HSPC: Navigating Risk and Management
Transcript: HSPC expert panel
Bertrand Tombal, MD, PhD; Andrew J. Armstrong, MD, ScM, FACP; Alicia Morgans, MD, MPH; Daniel George, MD
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- So, hi, hello everybody. Welcome back for this short discussion with our panel of expert, Dr Andrew Armstrong, Dr Alicia Morgans, and Dr Daniel George. So right away I'm gonna jump on to you, Andrew, and maybe discuss a little bit about, you know, the topic of the moment, the non-metastatic hormone-sensitive prostate cancer with biochemical recurrence after local therapy. There is a lot of discussion about under or over treatment. So what would be your must do around the patient before you start deciding to treat them and how, what is the basic step?
- Thank you, Bertrand. I think that's a really important question to start with because you have to realize that biochemical recurrence is still a setting where we treat with curative intent and we don't wanna miss the opportunity for a second shot on goal. For example, after radical prostatectomy, many men can have successful salvage radiation, early salvage radiation, and see remissions that are durable. And we know that early treatment matters, the lower the PSA level at the time of salvage radiation, the better the outcomes. But there's also overtreatment where we see patients, for example, with very low PSA doubling times, with indolent disease receiving hormonal therapy perhaps prematurely. And many of these patients are elderly. They have comorbidities, they have preferences that may speak against the need for systemic therapy. So I think there's important risk stratification. We want to avoid, for example, PSMA PET scans to justify the withholding of early salvage radiation where the PSMA-PET is very uninformative, for example. The PSMA-PET is not very helpful, for example, at a PSA level of like 0.1, 0.2, where cures are very high in that early salvage setting. So for BCR patients who have already failed salvage radiation, for example, and have a rapid doubling time, I think that's where the higher mortality rate is faced in our patients. And that's where systemic therapy and intermittent therapy is really imperative.
- Because one of the constant after when the patient has a prostatectomy, we will always say, and I agree, that they have a second chance of curative treatment under salvage radiotherapy for, would you say the same if they started with radiotherapy? So meaning, after all, it's a quarter of the EMBARK patients. We do not discuss a lot about these, but do you really believe that if they had radiotherapy to start with, for I mean unfavorable, intermediate or good prognostic high risk, do we need also to consider more local treatment in those with favorable characteristics?
- I think that's another great question. Just a conversation I had just yesterday with a patient. And you know, a common conversation I hear from urologists is that, you know, you can't do surgery after radiation, but you can do surgery, you can do radiation after surgery, for example. And the second shot on goal for a curative intent after radiation might be further radiation, for example, to pelvic lymph nodes, a common place of local regional recurrence. The patterns of spread on PSMA-PET, for example, after radiation versus prostatectomy are different. And so the methods by which you treat local regional disease may differ. And so I think there is a second shot at cure post-radiation. The definitions of relapse and BCR are different. We use the Phoenix criteria, so nadir plus two for radiation, you know, any rise, you know, sequentially from zero or if they have PSA persistence, any sequential rise is how we define recurrence after radical prostatectomy, with lower PSAs being better for early salvage radiation. So I think the PSMA-PET is helpful for post-radiation decision making. You know, you have patients with non-metastatic hormone sensitive disease that have truly a local recurrence and that seems to be a less common pattern versus regional disease, versus distant disease. And the EMBARK data really did not integrate MDT or multi metastases directed therapy, but, you know, as an opportunity to use intermittent therapy as a short course of hormonal therapy, but with radiation, offers patients a way to get off their systemic therapy and enjoy quality life free of systemic therapy.
- And a last question I've got for you is, you already mentioned, it's about PET-PSMA. So in Europe we use it a lot, you know, to everybody, and we tend to redesign the care pathway based on the result of the PET-PSMA. And actually, as you know, there's a lot of enthusiasts who are, for example, metastatic targeted therapy in patient with I would say one or two metastatic deposit on PET-PSMA after surgery. But we now have randomized phase 3 evidence for selected patient with very short PSA doubling time, with high PSA, these patient, they need the addition of an AR pathway inhibitor . So do you think that based on our short experience and because a PSMA show oligometastatic deposit, we should actually try to delay the incorporation the ARPI? Or do we need to study or do we need to take both because that that's a discussion we have on a regular basis in Europe?
