How to Treat Prostate Cancer Localized to Advanced Settings - Dr. Scott Tagawa

[MUSIC] We are the oncology brothers. >> Hello and welcome back to the oncology brothers podcast. I'm Rohe Hedgo-Sane, here with my younger brother, Andrew Cahose-Raho-Gosane. As community medical oncologist, we use this platform to touch on recent advances and to reiterate the current standard of care in the world of cancer, so that we can all stay up to date and provide the best care to our patients close to home. Today, our focus is on treatment algorithm for prostate cancer. Rohe Hedgo-Sane has a lot of questions in this space. What staging modality do you rely on? When is PETPSM a the right answer? How do you pick one error PI over another? In what lines are you using Plovickta? How to manage some of the side effects that come along from what we do? To help us walk through early disease, gastric and sensitive and castration resistant prostate cancer and the metastatic disease and to answer all these questions, we're excited to welcome Dr. Scott Tagawa, a two-year medical oncologist from Whale Cornell Medicine. Scott, thank you so much for joining us. Thank you very much for the invitation. Look forward to the discussion. Scott, let's start with localized disease and then we'll build up to get to metastatic settings for low and favorable intermediate risk and localized prostate cancer. We're often talking about active surveillance, surgery or radiation. For that unfavorable intermediate or high-risk disease, ADT becomes more important and now we also have that mature data from stampede with ADT and Aburadirone as the PFS and OS is significant. At six years, that metastatic free survival with Aburadirone and ADT is 82% versus 69%. So this is clearly the standard of care. But Scott, what if the patient has underlined cardiac problems to begin with? Do you consider replacing the other error PI's here for Aburadirone? Like, I literally had this discussion with the patient yesterday, who, let me take us to back, low intermediate, high-risk and the localized part, is now little bit in flux with PSMA PET, as you just mentioned, as well as other risk stratification factors such as gene expression, to know the classifier, through people noted to Cypher. I took the other major one that's out there is using AI to interpret the pathology, MMI from Arterra, I'm sorry if we're saying the brand names, but people know about. Anyway, those all go into the mix to help us shift some of these fields. There isn't in between situations, so literally, I had a patient yesterday that was very close to the stampede virus. So people have to remember that's a very high-risk situation, high-gleason school with high-ish PSA, probably T3N, positivity and pelvic lymph nodes, and that threw me over. So with cardiac disease. So what I said is based upon the stampede trial, more or less, the level one data is with Arterraone, but I need to talk to your cardiologist about how safe that is in terms of the level one evidence, and I could extrapolate, say, I could just say there's a metastatic disease, and then maybe get another ARPI with knowing less of that data. And maybe someone with worse cardiac disease, their combrides are more where some of their prostate cancer, and sometimes they're not even deescalate in terms of number of drugs, even to a shorter course. So, especially with discrepancies, anyway, I agree with you in terms of this kind of an algorithm, but number one, I think it's great that I think you're more than just community not colleges, by the way, but I think it's great that community and colleges are aware of this data, because even for M1, bone scan, positive, and mesetic disease, not everyone's getting more than ADT, and to know in this curative setting that that is an option, I think, is very important. We also over-treat some patients. So, you know, the goal here is cure, potentially. I think that's something that is maybe less of an issue, as long as not at lethal toxicity, but we also have to keep in mind throwing in their luteamide just because they're high risk and I want to escalate. I don't know that that really has a clinical long-term outcome. So, it's a nuanced discussion. I think an important fact is knowing the data, but also treat the patients sitting in front of us, not just following algorithm. Scott, multiple things to tackle here. What you're saying is that we are over-treaten some of these patients, and later during our conversation for MCSP, we'll learn where we are. So, sometimes under-treating some of these patients, especially when we have the triplet combination available. Now, tying in the story of PSMA PET CT, which is rather more sensitive tool where these trials, particularly stampede and others, were done based on conventional imaging. So, we are sort of because of this sensitive tool, diagnosing some of these patients with metastatic disease. However, a lot of it could be also false