Alicia Morgans: Hi. My name is Alicia Morgans and I'm an Associate Professor of Medicine at Northwestern University in Chicago, in the United States. I'm so excited to have here with me today, a friend and colleague, Dr. Jason Hafron, who is an Associate Professor of Urology at the William Beaumont School of Medicine and he's here to talk with us about operationalizing genomic testing in clinical practice for patients with prostate cancer. This has been one of the more challenging nuts to crack, I think in our clinical endeavors in the last couple of years, but it's definitely something that we all need to do. Jason, thank you so much for taking the time.

Jason Hafron: Thank you so much, Alicia, for having us, it's really an honor to be part of this program on UroToday. without UroToday, I wouldn't be so up to date, and I check my email every day, seeing what the latest updates and all the great interviews you've done with the principal investigators really is really tremendous work, and thank you for everything you do.

Alicia Morgans: Oh, well thank you for saying that. You're going to make me blush, but in the meantime, we can get on to you telling us some other stuff: Telling us how you really think about getting genomic and genetic testing into your workflow for patients with prostate cancer. Jason, where do things start? How do you get things going?

Jason Hafron: Yeah, I think that it's not as easy as it sounds. We understand the data, we see the benefits of the PARPs in all these great trials we've had. But actually, where the rubber meets the road, getting clinicians to actually apply the technology is a challenge. I'm a part of a LUGPA practice. We're 60 urologists, so to get everybody on the same page, to get everybody using the technology, the key really is clinical pathways. Prostate cancer is moving so quickly. We have trials coming, major category one trials coming out almost every six months, and the way that we implement them, that we speed up the process and get the care to the patients is we really, really work hard on our pathways.

Alicia Morgans: When you say pathways, what do you mean for those of us who don't necessarily have those integrated? And do those relate to treatments? Do they relate to patient selection? What exactly do you mean?

Jason Hafron: Yeah, it's a great question. It's everything. It's the proper evaluation of the patient, as well as the therapeutic interventions. We're a private practice group, community urologists, and we basically translate the NCCN guidelines that are used, established guidelines from various societies and we translate that back into clinical practice. Guidelines are essentially options for treatment based on a hierarchy of quality of the data, but there's a disconnect between the practicality of how do you apply these guidelines and use them in everyday practice? There'll be a group of us, we meet regularly and if there's a new paper or a known update to the NCCN, we will adjust our pathway. We have pathways that are essentially living documents that we tailor and update regularly to incorporate these new technologies.

I think a big difference is, what's the difference between a guideline and a pathway? People think, oh, they're the same thing it's in the guidelines. But a guideline is really what you could do. Here are the options for intervention, here are the options for evaluation. A pathway is this is what you should or must be doing when evaluating or treating these patients. It's that taking this complicated guideline and just saying from what you could do, to what you should be doing when you see the patient in that space.

Alicia Morgans: And that's really interesting and we can get into clinicians and how they interpret pathways. I remember hearing from different clinicians over the years about wanting to maintain autonomy and these kinds of things. But maybe you can comment on this now. In many cases, for most patients, even for those of us who want to maintain autonomy or those who are really interested in clinical trials or doing things differently, for most, those patients, even for people like that, those patients are treated on a specific, pretty regimented and systematic way. Or if they're not, we really should be doing that in many cases to ensure the highest standards and the optimal outcomes for patients. And that's why I would think that you have pathways so you don't forget things essentially. Is that true?

Jason Hafron: Yeah, everything's so complex and moving so quickly, we shoot for 80% pathway adherence. You're never going to get a 100%, there's going to be nuances for every patient, but if we can maintain close to 80% pathway adherence, we think it's a good job. We try to minimize heterogeneity within the care. Whether they see me or they see you or they see my partner on the other side of town, based on the guidelines, these patients should be treated essentially the same, especially in the first, second, or third-line therapies. It does get a little confusing, especially when you're going to fourth-line or late-stage treatment. That's when clinical trials become important, but that also should be part of the pathways. Those patients should be referred for a clinical trial when they meet certain criteria. I think physicians want to be autonomous, they want to think on their own, but in reality, we want to standardize care where every patient's treated the same based on the NCCN guidelines, which is the highest quality data that we have to follow.

Alicia Morgans: I think that's a really important point that in order to get the best outcomes, it's really important that we follow the best data and humans can forget, or they can make mistakes and pathways can help be a good reminder. And so to get back to the prostate cancer pathways that you have developed around genetics and genomics, take me through a general journey for a patient. A new patient comes in, metastatic hormone-sensitive disease. What are you thinking about when you're accounting for that patient when it comes to genetic testing?

Jason Hafron: We're big proponents of genetic testing and we try to get somatic and germline testing right upfront. We encourage both germline and somatic. A lot of people think it's one or the other, we've kind of taken a different approach. We want to get both. There are benefits and there are pitfalls to each of them. But right when we think of anyone who has serious prostate cancer, potentially lethal prostate cancer, we want to get their germline and somatic testing done right away.

Alicia Morgans: And how do you go about doing that? Say the patient's de novo metastatic and then we can talk about a patient with high-risk localized disease.

Jason Hafron: Yeah, we just essentially order the testing and it's in our pathway. I think the key with the pathway in getting back to it, is that we monitor, we have third party software that will check to make sure that that testing was done. We work very closely with the third party germline testing companies and the somatic testing companies and they give us back the data to see what tests were ordered. And we look at it and if something was missed, we have nurse navigators and data analytics that will flag that chart. The next time the patient comes in, this patient needs somatic testing. This patient needs tissue testing, whatever it is, someone else is checking that chart to make sure that that pathway was met. And the reality is we're so busy. We're forced to see so many patients, our philosophy is we need to develop better systems and better pathways to make our doctors better doctors. And you can't really do it sometimes in a clinic where you're required to see so many patients. We focus on creating these safety networks or these pathways so that our doctors can do the highest quality of care.

