Genetic Testing in Prostate Cancer

Transcript:Raoul S. Concepcion, MD, FACS: There are a couple big issues here that I think that our audience really needs to understand. There is testing to determine the potential treatment of the patient who has been diagnosed—usually the ones with the higher grade, more aggressive, by definition, histopathologic diagnosis of the prostate cancer. We can try to determine how that testing might affect their future therapies, or, as you said, Mike, testing in order to give better family counseling—who’s at risk down the road?

The question is, when should you start testing? Should you start it at diagnosis? Is it for everybody with prostate cancer, regardless of if they’re low, intermediate, or high risk? Or, should we be testing at the time when they start to progress to CRPC? Neal, what are your thoughts on that?

Neal D. Shore, MD, FACS: It’s a very good question. It’s a very complicated answer. It’s not simple at all. One of the things that clearly is now very high on my radar is that I have a young man, or, it even could be an older man—and young/old is very subjective, right? The older I get, the younger chronologic age becomes. But, having said that, there is demonstrable evidence of mortality from prostate cancer, these other important hereditary solid tumors such as breast, ovarian, gastrointestinal, pancreas, and there’s an uncle, father, or brothers where I’m now telling my patients to go and get genetic testing for their children, their nieces, and nephews.

There are many companies that are out there that will do this genetic testing. It’s easy to do. You get it from saliva or you can get it from blood. And most of them are offering some forms of 1-800 call-in numbers and information. For the genetic counselors who are out there, it takes time. As Evan said, this is the challenge. It takes expertise, and it takes time. And the challenge is, in the United States today, my understanding is there are only about 3000 counselors, nationally. And so, at many of our best academic institutions, there’s a several-month waiting list to get in, even in these places of higher learning and more sophistication. In most of the rest of the community, you might have to drive hours to find someone. So, I’m not giving you a very quick and direct answer because I’m working through this.

One of the things that I’m really hopeful for is that these companies—and there’s several of them out there, as well as the companies that have new therapies—could use this genetic testing as a compendium diagnostic so that we could better personalize our treatment decisions. It could help us work together for educational purposes. We really have to lift the threshold of what we’re doing. It’s very, very low right now.

Michael A. Carducci, MD, FACP: Yes, I think education is a key part of it. Whether we can have videos, or you have to meet with a genetic counselor, I think a lot of that’s coming forward. But there’s a step forward, and not only do you have direct patient marketing for these assays on television, but your doctor has particular tests. Some are paid for by insurance, others are out-of-pocket. There are those issues that you want to bring up. And then, there’s a whole other list that aren’t just these things about hereditary, but are more of panels of genes that tell you that you’re going to recur or you’re not going to recur. “You’re going to have metastasis.” They tell you these sort of things. The patients need to know what test they are getting and what it means. “I have a risk.” “My family has a risk.” There are other tests that the urologists use more frequently to predict whether a patient should go on active surveillance or whether they should get combination radiation therapy or other types of approaches.

Raoul S. Concepcion, MD, FACS: I think it’s pretty clear. You all of have stated that we have to move beyond this notion that we take a good history and, I think, it’s, unfortunately, a lost art. We need to do a better job of going to the next level. Again, asking about all these other tumors that we know. Historically, as you said Neal, we’ve been relatively naïve about not considering them into the whole play of how this affects prostate cancer—the breast cancer patients, the ovarian cancer patients, the pancreatics, gastrointestinal tumors, Lynch syndromes, and those types of things. I think we need to do a better job, and I think it can be done. But within this day and age of electronic health records, it could probably be done, really simply, through a kiosk or online.

I think what you were saying, Mike, also bears, again, the reiteration that what we’re seeing, now, is commercially available tests that people can call up and get for $99. Those are different types of tests. Some of the panels that Neal, you were alluding to, are of companies that are out there specifically looking at a panel of genes that are specifically looking at some very distinct gene mutations. Once again, I think about the whole complexity of once all that comes back. I know Michigan has recently started up a dedicated prostate genetic counseling center. Are you guys thinking about doing that, Evan, in Washington?

Evan Y. Yu, MD: We started the first one. Colin Pritchard and the New England Journal of Medicine paper showed that 12% of patients with metastatic prostate cancer have germline alterations. This was from our center. And Heather Cheng is a wonderful young faculty member in our center who is focused on genetics. She is working closely with Mary-Claire King as well. She started a high-risk genetics clinic.

I think the dilemma for our center is a little bit easier because one could argue, if you asked a trained geneticist when you should screen somebody, they would tell you that if the incidence is over 10%, you should take a look. And in looking at it—11.8%, almost 12%—one could argue that maybe we should be testing everyone with metastatic prostate cancer.