positive. So, how are you tackling that? Do you go about biopsying these lesions, whether it's rib lesion or vertebral lesion, which is rather oligometastatic disease? And is this a common modality? Are you using for your staging scans? So, let me start with the end. I believe that at least for clinical high risk, besides an MRI of the pelvis, PSMA PET CT is the standard staging modality. So, I call that conventional. I know that's a different term, but I think that is the standard -- right. New standard. Standard of care. Anyway, but using the PET CT when there's something that may be outside the prostate, I'm thinking about the pre-test probability. That's how we help interpret any tests. So, a PSA of 100, the lesion grade group five, I think it's more likely. And then it is a combination of the PET findings, which is largely size and uptick, level amount of uptick. SUVs are not as reliable, because that's also a little bit based on the tracer and the scanner, but, you know, gating by liver or parod or something like that is another -- those ratios. And then on the other component, we don't do PET alone anymore. So, it's either PET CT or pen MRI. It's not going to say diagnostic quality CT or MRI, but there's something that is also there, so having that other part. So, all of that together, and then throw in an expert reader or a second opinion, I think the false positives don't actually turn out to be false positives as often as before, because they'll say there's uptake in this rib, but unlikely to represent prostate cancer. So, it doesn't really turn into be a false positive in terms of the clinician. On the other side, I would say, well, if you enrolled in any of the trials for surgery or radiation, I would not know. No one about that. I'm going to give you the benefit of doubt and treat you, and then we'll figure out kind of done the line. Thanks for covering that. Believe it was a paper from UCSF or UCLA in our conversation with Dr. Ellen Price as well. If one has oligometastatic disease, it is important to do that biopsy to make sure that what you're not dealing with is false positive disease. Now, moon long, we will touch on this modality again if we use this for monitoring or restaging purposes in our CSPC and CRPC state, but in our CSPC state, our biochemical relapse itself, the choices are single agent ADT or ADT plus ARPI, and also single agent and zalutamide. This is based on Embarque study. How are you picking amongst the treatment options here? So, too, I don't get too far in the weeds, but I do want to get this message out there that we've essentially eliminated these terms or looking to eliminate these terms because of patient advocates, the castration we're trying to get rid of. So, APM, Andrew and Pathie Modulator, encompasses ADT, ARPI's, AR degraders, SIP-11, and all those together. And then we have three letters, naive, meaning they haven't received anything sensitive. They received a little bit in the responding, more or less the same bucket, or resistant. So, anyway, in the APM N, naive, I think the first concept of the biochemical recurrence is, are they curable with local salvage there? So, that could be cert, typically, radiation after surgery or ablation or surgery or something like that after radiation, kind of, that's the typical thing. That's the main thing. We don't want to throw away the chance of a cure. For instance, in BARC, they would have either had already local salvage therapy or not been eligible for it. But I do think that it's not something we want to miss because that's another suretive window. Beyond that, I am looking a lot at the prognostic tool that we've had the longest, which is PSA. And there's problems with PSA, but kinetics and absolute value. So, a higher absolute value, quick kinetics, I'm thinking systemic there. Now, I'm not necessarily getting rid of any local therapy, but that's what I'm thinking. We need to get systemic therapy. And those are the patients that we now know have a survival benefit from the embark data. This is whether or not they have a positive piece of a pet or not. You know, they would have had a negative CT bone scan, but to my point is that a single lesion that we think is a true positive, or even biopsy positive, you know, they would have fit in BARC, and it would be reasonable to give them that type of a therapy. Extrapulating based upon other trials, and we've done for a lot of times, a lot of entities in Priced Cancer on the Cancer with Meshastis Structur therapy. I think that's another new one that's there. And, you know, we don't fully have that data. I would say the available data says that Met Directive Therapy versus Nothing improves time to events. Adding systemic therapy to Met Directive Therapy improves upon Met Directive Therapy. Those are overall concepts across. trials that I think are there. And then we found the patient. Some patients would say, you know, I would take living shorter to have longer