping your DNA for the future, when the technology is not advanced yet, is very important because we know for sure the knowledge will change and will bring new treatments and new options for screening and interventions, so keeping the DNA for the future is very useful.

Dr. Grivas: That's a great point. And because technology is evolving very fast, the methodologies are changing, many times we have the information and genetics team, and counselors and geneticists try to keep track and follow those people who are tested to see if any of the information may potentially make a mutation that was of a certain significance-- something that may be significant down the road as more information are coming in. And because of this rapidly evolving nature of information, it is good for people with cancer and also any affected family members to stay in touch periodically and follow up with the genetics team. Maybe the last question for you, Marianne, is if you have any take-home message for our people, our audience today so they can remember going forward.

Dr. Dubard-Gault: Information is power. It really is. And having this information helps your doctors bring the best treatment to the tumor that you have and not somebody else's, right? And for the family, that may bring an answer that was longed for really generations before you, and that would help not only have this information, but take it forward and say, "You know what? I'm going to do something about it because we can." So to me, that's the reason I transitioned careers, and that's the message that I want to keep sharing.

Dr. Grivas: What a great message by Dr. Dubard-Gault. And now we're trying hard to involve and engage genetic counselors and geneticists to our multidisciplinary clinics. And bladder cancer is a great model for multidisciplinary approach, and we try to engage them earlier. So we need more of you, Dr. Dubard-Gault. We need more geneticists and genetic counselors. And with your background in oncology, it's fantastic to work with you. Thanks again for a great discussion. Thanks again to Cancer.Net for all they do for the mission of patient education and of course ASCO. And thanks to the audience for your attention today. Thank you.

Dr. Dubard-Gault: Thank you for inviting me.

ASCO: Thank you, Dr. Grivas and Dr. Dubard-Gault. Learn more about genetic testing and cancer at

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