Applying Genetic Therapy

Applying Genetic Therapy

 
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Genetic testing can indicate disease behavior, therapy success, and pre-disposal to prostate cancer. Therapies and decisions can be guided based on genetic profiles and knowledge of specific mutations. Discover genetic tests, genetically targeted therapies, and how to apply all this new, complex information to your prostate cancer.

Dr. Scholz:  [00:04] Welcome to PROSTATE PROS. I’m Dr. Mark Scholz and this is my cohost, Liz Graves.

Liz:  [00:11] This episode we’ll be talking about genetics and prostate cancer.  There’s been an explosion of new technology and there are tons of new genetic companies popping up.  How much of this is actually useful for prostate cancer patients?

Dr. Scholz:  [00:24] Yeah, it’s amazing how many new companies have started up recently and we’re seeing a lot of the detail people coming through our office and touting these new tests, a simple blood test, perhaps a mouth swab, and you find out every gene known to man.   What do we do with all this new information?  Reflecting on this podcast, I thought that it would be sensible to work backwards from the tests that are specifically relevant to treatments or actions that would change as a result.  It is possible to do testing and find a myriad of genes, but so many of them don’t have clinical relevance.

Liz:  [01:05] Okay, so we have clinical relevance we need to address.  There are two categories of application: there’s genetic testing for the newly diagnosed and genetic testing for advanced prostate cancer patients.

Dr. Scholz:   [01:18] Yeah, so let’s address the newly diagnosed first.  These tests have been around for over five years.  There are three companies that are offering tests: Prolaris, Oncotype, and Decipher.  These companies will evaluate the prostate biopsy, the information that was used to give you a Gleason Score originally and take that information and let you know if the cancer is likely to behave aggressively or not.  This is scored out usually as a percentage likelihood that the cancer will progress or spread outside the prostate or even lead to death in the next 10 years.  That’s useful information.  The tricky part is that many times this information is validating what we already know from the Gleason Score, the PSA, and other scan results.  The people who seem to be most benefited by this type of information are the men with favorable Gleason 7s.  We call this Intermediate-Risk, with our color scheme we call it a Favorable-TEAL.  They’re the people that are sort of at the tipping point: maybe they can watch it, maybe they have to treat it.  One of these three tests can be helpful to point to whether or not the disease is likely to be aggressive in the future in that specific individual.

Liz:  [02:44] So they can really help people be confident in the decisions they’re making, whether they’re thinking about being an active surveillance patient or deciding on treatment.

Dr. Scholz:  [02:52] Exactly, this historically was very important because when active surveillance first came on the horizon about 10 years ago, it was such a unique and unexpected idea to just simply monitor people.  So to have genetic testing that would validate the safety of that approach was extremely valuable.  Now of course, more and more it’s becoming mainstream to do active surveillance in Grade 6 patients.  I am not using the tests as aggressively in Grade 6 patients because we now have a greater level of comfort doing active surveillance in these patients.  Do we really need another test to tell us what we kind of already know?  It’s certainly okay to do the testing and nervous patients will still want to do the test to confirm that it is safe to do active surveillance.  But, as I mentioned previously, it’s really the favorable Grade 7s where people can go either way that we really appreciate having this type of information.

Liz:  [03:57] So you have a lot of new patients coming into the clinic and it sounds like you’re kind of picking and choosing who you’re giving genetic tests to.  Is this your choice?  Are patients asking for genetic tests?

Dr. Scholz: [04:09] Yeah, when patients want to do the test, we’re certainly more than happy to perform it.  It’s generally covered by their insurance.  It’s not a difficult process at all because the biopsy information is archived, so there’s no need for an additional biopsy or anything invasive.  The problem is that there is no test out there, genetic or otherwise, that is 100% accurate.  So when you start doing testing on people where you kind of already know what you want to do, you can really create some confusion if you perform a test that contradicts what you think is the truth.  Now you have to make a decision: is the genetic test telling you something you didn’t know, or is the genetic test result actually wrong?  In a small percentage of cases that genetic test will point the wrong direction.  It won’t be indicating exactly precise information.  So testing is much more useful when you’re sitting on the fence wondering which way to go then it is when you kind of already know what you need to do. Sometimes you’ll actually create some confusion by doing testing when you already know what you want to do and then you get a test that points the opposite direction.

Liz:  [05:22] There’s a different type of genetic test that I’ve heard about called know error® for newly diagnosed men.