Now, again, we note the fact that we don’t have enough genetic counselors. I don’t have the training, but Dr Heather Cheng, who runs our high-risk genetic clinic, also has a genetic counselor in that clinic. So, when I see patients who have metastatic prostate cancer, especially those who have an interesting family history or an interesting personal history, I send them to Dr. Cheng’s clinic and she does the counseling. With a genetic counselor there, they decide if it’s proper to do testing or not. She’s doing research studies, too, and family studies as well.

One of the things we haven’t talked about yet is, what if you find something that we know about like BRCA2 or ATM? What if you find something that we don’t know about yet? These variants of unknown significance, or uncertain significance, may pan out to be something in the future.

So, we find all these genetic alterations. We don’t know what to do with them. That’s when you really need a genetic counselor, or somebody to do the adequate follow-up with that as time goes on. It’s not a trivial issue that we can just all run off and do this in our own in our clinic and test everyone. We really have to do it right.

Michael A. Carducci, MD, FACP: It happens at Johns Hopkins. We have a tumor board for the physicians to go to. Someone has got this testing, or we’ve ordered the testing, and you need someone to help you interpret that so that you can sort through some of these variants and decide whether they have meaning—where this predicts for gastric cancer. What do you tell them about? We don’t take people’s stomachs out just because they have a risk for it. How do we follow that person? There’s information that I need in order to go back and educate my patients. There are counselors. There are people who really know genetics, who can look through these panels and say, “Not worrisome.” Or, “Yes, worrisome.”

Evan Y. Yu, MD: Or, “Maybe worrisome.”

Michael A. Carducci, MD, FACP: To figure out what you should really be communicating to the patient.

Neal D. Shore, MD, FACS: But one other thing about this, Raoul, that’s important and we’re leaving out what part of this conference was about, is there’s no perfect algorithm for it. But the thing that we haven’t even mentioned, as well, is patient choice. There are many patients who don’t want to have this information. And then, what do you do if you obtain this information? What do you do if the patient doesn’t want the information or doesn’t choose to share the information with his or her spouse and/or children? There are some very interesting and challenging ethical issues. People leave. People move. You’re holding on to this information.

We’re really at the beginning of this beginning. That was really the wonderful thing about this conference and in trying to get some level of consensus from a lot of folks who are perceived as key opinion leaders in various fields. It was really great to see that. So, the manuscript has been submitted. Hopefully, that’ll come out in the near term and folks watching today could read through some of these questions that were asked. Frankly, there was not a tremendous amount of consensus amongst a lot of experts getting back to the challenge of where we are.

Evan Y. Yu, MD: I think that that is exactly the biggest challenge we face. Naturally, if you present it to a patient as, “I can get this panel test. If I find an abnormality in this gene—and maybe you have a 12%, or maybe even up to a 25% if you add in the somatic alteration, risk of having one of these DNA repair deficiency gene abnormalities—this could help your treatment down the road.” This may predict response to a PARP inhibitor, to platinum chemotherapy, etc. Is a patient going to say, “Well, no, I don’t want to do this test,”? You have to take the time to tell them that there could be implications for their family. Maybe you want to know, maybe you don’t want to know. There could be implications downstream for insurance. Who knows what’s going to happen with preexisting conditions, right?

I’m starting to have patients refuse to do the testing. But if you just say, “This could affect your treatment down the road,” of course they’re going to say, “Yes, I want to know.” You’ve got to do the whole thing. And we’re really not properly trained to do the whole thing, which is why there is no consensus. We want to do it, but we all know that we don’t really have that alternative.

Neal D. Shore, MD, FACS: And we’re time constrained. Everyone’s time constrained.

Evan Y. Yu, MD: Yes.

Michael A. Carducci, MD, FACP: And the final thing is, we still don’t know what to do with it. Would we change our therapy? Would we do something different? Or are we just on alert? Those are the things that we have to figure, as well.

Evan Y. Yu, MD: That’s why I even said, “Maybe predicted.” We still don’t know. We’re doing the clinical studies right now. We don’t know that they’re definitive predictive biomarkers.

Raoul S. Concepcion, MD, FACS: Isn’t that the term that they use, the genetics people? They call these people “pre-virus.” These are people who are predestined to, if you will, potentially—based upon their genetic testing—have something down the road. But, they haven’t started down the process. It has not been diagnosed. And, again, for some people, that just might be too much from an emotional standpoint—from a psychological standpoint. That’s a heavy load.

Transcript Edited for Clarity