- I think it's another great question. There tends to be two independent lines of work here. Those that favor the MDT approach and those that favor the, you know, systemic therapy with the ADT ARPI, which has created level one overall survival evidence in this setting, I tend to mash these two approaches up together where the goal is to get patients on level one evidence therapy to improve their survival, but then to get them off that therapy and have them enjoy a very long treatment holiday with the EMBARK regimen, you know, particularly the doublet therapy, the break tends to only be about a year and a half to two years. So while that's great, most men do relapse and MDT offers patients that opportunity to perhaps have a longer break in other, you know, trials like ORIOLE or STOMP or EXTEND or RADIOSA, there's a whole litany of acronym trials of MDT showing you can extend that duration of therapy off. And so I do like that approach for the oligometastatic PSMA positive setting, and EMBARK-like patients tend to be metastatic if you look at the studies that have done PSMA-PET in those high-risk BCR patients, about 80% have either N1 or M1 disease.
- Thank you so much. I'm now gonna move to you, Alicia, and we gonna discuss about the multidisciplinary team, because I remember a time where the MDT was me or the radiation oncologist when I wanted radiation oncology or me and the medical oncologist, when I believe that the patient needed chemotherapy or something else. But that's not the way we should work today. What are the practical strategy to develop a team where everybody has a meaningful role to play? So what would be the minimal requirement? And let's focus only on hormone-sensitive prostate cancer. Don't go further away. We need to be there, what should we do to be sure that they're all bringing their expertise?
- Yeah, I think ideally it helps when there are actual either in-person or virtual tumor boards where people can get together and discuss patients because then of course, everybody's voice is in the room. But this is hard to do. I think in many European clinics, this seems to be something that is actually integrated into quality guidelines. And so seems to be something that's achievable in those places when it is a priority. I think in many places in the United States, when new patients come in, they can have this multidisciplinary board, which is again, the best way, easiest way to have everybody's voice at the table. But in practical terms, if somebody's been followed by the urologist and now has a recurrence, it actually is an active step like you're saying to bring in the medical oncologist maybe if you don't have that review board. And I think the way that we achieve that in my practice is that we're all in the same space, and so we can all kind of get together in the hall between patients and say, hey, this guy I've been following, his PSA is coming up. I'm gonna loop you in. And at least when that happens in our setting, the urologist will bring in the radiation oncologist and the medical oncologist and we all get together and talk either again, virtually, or in person if we happen to do it in the hallway. These things are hard though, they have to be prioritized. And if we don't prioritize them, it can be really just the urologist or just the radiation oncologist who's making the choice. So knowing your colleagues, making it a priority, having everyone's contact information and having that space to gather, I think, can be the best way to overcome those barriers.
- But you know, indeed for us in Europe, I mean it's some country at least it's quite easy because it's obligatory by law to have a minimal set of physician. But more and more what we realize is, for instance, the need of incorporating people from nuclear medicine.
- Yes.
- Because PET-PSMA has become central to the management of this patient, later, PSMA lutetium is becoming one of the central treatment and we realize that by far we are incapable of looking at a PET-PSMA. So do you think that we should make an effort not just to rely on protocol, but bring these very important colleagues in to get the nuance we need some time to manage some of these patient?
- Absolutely, I think that nuclear medicine is so tricky. I learned something just last week when I thought it was wonderful that I look at all my own scans and I tried to read them, I was reminded that there are tricks that the nuclear medicine team, those docs have when they can just adjust the amount of uptake and I guess the brightness essentially so they can view things very differently. And if it's set at a certain level, when I'm looking at it, I may or may not be even aware that that is upregulated or downregulated. It's not the truth or what I wanna see, and I'm sure I'm explaining this poorly, but the expertise of a nuclear medicine doctor is absolutely critical. And I don't think that our integration of other team members should stop with nuclear medicine, nursing as well as dietary nutrition team members, physical therapists, our nurse practitioners and physicians assistants in the United States and expert colleagues, pharmacists can all be really critical members of the MDT as we're trying to figure out how to add medications and how to optimize the outcomes for patients. So of course, nuclear medicine and all the others as well.