Dr. Scholz:  [05:30] Yeah, it’s spelled k-n-o-w error, kind of a tricky little play on words.  This is the fascinating technology which helps patients “purchase insurance” against the possibility that the biopsy slides, the material that was removed when you had your needle biopsy, put on a slide and then sent off to a pathology department doesn’t get switched with some other patient’s slides.  You say “that could never happen, Dr. Scholz.  How could they do such a dreadful thing?” It happens.  There’ve been large studies showing that the risk of this happening at various labs, even very good ones, is perhaps in the range of about 1% that the slides and the information that you received on your pathology report came from a different patient.  They don’t even represent what happened to you and the other patient got your numbers.  So the know error® company came up with the idea of comparing the genetics on the slide with the genetics obtained through a mouth swab on your body and comparing those genetics to be 100% sure that the genetics are the same and that the information on the slide and on your report is actually your information.

Liz:  [06:50] Are you doing this test a lot?

Dr. Scholz: [06:52] Generally with a 1% risk, we’ll look at a case and if it makes sense, if the pathology is kind of what we expect, we have other information from the MRI, from the PSA, from the history, the test, which I believe runs about $500 is something that we’re not in any way doing routinely.  But if questions arise or something doesn’t quite seem to fit or we certainly have clients that are really nervous about these things and want that level of assurance, we will do it.  This gives you 100% certainty that the biopsy that was performed and the information derived from it is actually coming from you.

Liz:  [07:37] So these tests can be helpful for a very specific group of newly diagnosed men.  That’s mainly the Gleason 7s.  It’s also important to remember that there is the know error® test that can help you ensure that your results are yours.  So let’s jump into the next category we’re talking about, which is genetics for the men with advanced prostate cancer.

Dr. Scholz: [08:01] Yeah, so we address genetics and advanced prostate cancer because as you’re probably all aware, anyone can get genetics and we’ll talk about that a little bit later.  You don’t even have to have cancer to look at your genetic heritage and all kinds of things.  But we talk about it because in this podcast we’re trying to limit it to the real practical outworking of what this new technology provides.  The issue is connecting a genetic abnormality detected by a blood test or a mouth swab, or even a biopsy, sometimes they’ll do needle biopsies too, and connecting that with a treatment. The treatments that have been discovered for genetic deficiencies, think of the BRCA genetic deficiency or ATM, using oral medications, kind of like chemotherapy, say Olaparib or Rucaparib.  These medicines are not without side effects.  So if someday we develop a medicine that fixes a genetic problem that doesn’t have any side effects, that the medicine doesn’t have side effects, then it will be expanded probably to all stages of prostate cancer.  But, because right now the types of medicines that are available for people with genetic deficiencies all have potentially significant side effects, it’s really only people that have more serious disease that can justify taking them.  That’s why genetics is typically reserved for more advanced prostate cancer.

Liz: [09:34] So what these tests do for men with advanced prostate cancer is they can help determine the success of the therapy.

Dr. Scholz: [09:43] Exactly. The medicines that are being designed now to fix specific genetic deficiencies are very targeted and they don’t work as well unless that genetic deficiency is present.  So it makes a heck of a lot of sense to test for it to see when it’s present and then to embark upon a treatment, I mentioned Olaparib or Rucaparib, with a much higher expectation of success.

Liz:  [10:11] One gene that everyone’s pretty familiar with is BRCA which is very common in breast cancer.  Men with prostate cancer can have this gene.  If they find out they have this gene, they can use a specific treatment that will work better for them.

Dr. Scholz: [10:27] Exactly, kind of a cousin to that is called ATM.  So BRCA and ATM deficiencies are a signal that these medicines that I mentioned before, Rucaparib and Olaparib (Lynparza is a trade name of Olaparib), will be effective.  How often does this genetic deficiency occur in advanced disease?  It appears in about 10% of men.  So it’s not overwhelmingly common, but when it’s present, these medicines can work extremely well.

Liz:  [10:59] So you mentioned Olaparib which is FDA approved for ovarian cancer.  Are there genes for other cancers that treatment exists that you can use for prostate cancer?

Dr. Scholz:  [11:11] Yes, exactly, and someday in the future we may not define the cancers as prostate cancer, ovarian, or lung.  We might start to define the cancers based on the genetic abnormality that’s discovered with biopsies or a blood testing.  The reason is that it opens the doorway to knowing what the right treatment is.  It turns out that for other cancers, say for bladder cancer or lung cancer, they have discovered specific genetic deficiencies that can also be targeted with specific medical therapies.  So, one other reason to consider doing genetic testing in prostate cancer is to look for another gene abnormality that might be common in say lung cancer or bladder cancer and then use a lung cancer or a bladder cancer treatment to treat the prostate cancer that has that same gene.  This is again not something that happens terribly commonly, but it does offer a window of opportunity for an unexpected medicine, a medicine used normally for another type of cancer to be useful in a prostate cancer patient who happens to have the same genetic problem. 

