Pedro Barata: Thank you, Zach, for having me. It's a pleasure and a very important topic. And with the emergence of PET scanning, we are seeing a lot more of these patient populations. So it's always a very important topic that we face in clinic often.
Zachary Klaassen: Absolutely. I think about this patient as they've had treatment before, possibly radiotherapy, let's say 10 years ago. They come in, they've got several areas on PET scan. How do you start this discussion? And somebody who otherwise feels well, their PSA is going up, they get a PSMA PET scan. How does this conversation about systemic therapy start in your clinic?
Pedro Barata: Yeah, great question. So I think as you mentioned, these are patients who are facing or faced prostate cancer in the past. So it's not the same as you introducing the topic of prostate cancer. Some of these patients were previously treated with surgery, others with radiation therapy and often along with androgen deprivation therapy.
So actually for some of these patients revisiting the concept of lowering testosterone levels, what does that mean? What the word horrible word castration means and we're trying to avoid. And also, can we have different ways or better ways to optimize blocking the androgen signaling pathways? For so many of these patients, we are revisiting those concepts.
So we are introducing that idea. We also introducing, of course, again, as we look at the patient, important to look at factors, patient age versus physiology, cardiovascular disease and the metabolic risk, frailty, baseline functionality, life expectancy. What is the baseline cognitive function? Is there any polypharmacy going on? Are there any important drug-drug interactions? So as I introduced the topic of systemic therapy, I like to think of that and also disease biology. And I'll stop here.
Low volume recurrent disease does not mean always indolent, nice biology. They're not the same thing. And so it's relevant to also bring up the molecular characterization of the tumors along with germline. So somatic and germline testing to be able to get all the factors for us to make the best decisions.
Zachary Klaassen: Yeah, great opening statements. I think when we think about treatment intensification, we could talk about MDT and the role of that and that's a whole probably separate conversation. Just focusing on systemic therapy for years we'd have given this patient ADT alone. They would've gone on, we'd have done intermittent perhaps.
Now we have good data from many trials such as ARASEC, ARANOTE, some of the other trials like TITAN, ENZAMET, et cetera. These low-volume patients do benefit from treatment intensification. So how do you discuss ADT alone versus why we may consider doublet or even not necessarily triplet, but even considering that in the conversation?
Pedro Barata: Yeah, it's a great question. As you said, so the backbone is indeed lowering testosterone level or ADT. And the question is treatment intensification. So you got to balance survival benefit. You know that the addition of ARPI, whether it's darolutamide or another ARPI does provide more tumor control, does provide survival gains. And you have to balance that with the treatment burden.
And that's an important aspect. We mentioned we're describing or we're thinking specific about low-volume, but even the low-volume disease looks a little be different. You can have patients with a high amount of lymphadenopathy head to toes, if you will, versus those patients who perhaps have recurrent few lymph nodes only or with one or two bone metastases. So then the question around what is the tolerability to RPIs? What's the safety profile of the RPIs? They are different.
When we do abiraterone, we are thinking about some adverse events and prednisone that are not necessarily the same as when you're thinking of antiandrogen like darolutamide. When you think about drug-drug interactions, I mentioned before polypharmacy, I'm thinking about what is the baseline cognitive function. We just saw data comparing to antiandrogens, enzalutamide, darolutamide in regards to cognitive function. And then what is this shared decision-making? What are the goals of the patient?
So every time we think of treatment intensification, ADT plus ARPI, I think that's the goal of the game is at the end of the day, prolonged survival. So the simple question I have in my mind is if I forget everything else, is this patient facing mortality from prostate cancer? If the answer is no, from whatever reason that might be, comorbidities, other diseases, et cetera, I'm not thinking about that. The goal of the game is to prevent problems from prostate cancer, but it's not focusing on survival.
So that is perhaps the first question I try to answer in my mind. And then everything else I alluded earlier plays a role. I do have my preference in regarding to the ARPI profile. I've been using a lot less abiraterone because of the exposure to prednisone, because of the efficacy data around the antiandrogens that may be considered a little bit more efficacious, although we lack randomized phase three trial data comparing anti-androgens like darolutamide, enzalutamide, apalutamide to abiraterone. But also the safety profiles can be different.
I care about cardiovascular risk. It's very common in our population with many have metabolic syndrome, just lipidemia. Many are taking many medications like statins, anticoagulation, et cetera. So that profile matters to me as I think about the RPI to use. But that's a way for me to start the conversation with the patients from that perspective.
Zachary Klaassen: It's really just a shared decision-making, isn't it? I think my next question is around additional counseling. So you start these patients on treatment. Again, they probably come in with no symptoms, they're doing well, high-functioning people. How does the conversation go at that six-month visit, the three-month visit, the six-month? They're on systemic therapy, they're probably on doublet therapy. How do you manage their side effect profile during this initial time?