with testosterone. So then there's the patient's care questions there. And I do my best to guide based upon the prognostic factors, such as PSA double the time. And you briefly touched on this salvage, your heart, because the intent here is cure. We're all just coming back from GUSCO 2026. We also saw data from Poseidon study, a large meta-analysis there looking at the role of ADT after adjuvant or salvage radiation. And what we're walking away with is if your PS is really low, not everyone needs ADT. So something to keep in mind. This is also a good place where we often rely on that intermittent ADT stop and go approach instead of exposing all our patients for long-term ADT. Okay, now moving on to that metastatic APM sensitive prostate cancer. Scott here, this standard is no longer ADT alone. Road T touched on this as well. We need to add air PI to ADT or even add chemotherapy as well. But then we are also seeing data from Plevicto and these settings based on PSMA adjuvant study. And we also have Nerapereb with Eberraderon here for a Braka positive disease. Scott, can you touch on our treatment options here? The data in hand, and how are you picking one over the other? I think it's important and you already said this, I'm going to re-emphasize. I think it's very important that almost everyone should have at least ADT plus an ARPI and not everyone's even getting that. There's a poster that I can't call because I didn't have a chance to really digest it. But I know from social media you might have covered it actually that even in patients with comorbidities, there's an advantage to that ARPI doublet. Obviously, that was the rest of the respective study and those patients in the doctor and patients mind were able to tolerate it. But anyway, I think we should do that. We don't know I would say with any good evidence that anything else improves overall survival. Even in the Levant disease rating prostate, in this era, I would say that's not 100% level one. Triplets, I think, with a dose of taxil, the classic triplet, I certainly do that. High volume, de novo, metastatic disease. But I do not know that dose of taxil adds anything in that setting. That's why we have two North American trials, US and Canada, asking either immediate use or if the later after six months, if the PSA doesn't need or get less than 0.2. So, anyway, we don't know that is clear. But that I'd say would be a standard out there. Broca 2, we know, is number one, a porpoirnosc, number two, a pretty good predictive factor for parpinipers way more than even rock a one. So, I'm not shocked actually that the FDA approval is very specifically for Broca 2. It doesn't mean that there's never going to be an expansion of those genes. But I would say that is prime time to me. But we don't know. If we don't test germline and somatic, we're not going to know. But I'd say that is a subset that is prime time. The rest, we don't know, you know, p10, interestingly that signature I also might predict or prognoscate for dose of taxil. But we might have an AKTM and then the bigger bucket in terms of biomarkers is PSMA. A lot of new ones says I don't have time to really get into the weeds with PSMA addition. But the methodology where there was a PSMA pit after most had an ADT and even some AARPI, which I might have modulated that scan. But most are positive. We know that and most of the time that we know that because it's the staging modality. And that may be an FDA approved option. I'm not personally using off label right now. I think we should have additional overall survival data later this year. And I think that will be quite useful as well as the peer reviewed publication. So I wouldn't say that's today, but that is a potential for the future. All right, Scott, I'm going to hone in this further, but I just want to reiterate Rahul, what you mentioned, Niraperab did get approved here in December 2025. And that that is for Bracket, two positive disease. And that just continues to reiterate the importance of germline and somatic testing. Now tying in the radio ligand, what we saw from GUSCO 2020 update from PSMA addition, where quality of life was preserved when using Plovicto here. Scott, if this was to get approved, where would Plovicto sit in your treatment landscape, whether would that be for a metastatic CSPC space, or you'll reserve that for CRPC? So, so there's a there's a bucket of patients that I'm going to say to myself. I'm a little bit worried about a triplet, you know, maybe those people that were thinking of even AVT alone, I like to mention that to every single patient, so I'm less internally biased, otherwise I will do it more. And then, you know, certainly get the patient's wishes. But in that setting, because not every Bracket 2, am I going to say, okay, you need to take Niraper now, but most is going to be there. I think the biggest question is going to be in the triplet is not the Bracket 2, because we'll probably go