Liz: [12:24] What else are we looking for?

Dr. Scholz:  [12:25] Well, there is an interesting genetic issue called microsatellite instability.  This is picked up by genetic testing.  It’s pretty uncommon, maybe only one to two percent of patients with advanced prostate cancer.  But it turns out that an immune medicine called KEYTRUDA becomes almost a magic bullet in these patients.  A high percentage of people with microsatellite instability will go into rather dramatic remissions with this immune medicine called KEYTRUDA.  So that’s almost like winning the lottery when this is discovered.  As yet, I haven’t come across the case, but I do know of colleagues that have and they remark on the tremendous responses that are seen with this medicine.  The medicine is well tolerated, people can take it for extended periods of time.  It’s an infusion every three weeks.  So it is really like a godsend when this particular genetic abnormality is detected

Liz:  [13:22] Another genetic test called ImuDx for immunotherapy.  We talked about this on the Intelligence of Immunotherapy episode.  If you haven’t listened to it yet, you should go check it out.

Joyce Turner, MS CGC: [13:33] Genetic counseling can help you by helping you to make choices about whether or not genetic testing is the appropriate course of action for you.  One of the benefits of genetic testing is to empower the individual and gain enough information to make decisions regarding their medical management.  If you are considering genetic counseling and testing and want to determine if it’s right for you, you should talk to a health professional.

Liz:  [14:09] So we’ve been talking about genetic testing.  What actually are we testing?

Dr. Scholz: [14:14] So genetic testing can be done from the lining of your mouth, your doctor may ask you to do a mouth swab.  They can do it from blood, just a simple blood test.  We’ve also in the past on occasion taken lymph nodes that have cancer in them by surgically removing them, or spots on bones, asking a special radiologist to do targeted biopsies, needle biopsies of those spots to get tissue.  That’s getting less and less popular because the blood tests have improved so much that it’s really not adding much to go in and start removing things surgically.  Obviously that sounds uncomfortable.  It is.

Liz:  [14:55] So we take the sample and we send it to the company.  How long should patients be expecting results in?

Dr. Scholz: [15:02] Well, it certainly depends on the company, but typically within a week, I’d say, sometimes you’ll get it within 48 hours.

Liz:  [15:09] So if they find a genetic abnormality in your patients, does that mean their whole family should get tested?

Dr. Scholz: [15:16] So that’s a good question because there’s actually two types of genetic testing.  One is to test the genetics of the tumor itself, and that may not be the same as the actual patient’s normal cells.  Then the other genetic testing of course is when we test the normal cells to see if there’s some preexisting genetic abnormality.  So, sometimes we pick up that people have a preexisting genetic abnormality and that’s what led to their cancer.  When something like that is discovered, say the BRCA gene, it is sensible to tell them that maybe their children should get tested because that may have some implications for their risk, their children’s risk of developing cancer down the line.

Liz:  [15:59] Okay, Dr. Scholz, so you’re saying that some people may have preexisting genetic abnormalities.  Does this mean we all need to run out and go get genetic tested?

Dr. Scholz: [16:08] In my mind that’s the big question these days.  We have all these wonderful tests that are available at our fingertips, the 23andMe and other ways that you can look into your genetic history.  Fascinating stuff.  Many patients have asked me that question.  I haven’t formulated a uniform answer yet.  I think sometimes of course, discovering that there’s a specific gene that could lead to a future cancer, it’s useful to know about that so you can be vigilant.  On the other hand, you can find other genes that look scary and we don’t have the slightest idea what to do about them.  So we can kind of scare yourself, but you can’t do anything about it.  So it cuts both ways.  I haven’t really decided, even for myself, if I’m going to have just routine genetic testing.  I even have a predisposing possibility through my own heritage: my father had a very rare type of cancer being a man, yet he had breast cancer.  This suggests that he has a higher risk of having the BRCA mutation.  So someday I’ll probably get around to testing myself to see if I inherited that.  Of course, I don’t know for sure that he had it, but he may.  I hesitate because once that information is out, you can never put it back in the box.  Everyone needs to think carefully before they jump into genetic testing because they may get information that they wish they didn’t actually know.

Liz: [17:40] Thank you for the perspective, Dr. Scholz.  If you’re curious about learning more, there are professionals, called genetic counselors, that you can talk to about your questions regarding this, who will be able to give you good answers.  If this topic is interesting to you, make sure you watch the mid-year PCRI conference.  It’s available for access at pcri.org.  As always, email us questions to podcast@prostateoncology.com and help us out by rating, reviewing, and subscribing on Apple Podcasts.

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