Alicia Morgans: I think one of the most important things, whether your practice has pathways or does not, is ensuring that there's that safety net. And however those are constructed and pathways are a great way to use the EMR, to use technology to support us. And I think probably that's the way we all should be going in the future because it takes it out of the human memory domain. But if that's not where your practice is, maybe having a nurse who owns genetic testing and who keeps a list of everything and when that patient comes back in, hey, is that test back? Is it not back? And integrating that into the EMR is going to be important. However we do it, having those checks and balances is critical. And so for these metastatic patients, it sounds like you're meeting this person, new de novo metastatic disease, you are sending both germline and somatic. And what happens when you see a patient with say high-risk, localized disease, you're planning to do definitive therapy to the prostate to try to cure this person. Are you doing any testing for that patient?

Jason Hafron: Yeah, we've kind of moved in that direction. And we're moving in a direction where we're testing at least germline in these patients, even independent of family history. With the recent changes in Medicare reimbursement for even just BRCA1 and BRCA2 testing, we had just implemented the pathway just a few weeks ago. It's very early in our curve but I think the high-risk localized, yes, definitely, they need to be screened. But we're even moving towards similar to where the breast cancer surgeons have gone. Is that anyone with a diagnosis of prostate cancer, we are moving towards screening them for BRCA1 and BRCA2 testing. I look at breast cancer as a group that's typically a few years ahead of us in prostate cancer and I try to model our pathways or our disease management similar to what they've done in their field.

Alicia Morgans: Really, really interesting and important. Some good comments about making sure you understand the insurance reimbursements in your area, but this seems to be moving earlier and earlier for many patients. And right now, since as you mentioned, the NCCN guidelines recommend germline genetic testing for any patient with high-risk and very high-risk localized disease and as you mentioned, this is outside of family history. No family history required. That's going to be really important. And just to reiterate, that's also important for metastatic patients. Germline testing is recommended regardless of family history. If a patient says, "Oh, I don't have any relatives that have had prostate cancer." You should never stop there. That metastatic patient actually deserves to at least consider whether he wants to have germline genetic testing. And also remember, of course, that patients can have family members who have ovarian or breast cancer because these are things that run in that cancer syndrome. Always good to remind our patients.

Just one more final question on one of the other points that you made that was really important that for metastatic patients, in particular, you are not settling on just germline, you're not settling on just somatic. And as the guidelines suggest, you're testing both because you can actually have half of the mutations that we find and actually find that are targetable are going to be in germline and the other half are going to be in somatic tissue. How do you implement those? You say you order the test. Are there specific tests you order? Are you sending tissue? Are you sending circulating tumor DNA? Liquid biopsies? How are you doing this?

Jason Hafron: Yeah. And it's just a major paradigm shift for urology because historically if we saw enlarged lymph nodes on a scan, we just assume they're metastatic and just start therapy. And it's been a challenge or work to get urologists to say, "That lymph node needs to be biopsied." Why do I need to biopsy that lymph node? You need a biopsy it because there's important tissue or potentially somatic mutations that can affect the patient's therapy. We instituted that every metastatic patient needs to have tissue testing. We start, if there are lymph nodes available, we will go for those.

We don't do such a great job with bone. We work in multiple centers and our bone yield has been pretty low. We don't have that specialized interventional radiology or processing that a lot of academic centers have. But then if we can't get fresh tissue, we go to archival tissue that's available. Most of us have done the biopsies on these patients so it's usually available. And if that's negative, then we'll go to circulating tumor DNA. But we have that established, this is step one, step two, step three. Once a patient's metastatic CRPC, we need to get this tissue because based on the recent trials, this can have a significant impact on this patient's disease.

Alicia Morgans: I love to hear you say that, but it's just music to a medical oncologist's ears. We always say, "Tissue is the issue." And those lymph nodes, they could be lymphoma. They could be who knows what? Inflammation. They could be lots of things. We've seen, I'm sure you've once in a while seen, that what you biopsy is not always what you expect it will be because imaging isn't 100% clear and the gold standard is really to get that tissue and then you can use that same tissue to send for sequencing. I love that and I'm really impressed and proud of your practice and glad that we're all coming together on this. Any final thoughts or recommendations that you have to folks who are trying to get this into their practice, get this genomic genetic testing standardized in their practices.

Jason Hafron: I think it goes back to how we initially opened. I think practices need to sit down together, the experts in the practice, and develop these pathways. These aren't developed overnight, they're living documents that take time and I don't think you can really rely on urologists to implement these new technologies. I think it really takes that's the tool or the pathway because otherwise you're relying on the urologist to do his or her own research or to base it on their anecdotal evidence and that's not effective. I think pathways, it's not complicated. It's very straightforward to do, but it just takes that time outside of the clinic, on a night or weekend to put these together and then continue to work towards them.

Alicia Morgans: Well, I would wholeheartedly agree. And I would also say that it's not just the urologists who can use some help with this. Medical oncologists, I think, and other providers probably can use this too. Whenever something is algorithmic, whenever it's part of the system, it takes that ability to forget outside of the human hands of the doc or the clinician who's trying to take care of that patient. And it just removes that one layer of potentially missing something. However we can take care of our patients best is what we should always do and really systematizing this is something that will make everyone do better, and all patients I think really have the opportunity to have access to things that could really transform their outcomes. Thank you so much for taking the time to talk with me about this today.

Jason Hafron: Thank you.