Pedro Barata: Yes, that's a great question because for most of these patients, if you think about recurrent disease, patient was not lost to follow-up. You're probably checking PSA in testosterone levels, you saw some rising PSA, you probably got a PET scan often, more often than not, and you find low-volume disease. So very likely you are facing a patient with relatively low PSA number and it's likely that you're going to bring that PSA number down to undetectable.
So patient's going to be happy from that point of view. And that usually happens within a few months. And we also know that PSA less than 0.2 is also associated with better outcomes. So that's great. So, for the vast majority of the times, you will achieve tumor control within that timeframe. Three, four, six months, nine months.
So the question is, how do you handle? So the conversation can be boring in a sense that, "Okay, doc, numbers are the same. I'm doing okay." But I always bring up about five points that I make sure I address for every single patient. And to me, the five points are blood pressure, glycemia, and those touch a little bit of the cardiovascular. So blood pressure, glycemia. I touch the diet, whether or not they engage in either more important meeting with dietician perhaps, having some education around what to eat, what not to eat. I try to address that because it also helps with the overall metabolic syndrome that many of these patients are diagnosed with.
I also bring up the exercise, particularly muscle strength, which we know it's a problem, muscle loss around low testosterone and is aggravated with RPI. And finally, bone health. And by bone health, I refer to supplementation of calcium vitamin D. We have evaluations with DEXA scan and then we talk about what is the risk of fractures from osteoporosis? Do you have osteoporosis? Do you have osteopenia or not?
So those five factors to me are relevant. I'll make sure I touch base on all of them in addition to never forget to do scans on a regular basis. On trials we did it every three months. I would argue most of us don't do that in clinical practice. We do it less often. I'm still old school, so I still use conventional scans a lot. And I tend to make sure that all my patients have at least every nine to 12 months restaging scans. Why? I don't want to just trust on PSA because we know we can get burned because you can have a prostate cancer go rogue and you have a de-differentiation that will grow with losing the ZIP code from prostate and grow without PSA production without looking at prostate cancer. So making sure I have conventional scans.
So as you apply that logic, those five aspects in clinic every single time, when I have a patient on RPI ADT, I tend to see them every three months unless there's something happening and that changes, of course. They keep me updated as medication for other things change anticoagulation, statins, et cetera, these lipidemic medications, diabetic medication. So it's important for us to know to check drug-drug interactions and addressing those points every three months. And then scans and then DEXA scan.
And for the most part, these are patients that stay in our clinics for a long period of time. I haven't mentioned, but in many times, Zach, we also bring a multidisciplinary approach. And these are patients that often have seen, have engaged with radiation oncology, have considered metastasis-directed therapy. And they also keep checking that sometimes there's specific scans to make sure there's integrity of the bone if that's the case.
For example, MRIs. So those are specific points that come up, but that's kind of what managing these patients may look like in our clinics. They meet dietician, they meet us. They may meet the social worker, financial support, maybe other specialties are urology, radiation, oncology. We already address genetics. So in the case of positive germline, they've met with genetic counseling. And we are basically talking about what may happen and when. So we always revisit the goals of care.
Zachary Klaassen: Fantastic advice, Pedro. I want to close with just practical takeaways for our listeners. We see that the high-volume patients, the discussion's a lot different than these sort of recurrent metachronous patients. What's some practical takeaways for our listeners regarding this specific patient population?
Pedro Barata: Yeah, that's a number of them that I touch base directly or indirectly. Of course, we need to treat the patient, not the disease volume. We cannot be biased by it. It's easy for us to think, "Oh my God, it's aggressive disease because I see a lot of it." High tumor burden we associate to badass cancer. But don't forget, sometimes biology, low-volume disease is not necessarily always indolent disease.
Zachary Klaassen: Sure.
Pedro Barata: So keep that in mind. Treatment intensification for the most part is the default unless we think that the life expectancy from the patient outside prostate cancer is shorter than our ability to control the disease with ADT ARPI. We should not make decisions based on chronologic age alone. So yes, we take that in mind, but we should not say, "You know what? You're 80-year-old, therefore we should not think of ARPI." That's a wrong thought process.
Shared decision-making, I think you touched on that point. I think investing time on this counseling, upfront counseling, why the treatment matters, why we're doing what we're doing, managing the adverse events, and of course, re-assess regularly. Don't lose those patients. Don't trust just PSA.
Zachary Klaassen: Yeah. Well said, Pedro. Always good catching up with you in UroToday. Thanks so much for your time, Pedro.
Pedro Barata: Thank you for having me. Always a pleasure. Thank you, Zach.