Daniel George, MD, on Precision Medicine Approaches in APC: Part 1

Daniel George, MD, Duke University, Professor of Medicine, Medical Oncology; Medical Oncologist, Duke Cancer Center discusses precision medicine approaches in APC with David Ambinder, MD, Urology Resident at New York Medical College/Westchester Medical Center.

This is the first in a two-part conversation with Dr. George. Watch part two of this discussion to learn more about medicine approaches in APC.

David Ambinder, MD: So with that in mind, what we’re going to talk about a little bit today, is genomic markers and how we use somatic tumor markers to guide our patient care, and where we’re going in the future.

Daniel George, MD: It’s really a quiet revolution going on, is the way I would put it, in prostate cancer. For really forever, we’ve thought about prostate cancer as one disease, as a disease that is essentially driven by the androgen receptor pathway, and that’s it. And that has essentially been the biology of early, middle and late prostate cancer, and how we think about the disease. And it’s still there. I don’t want to make it sound like that’s gone away.

But I think what we’ve done to realize now is that there’s a really a tremendous amount of additional genetic variability in this disease. We knew it was there, we just didn’t know what to do with it. And now with some of the characterizations that we have, we’re beginning to see precision medicine emerge. And I think you’re going to continue to see that.

What’s interesting about the genomic profiling is really two things. One is that this is something that appears early in the disease. So, we think about prostate cancer in the natural history of being in some cases 10 or 15 or even 20 years of disease, progression over time, and yet the genetic alterations present in the prostatectomy or prostate biopsies really are the blueprint of what’s going to emerge over time in that disease, in the majority of cases. There are truncal alterations that happen, there are branch alterations that happen, but these truncal alterations, these things that happen at the very base of the formation of this disease, are really critical to how that cancer’s going to behave over time.

David Ambinder, MD: My second question would be, how do you counsel your patients about discussing the these genetic variants that we find, or genomic markers, in terms of how we tell them about what they should be doing in terms of their family? Should they be also getting tested for these?

Daniel George, MD: I think some people take this in a little bit of a stepwise approach, and I think that’s reasonable for early disease. There’s a lot of patients with early localized prostate cancer that we could do active surveillance on, or we could do a limited monotherapy, really definitive therapy, where that’s surgery or radiation, and for these patients, I feel pretty comfortable. We could do that definitive treatment, and if they don’t relapse, that may be all they need.

Now, if they have a strong family history of prostate cancer, or say breast, ovarian or pancreatic cancer, then I’m still going to want to profile those patients. And when I say profile, we’re going to do germline and somatic profiling in those patients. But for patients who don’t have a really significant family history of cancer, and those particular cancers, and have relatively organ-confined lower, intermediate risk disease, I’m fine, not profiling those patients until this evidence of relapse or spread.

But for the majority of patients I see as a medical oncologist, they’re more either locally advanced or they’re metastatic. And for these patients, David, these are the patients that we absolutely don’t want to miss a genetic alteration. And we would like to know that early, for precisely the reason you said, because it may have relevance to family members right then and there, in terms of screening, in terms of other malignancies, in terms of even management of people who have prostate cancer. I’ve diagnosed mutations in one patient, and they’ve gone and talked to their brother who’s had prostate cancer longer than them, and checked, and they have mutations. And if I hadn’t checked in the first patient, the second patient might not have ever known. So I think those kinds of things. It’s still becoming systematic in our approach. Right now, it’s still check this patient at an individual time. And what I’m hoping we emerge to is more of a systematic approach, where we routinely or reflexively test patients when they hit a certain point in the disease progression.

David Ambinder, MD: Sure. So in terms of systematic checking, I don’t think you can remove cancer diagnosis, let’s say specifically prostate cancer diagnosis, and anxiety and cancer-related patient worry. What are some resources that you give to your patients, or have your patients set up with, to deal with some of those things, with let’s say a germline testing that’s positive?

Daniel George, MD: Yes. Yes. So, this is a really important point that you bring up, and that’s really the patient anxiety around all of this testing, and what does it mean, and the implications?

First thing, I think the greatest anxiety is not knowing. And even if you don’t discuss it with your patient, they may find out, they may read about, they may be thinking about, is that relevant to me or not? So, this isn’t the thing we can just ignore now. We do have to assume that all of these patients have some access to information around us, and addressing it proactively with those patients. If it’s somebody I’m not testing and explaining why, if it’s somebody I’m testing in, explaining why this information’s going to help them, it’s going to help them really understand more about their cancer. And not knowing is really the worst case.

And then when somebody comes back positive for a genetic alteration, and if that’s somatic, I reassure them that it’s somatic. It’s not something that they inherited, it’s not something that they’re going to pass on. So that’s another great peace of mind for people. And so, be being able to address that upfront and put that into context is so key. And that’s why I like to check both germline and somatic at the same time, so that I can address both those issues with patients right away. And if it turns out to be something that is germline, that is something that could be related to the family members, again, I find this reassuring. I didn’t cause this, they didn’t cause this. The worst case scenario is not knowing it. So knowing it gives us the knowledge and power to be able to educate all the other family members, to see who, if any, have it, and if they do, which ones, and to be able to then proactively use that inform to screen, or even prophylaxis patients accordingly.

So, knowledge is power. And I try to explain that to patients, and give them the comfort, to say, “We’re going to walk you through all of this.” Now, I’m lucky at a place like Duke where we have genetic counselors, we have molecular tumor boards. We have resources of experts around me that I can easily tap into. But those resources are available out there as well in other communities. It may take a referral to an academic medical center if you don’t have that in your own practice, but it’s well worth it to do that for these patients. They’ll be grateful to you and loyal to you for doing that, and recognize that you were the one to diagnose and really help manage this problem, not just for them, but for their loved ones.