to the parvin inhibitor and there may be more partners in the future. It's going to be dosy or lutition PSMA 617. And that is not really so different than in the PSMA 4 space. So, we'll see our PI where we're thinking about chemo versus lutitium. I think it's going to be a similar type of a decision, which is really clinical at this time, more visceral symptomatic zee, and healthy, I'm thinking of chemotherapy, not that they can't respond to lutitium PSMA 617, but that's what I'm thinking of chemotherapy. And then those that I want to push back chemotherapy may be do something, because we don't have a, we have a little bit of head to head data, but not a lot, and certainly not in the setting of chemo versus lutitium PSMA 7. But in terms of the quality of life, I would say it's very similar. Actually, all three drugs, dosy, Niraperive, and PSMA 7 are very similar in terms of quality life using fact P, where in the first several months, it's a little bit lower. We know from charted it was lower, and then for what Mike Morris presented at SQG 2026, it was a little bit lower initially, this is a fact B total, but then it cut up. So once they're done with that part, or we've instituted support of care, adjusted the Niraperive dose, then the important thing is that it's equal, you know, more or less versus the control, but just talk about PSMA addition for EQ5D and BPI short, that was basically the same thing throughout. So despite the fact that there are more AEs for all of these, anytime we add another drug, there's always going to be more AEs, the patient where outcomes don't appear to be significant worse, but we have to acknowledge that at the beginning, as we're adjusting things, that may be an issue or which we have to figure out for lutitium PSMA 617, how many cycles should we give? Right. The meds go away on PET. There might be micromets, XZs, but are we then treating more of the prodded and the intestine and kidney than we are the tumor? Endite. Now there. Actually, can I just, sorry, can I just push a little right here as well? Because I think this is a good segue even in that castration-resistant disease. I know you alluded to the staff PSMA 4 versus PSMA addition. We're using that clinical patient in front of us to make that decision. How and where are you using plevictotray in that castration-resistant disease? Also, how are you monitoring that disease when someone's on radio-likeance? Your CT conventional imaging, PET PSMA is PSA a good marker? Can you expand a little more in the castration-resistant disease as well, Scott? Yeah, it's not so different in any setting. I'm going to, and we automatically have PSAs, but I'm also probably not going to only use PSAs. That's just going to be something that is there. What I tend to do, or we tend to do as a center, we tend to get specs after every dose in every single setting, and we can do that the same day. What we do is four hours later, if it's hard for them to travel, I often will see them the next week, just clinically, and a day eight, see, spec is good for any PSMA-positive organ. So it's gone from the other organs, but we still use that, and they don't necessarily have to come back the next day, although that's the biggest data set. So I will have that kind of, it's not a cheat, but I'm looking at that as an image. But into your more directly answering question, I don't rely on PSMA imaging alone, because what I also, it's no different than treating with radium and scanning. I want to get a CT. I'm looking at, is there anything growing that I'm not treating? So I'll have this back to have some idea of typically, especially for later stages, after cycle two is typically what I'm going to scan them, you know, around that time point, and that doesn't matter if they're getting chemotherapy, anything else, before three months, I'm going to be getting a scan, and that generally includes when they're on the tissue, 6.1.7. I may or may not get a PET CT at that time, but because I've had the specs. So if I'm confident, they're still pretty positive for PSMA, I just want to make sure there's nothing that's growing that I'm not seeing on the spec. It may be just a CT. Sometimes I'm getting a bone scan, because that's what I'm going to follow longer, but that's only for a different type of a reason. So I will always periodically do that on an average, it's every two cycles, every three months or so, and I'm using it to both make the decision to give more or not to give more, and I take the reasons not to give more either, because they're clearly progressing. You know, the vision, situation when they have nothing else, maybe I'll go a little longer, but earlier when they have choices, if they're progressing, I'm going to stop. I'll typically give them at least two cycles to kind of, that fair chance, but maybe they're going to go to something else, or if they're having a really good response. I might stop or pause, doesn't mean I'm not ever