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Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined on UroToday by Dr. Pedro Barata, who is a medical oncologist at the Seidman Cancer Institute in Cleveland, Ohio. Pedro, thanks for joining us, as always, on UroToday.

Pedro Barata: Of course. Thanks for having me. I'm really excited to have this conversation with you.

Zachary Klaassen: I'm excited for this one too. We're going to be talking specifically about your biomarker testing implementation program at your Cancer Center. So just to bring our listeners up to speed on the importance of this topic, can you explain why biomarker testing is so important?

Pedro Barata: Yeah. It's a great question. So we talk all the time about biomarker testing and genetic testing in metastatic prostate cancer. Just to break down, we're really talking about two types of testing. One, the genes you were born with we call them germline testing. It doesn't matter when you do it. You do it once, and you're done.

It's recommended to have the conversation around germline testing for localized, high risk, recurrent or metastatic disease. The second part of the testing, we call it somatic testing, where you're looking after the tissue, genomic alterations of interest. Those might include DNA alterations or RNA alterations or even the protein level.

You can do it in the tissue level. We do it tissue testing, whether it's fresh tissue, or a biopsy, or surgery, a surgical specimen that's seated in the pathology department, archival tissue. Or you can also do a liquid biopsy. And you're looking for circulating free DNA. You hope that translates into circulating tumor DNA, although that's not necessarily 100% there.

With that said, and by the way, the last point is for somatic testing, it appears that liquid biopsy tends to have high concordance rates compared to tissue testing. So that's why we do it. And we do it for many different reasons. We do it because first of all, it provides prognostic and predictive value.

So prognostic meaning you can have better informed conversations with your patients about what is likely going to happen independent of the treatments you bring on board, based on the genomic alterations that you found. That's prognostic. Predictive because you can open the door to a set of therapies that you would not use if the patient were not to have that specific marker. So there's a predictive value there. Things like immunotherapy or targeted therapies like PARP inhibitors are the classical examples of the second part or the second value.

Finally, you have the opportunity to diagnose familial or hereditary syndromes. And with that, we have to talk about cascade testing. If you identify a genomic alterations that runs in the family, you can impact not only your patient in front of you but also his family. And from that perspective, you have that value, that component that you can address by doing those types of testing. So in short, that's what it comes to mind when we think of germline and somatic testing.

Zachary Klaassen: Great summary. So I want to pivot now to you. You've been very instrumental in and setting up the program at your center. Maybe just tell us about that program, how it came about.

Pedro Barata: Sure. Great question. So actually, I should say I like the idea of copying good ideas and not reinvent the wheel when we don't have to. So actually, during my time at Tulane, I work a lot with Dr. Sartor, Oliver Sartor, which is a well-respected expert in the world of prostate cancer.

And there, we're able to have a program where we had a model, that we're able to improve and increase the rate of genetic testing done for our patients there. It was a model that really worked really nicely. Tulane had kind of a smaller environment that you wait.

So when I moved to University Hospital Seidman here in Cleveland, I thought of bringing the model with me. And that involved building a database but also having someone helping us out in the clinic, getting access to those tests in the form of all the portals. So we got access to all the portals. We have this person working with us.

So with that, we were able, in the first year, to increase over 300% genetic testing rates at our center. Now of course, there are always regional differences, right? So UH is a large organization. We have multiple places where we actually go to. So how do you scale that up? That's a good question, right?

And the other one is we also work with our friends and colleagues at the Cleveland Clinic. And can we actually put together a program that basically attaches on the UH system and the clinic system. So with that in mind, we're actually working on that. We have hands on. We're trying to basically scale up the program that started in the main campus and went to one of the academic hubs. We're trying to expand that to touch more hubs out of the UH, as well as trying to implement that at the clinic as well.

We just got good news that I think it's going to happen. So we're already testing it out. So the program does work. And we're at the phase two, I guess, which is kind of scaling it up and see how efficient we are with that scaling. And what does that mean for the community doctors within our own organization? What does that mean in terms of can we get together with the clinic to talk about the difficult cases, perhaps help accessing patients to genomic-based therapies? So that's what we're working on right now. We're very excited to do that or to bring that to the region of Cleveland.