- And do you really believe that this should be one single MDT will review all the case that basically what we do, we spend two hours, three hours every week reviewing all the cases. How do we structure it based on stage cancer and feed, define a core group which has to be there from scratch to the end and add different specialties?
- I think the latter, the one that you talked about second, where there was sort of a structured integration of people as their time and expertise was needed makes more sense. You know, all of the physical therapists and nutrition, dietician and nursing support may be more in patients who have more advanced disease, whereas patients who have early relapse or localized disease may not need all of that support, nuclear medicine obviously now across the spectrum, radiation may be at different points as well, but I think that ensuring that we optimize everyone's time is also critical because we never have enough of that. And when different members can come and go and be integrated as needed, it does make it more efficient.
- Thank you so much. So far, we spoken about indication, about who should be in the MDT, but there is finally the most important person we haven't spoken about. It's the patient itself. So Daniel, how should we deal with this patient? Because, you know, it's getting more and more complex. They go on AI, they go on ChatGPT, whatever, they go on Comet and they coming. So what is the most important, how do we prioritize the conversation with the patient? You've done all this beautiful work on discrete choice experiment, trying to understand what they value the most, how should we incorporate that into first, the discussion with each individual patient and then, very difficult, I've been fighting for 25 years and I mean, I didn't succeed. How do we bring the patient voice into the MDT decision-making progress?
- Well, Bertrand, I thought you were gonna say I was the most important person, but I appreciate that. No, it is the patient. And the truth is that, you know, we can't lose sight of that. We are in a crisis of trust right now in healthcare because patients have have so many sources of information to touch on and they can lose trust very quickly if we don't continue to establish that, right from our first visit, but then throughout, and the way we maintain and grow that trust is by listening to the patient, by asking them questions, by paying attention to them and helping them realize that we have their interests at heart and that we have knowledge that pertains specifically to them, that we can personalize the information to their situation. And although maybe ChatGPT can do that, it's only as good as the questions you ask it. And they aren't physicians, they aren't oncologists, they don't have the background and information. We have to ask the questions the right way. So it's really important for them to recognize that all of these tools are really helpful as supplements, as adjuncts and complimentary sources. But they don't replace the relationship between the oncologist, urologic oncologists, radiation oncologists, medical oncologist, doesn't matter, the oncologist and the patient. and we have to really lean in and value that relationship. We have to continue to establish it with patients by listening, by understanding what their values are. There's discrete, you know, analysis that we did around patient preference are really, really important because we think we know what the patients value the most, but it's not always true. For instance, we found that overall survival, which I think most oncologists will agree, is a very, very important endpoint, is not the only endpoint, although it's the most important endpoint for patients, they're willing to sacrifice some overall survival benefit in order to have quality of life, particularly quality life around certain side effects, nausea, which we don't always think about as a bad side effect. Chronic nausea is horrible for patients, much worse than fatigue. And so it's important to recognize that their experiences really matter and the only way we can personalize our recommendations is to understand their particular situation, what they're experiencing and what matters most to them.
- No, that's very important. A few years ago we had the proposal by the cancer plan to even offer the possibility to some patient joining the MDT and seeing around all discussion. And the first thing is that it make us uncomfortable, but I think at some point they have to be part of this discussion. But thank you for that comment. And finally, I've got a question, I mean, that's more like a practical question, but.
- Can I just comment something on.
- Yeah, sure, sure, sure.
- Is very important, what you said about having the patient participate in the MDT. I just wanna clarify that patients shouldn't be up against a panel. Okay, that's gonna make them very, very uncomfortable and imbalanced. And it's important for patients to realize that they're gonna have one primary oncologist, and again, it doesn't matter the specialty, but somebody, and it can change over the course of their journey. It doesn't have to be set. But at any one time, there should be one primary oncologist that's overseeing that particular aspect of their care at that time and that they're getting their information from, because if there isn't, they're gonna hear competing voices. Even two oncologists, medical oncologists will say things differently. It's so important for patients to have that clarity. I tell patients when you're seeing me, I'm representing the multidisciplinary team and that view and I have all of their information behind me and that they have that, they can go and see one of these people separately from me and they frequently do when I refer them. So it's important for people to realize that they're not just seeing one doctor, they're seeing a team, but at any one time, it's one physician that they're really communicating with. and we have to represent that consensus voice.