going to restart. Sometimes this after two, sometimes after two, three or four, I usually do employ the pet there because that's more sensitive than the spectra. I just want to make sure there's nothing else to kind of consolidate within the other cycle. But those are the situations where short of stopping for toxicity, either very good response or progression other reason I'm stopping. We haven't yet proven that stopping after real good response is better. It just makes sense. Although there is semi-level one data because the randomized trials from Australian New Zealand all include therapy. The first study versus vasotaxle, seven out of 98, wherever stopped because of a complete response by PSA inspect. When you have multiple of these options available, one has to tie in the side effect profile, patient-shed decision making process with with Pobicdo. One has to worry about dry mouth, sideopinias, bone marrow suppression and same thing for parp inhibitors as well. But Scott with Abbey Ratro and one has to tie in the cardiac comorbidities and control diabetes, ties in with the prednisone that gets combined here. But for Enzalutamide, Appalutamide, Darylutamide, which are approved in CRPC as well as CSPC space, are you deciding amongst these lutamides when you cannot give Abbey Ratro? So when I can't give Abbey Ratro that's usually a comorbidity issue. We don't have great head data. We have a little bit of end-toversistarodata, but we don't have a lot of great data. So I would say that Enzalutamide is technically as well tolerated as anything else. But when I'm choosing one of these on purpose, it's comorbidities and a lot of times comorbidities or other drugs are out there and I'm looking at drug-droid interactions. I'd say the blanket statement is Darylutamide have a little bit less, but it's different. So those are the things that I'm looking at. And then there's subtle other issues like twice a day versus once a day. There looks to be across trials, like differences, more rash versus more fall risk. And then there's cost, you know, I think it's good for all of us to think about costs to society, et cetera, but especially out of pocket costs. All right. Just before we close, one last question. Scott, in your clinical practice, when are you adding carboplatin in these refractory settings after lutitium, if you scheme otherapy, parpinobitor is in now you're planning to rely on cabazetaxe by itself or doublet while you add carboplatin is it NGS as a detumer burden? What's the right clinical settings? So it's a combination of genomics and clinical factors. So rapidly progressing livermets, big bulky tumor in the pelvis, independent of, let's say tumor suppressor gene loss, at least discussing a doublet with a platinum drug. I think we're even more informed with genomics there, unclear in a post harp inhibitor setting, like with other diseases, how well that works, although I still certainly discuss it. A lot of times there's space in between. And in prostate cancer, it's not only reversion mutation. So it's not the exact same as ovarian breast cancer. But anyway, I use a combination of clinical factors plus genomics right now in terms of genomics. I would say it is tumor suppressor gene loss would be the biggest bucket. We have covered a lot here. Scott, thank you so much for walking us through your current treatment paradigm for prostate cancer. For those sitting in, let's go over a quick recap from today's discussion. In this treatment algorithm episode with Dr. Scott Tagawa, we have covered prostate cancer. Up front and localized disease, we reiterated that ADT plus aberad run is the crunstandard of care for high risk disease given improved PFS and OSC in stamp data. Also post radical prostatectomy, let's not forget salvage radiation. If we start to see that PSA rise from Poseidon meta analysis, we can also appreciate that not everyone needs ADT with adjuvant or salvage radiation. Roat, your tea takeaways here in APM sensitive prostate cancer space. Right, Rahul, if one does see metastatic disease, we should jump on germline testing because we have a pool of neuroparib here, though not approved yet, but we are seeing Lutitian PSMA make its way based on PSMA addition study into CSBC space as well. Currently, Lutitian PSMA is approved in metastatic CRPC. With this, we have to worry about the dry mouth and bone marrow suppression. Rahul, what do you want to add here? Yeah, we're also here. We also talked through our available data with parpenebitters. We tend to see most of the response with Brachatum mutation. Not all homologous repair gene mutations derive the same benefit. This is important to keep in mind because again, we're balancing side effects with efficacy. If you have questions around what scans we should use in prostate cancer, how do we sequence our available options? This episode is for you. Thanks for tuning in. See you in our next discussion. We are the oncology brothers.