Video: Genetic Testing for Advanced Prostate Cancer (Royal Stage) | Prostate Cancer Staging Guide

Prostate Cancer Staging Guide | Transcription

Hi, I'm Dr. Scholz. Let's talk about prostate cancer. 

In this video, we're going to cover genetic testing for advanced prostate cancer. Selecting treatment for men with advanced prostate cancer is an art form and it starts with the standard fare: Hormone treatments, chemo treatments, but it's possible that over time that those different types of therapy will run out of gas and won't function, won't keep the disease in check. New ideas might come through genetic testing of the tumor tissue. 

Certain mutations that occur in other types of cancers—kidney cancer, lung cancer, colon cancer—can also occur in prostate cancer and if those mutations are detected the treatments that are used for those types of cancer can be used for prostate cancer. The problem with prostate cancer genetic testing is that the tumor is located, generally speaking, in the bone. Biopsy of the bone can be uncomfortable, and it doesn't always give the type of tumor tissue that's needed for analysis. Fortunately, there's some newer testing procedures of the blood. Turns out that prostate cancer and many cancers release tumor-related DNA into the blood and that can be analyzed for the possibility of different mutations. Tests like this are called Guardant 360 and FoundationOne and there are other tests available. 

So what specifically are we looking for when we do testing for mutations in prostate cancer? There are many many mutations, but for most of them, we don't have a treatment connected with them that would lead us to appropriate therapy. But there are specifically two types of mutations that should be looked for due to the availability of good therapy. The first group is BRCA, CHEK2, and ATM mutations. There's a medicine called Olaparib that's FDA approved for the treatment of ovarian cancer that can be effective in prostate cancer patients with this type of mutation. These mutations occur in about 10% of men with advanced disease, so it's worth checking for it. The Olaparib, while it's effective, does have side effects and it's not generally used for earlier stages of advanced disease, but if other options are running out it's a very logical consideration. It's a pill; [it] has side effects somewhat similar to mild chemotherapy, but is tolerable and can be effective. 

Another mutation that is incredibly important when it occurs—it's uncommon, only occurring in about 1-2% of men with prostate cancer—is called "Microsatellite Instability," and this is a very interesting mutation because if it's present almost all patients will respond to an immune therapy called Keytruda. Keytruda has been shown to have responses in prostate cancer of about 10-20% of prostate cancer patients in general with advanced disease, but when microsatellite instability is detected on genetic testing essentially 100% of people respond and responses tend to be dramatically good. So sadly this is a fairly rare mutation, but it's a fairly simple thing to test for this with these new liquid biopsy type blood tests, and if this type of mutation is detected it can totally change the outcome for someone even who has run out of options and has very advanced prostate cancer. 

Lastly, when talking about genetic testing for prostate cancer, there's another blood test out testing for a specific molecule in the blood called AR-V7. Very popular medicines for advanced prostate cancer are Xtandi, Erleada, [and] Zytiga, and these medicines are very effective at taking men with hormone-resistant disease and putting them back in remission. However, when the AR-V7 molecule starts to appear in the blood, these pills tend to stop working, and this test is useful for helping to detect if there's going to be a problem with these medicines in the near future. So AR-V7 blood testing is another potentially useful genetic test for men with advanced prostate cancer. 

So in summary, the genetic testing of prostate cancer, as of yet, is not offering huge inroads into improved effectiveness of prostate cancer treatment. There are certain little niches where it can make a big difference, and it is appropriate now that we have access to these better blood tests to do this type of testing. As time goes on and as understanding deepens, there's going to be many more therapies as a result of genetic testing and we eagerly await that day.