- That I fully agree, that's why that experience was never pursued, because but you know, we are living at a time where I understand patients say, I would like to be part of the discussion, I would like to be there. And it's up to you, to us to explain that we need also some confidentiality to discuss between us because we gonna come with a proposal, but we may not agree all of the team that this is the one we would do if we would do it alone. And that's the beauty of MDT. and the final question is, I mean, if you set up space and time to discuss, it's okay, the first step, it's very important. But you think also that we should, in order to improve our practice, we should collect the information and from time to time, we should come back and look what we have decided and maybe compare it to a kind of naive interpretation of what would the guideline says. Do you think that it's good to do MDT, but we should absolutely collect a minimum set of information. You remember, Dan, we worked with ICHOM a few years ago. We tried to do these, a minimal data set to be collected. Do you believe that it was a good idea? Yes, we had it, so it was a good idea, but do you believe it was a good idea and we should really collect that information, a little bit like you do in Ironman, to then build up on this evidence and build new and stronger practice. What's your opinion, the three of you?
- 100%, I'll start, you know, Bertrand, we do not do quality assessments enough in cancer, right? We do a lot around, you know, our guidelines and maybe guidelines compliance, but that's not necessarily quality. There's so many other aspects to the care than just what treatment you select and how you do it and all the supportive care, all the preventive care that's necessary, all the counseling, all the monitoring for, you know, complications and things. There's so much into what we would call quality care that ICHOM was able to identify, that we haven't necessarily implemented in a regular basis because I wanna be good, right? I wanna be perfect and I know I'm not and so I'm missing some things. One of the ways I balance that is to have our patients see our nurse practitioners or APPs because they will catch things, they will talk to the patients, they'll ask questions that I don't ask and the patient may give information back that they're uncomfortable telling me. And so it's really important that, you know, part of this team and Alicia touched on it, it means a lot of different pharmacists, other people use that with the patient. They may have sort of one physician visit, but all these other pieces can really help to complete the care and make sure we're not missing these pieces. But completely agree with you, with EMRs today and everything, there should be ways to do more quality assessments of the care we're given and to do it, you know, not to be critical, but to improve over time. and I think that's really the goal.
- Alicia, Andrew, something to add on this?
- Yeah, I completely agree. I think that one of the important things about the ICHOM initiative was also that it was not just what treatment the patient received, what outcomes, and actually it included some quality of life metrics as well. It also included a lot of information to help you understand the case mix. So what that means is really the complexity of the patient, the comorbidities of the patient, the other competing factors that may affect the outcome. Because if we simply look at the treatment delivered and the patient outcome, we're going to misunderstand, I think, all of the factors that underlie and contribute to that outcome. And so that's a really critical part and it does take resources, it takes time and again, it takes that effort, dedication just the same way that it takes when we try to construct and have these multidisciplinary teams. And when that is prioritized, as Dan said, we can use that information to look back and move forward in a way that makes more sense and is built on data, not just we think this is better, it truly is better for our patients for this case mix. And I think it is very important and hopefully we'll be integrated more into our systems so that we can improve.
- Andrew.
- This has been a great discussion and I appreciate the patient voice being at the center of this. I do want to point out there is a BCR working group that just published guidelines on data collection and risk stratification. And there's a lot more there than the simple data sets. You know, the patient is at the center of that working group. Comorbidities, patient preferences, risk stratification, genetics, imaging data. You know, there's a wealth of data that we now employ in practice but don't capture in our registries or trials. So I think that's a great white paper to refer people to as they're building the next generation of studies.
- So gentlemen, thank you, and Alicia, thank you for this very nice discussion. Thank you so much for being with me and see you later. Bye-bye.
- Thank you.
- Thank you.
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