Zachary Klaassen: That's fantastic. And a 300% improvement is excellent. Let's look at just, since you've implemented that program, what have you seen in terms of better treatment selection, patient outcomes, what the patients are telling you. What's your experience been during that time?

Pedro Barata: Yeah. So the first thing we need to know is having expectations about how often you're expecting to see alterations and do something about them is very important. So for example, homologous recombinational repair gene defects, which are biomarkers or predict response to target therapies like PARP inhibitors, you're not expecting to see them 100% of the times.

In roughly one out of four patients, we're going to have that, right? What that means is you're going to test for patients. Only one were going to have that. So if you test the first three and you don't detect anything, don't be discouraged. The same with immunotherapy. Only 2, 3, 4%, you'll identify microsatellite instability or mismatch repair defect tumors.

So that means you need to test 100 patients to find your two, three, or four patients. So if you tested 80 and you didn't find it, that doesn't mean they don't exist. It's just moderate your expectation about when are you going to find that. And then, of course, you need to start looking at other things like TP53 alterations, or RB1 alterations, or PTEN loss because they provide you value, prognostic value, but also, they might give you an idea about who's going to be the patient suitable for chemo intensification.
So understanding what you're expecting to see. So by the way, genomic alterations are found in over 70% of the times, but not all of them are targetable. Meaning not all of them, you're going to actually going to treat them differently, and that's important concept to get. The second is you have to find a model that works for you.

So for us, it was very hard in our model to ask the nurses to work with us to test everyone in a busy clinic of 25 patients that I have in a day. So it's easier to have someone with me that can go in the room, get the consent, make sure the patient go to the lab, have the kits in place, send them out, and then follow up with the portals, right?

Even before the communication between the genomic companies and the EMR that we have at UH. Because even if that's embedded, that's never perfect, right? It never happens the way you really like it. So we found that having this person pulling those reports back to us and then actually getting us a weekly report is super helpful to bridge that gap. So for us, that work that way.
And so and the last thing I'm going to say is there's a delay time between you start testing a lot more, finding the patients, and actually do something about it in terms of treatment. So let's think about it. We test everyone with metastatic prostate cancer for germline and somatic testing.

But as we've talked before here with you, Zach, a lot of these patients are going to still be offered a combo with an ARPI or even triple therapy. And that might work for many years. So that means even if you found a patient who have, let's say, BRCA1 mutation, you might use a PARP inhibitor at the time of CRPC, which might happen two years later, for example.

So what that means is even though you find that result now, you're only going to act on it from the predictive piece, from the treatment piece, two years later. So there's a delay time. Then you got to wait between you testing more until actually, the treatment landscape changes for that particular individual in front of you.

So if you know those things, I think it helps managing expectations. It helps your conversations in clinical practice and also helps you to understand how does the data show. So for us, we increase the rate of genetic testing. We are increasing slowly the rate of use of genomic-based therapies for the last piece of what I just walked through.

Zachary Klaassen: That's fantastic. I love how you highlighted there's a point person that really is in charge of making sure all this works together. I think that's a great take home point. Pedro, anything we haven't touched on about your program that you want to share with our listeners?

Pedro Barata: No. So this is an effort for the large area of Cleveland. We put together a consortium here in Cleveland with our friends from the clinic, and we're really partners in this, right? I mean, it's great to have different shops in town because that elevates the care. But I'm really proud to think that working with other academic centers, in this case, in the Cleveland area, I'm proud because it increases the quality of the care we provide to the patients who come to see us.

And really, I think this can be used in other areas of the country perhaps, where we can actually come up with projects that are really important for the different academic centers with all those regional differences and local differences.

So I'm happy to do this. I'm hoping to come back to give you a great update about it. And the next step on this model or project is going to be how can we help the community docs, that when they get the BRCA, we are also working on bridging that gap there in a sense of saying, hey, here's what we're doing for that patient. Here are the therapies we have available. Here are the studies we have available.

So we're working with the EMR, for example, to get a flag. Every time there's an HR-altered gene within the organization. So we can actually come together, even though we are physically separated. So that's really what we're working on. We're excited about that. I hope to have good news soon.

Zachary Klaassen: That's great. Congratulations on a great program, implementing it, and definitely, we'll take you up on it. We'll have you back on to talk about this in the future. Thanks so much, Pedro.

Pedro Barata: That's a deal. Thank you so much.