How to treat Prostate Cancer in 2024 with Dr. Rana McKay

Intro Hello everyone I am Rahul Gosain. Speaker 2 And I'm Rohit Gosain. Speaker 1 And we are the oncology brothers. Today, we're thrilled to have a nationally known researcher and a clinician, Dr. Rayna McKay from UC San Diego, to walk us through the current standard of care for prostate cancer. Rayna welcome. Speaker 3 Thank you so much for having me. It's an absolute pleasure to be here with you all. Speaker 2 Thank you so much, Reyna. It was such a pleasure to see you at Gu ASCO and now doing this. Thank you so much for taking the time to do this. Speaker 3 Oh, absolutely. Speaker 2 So diving right in into their prostate cancer algorithm, focusing on the localized disease, I know that radiation and surgery play a huge role here. Current Standard of Care for Prostate Cancer Where do medical oncology take place and how? How do we stand here with that? Speaker 3 You know honestly for localized has disease, low risk localized disease even active surveillance has become a a much more common practice for those Leeson 6 tumors with low PSA and disease confined to the prostate. And you know sometimes medical oncologists are not involved sometimes they can be involved. Certainly in my practice I see a fair bit of individuals as as you're sort of the, the you know, even broker when it comes to this space. Sometimes individuals just want an opinion about their their risk, their risk of a progression in somewhat not through the eyes of a surgeon and not through the eyes of a radiation oncologist. And I think we can definitely play a role in helping facilitate those early discussions. Speaker 1 Right now you've mentioned Gleeson 6. There's been a lot of talk saying should we even call that cancer, but not just low risk, a lot of these patients are getting upstage because of our staging modalities, which brings up the idea of PSMA, PET CT How are you using this and are you using this to stage all your patients up front? Speaker 3 Very, very good question. And actually at Gu Asco this past weekend, there was a heated discussion about whether we should actually change the nomenclature around grade Group One or Gleason 6 cancer. And I don't think, I don't think we have a a overwhelming yes we're going to change but I I know the discussion will continue to be had with regards to utilization of PSMA PET across the spectrum of prostate cancer disease states. For those individuals that have low risk disease or favorable intermediate, I'm I'm not really utilizing PSMA PET, there's really no role for you know use of this modality. I mean the main reason to be getting this is to assess for occult metastases and the likely of likelihood of occult metastases in the low intermediate risk favorable population. It it's it's exceedingly, exceedingly rare, and you're more apt to find false positives that you're chasing your tail around than anything that's clinically meaningful. Speaker 2 Thanks. Now focusing on the high risk where we know that abiradrone in combination with radiation and ATT is approved, what is the exact patient population that you utilize abiradrone role here? Abiradrone in combination with radiation and ATT So very good question. So this data about ADT escalation for those very high risk patients stem from Stampede. And you know that this cohort of patients is not just your classic NCCN high risk, but patients had to have a Gleason 8910 cancer T3 disease or APSA greater than 40 and they needed to meet two out of those 3 criteria. There was no PSMA PET imaging at the time that patients were enrolled onto Stampede with this criteria. But a large subset of these individuals did in fact have a cold metastatic disease. So you know the the Abbey for high risk, it's it's like Abbey for like super, it's like Stampede high risk, very high risk, not just NCCN, you know, for those, yeah. And for those people that are undergoing surgery, you know should man decide that they don't want upfront radiation, they want surgery up front, that is potentially A modality that can be utilized. Though the rates of biochemical recurrence following surgery for individuals with high risk disease is certainly you know higher. And so that's where we employ salvage radiation strategies with or without ADT. Speaker 2 They're moving right along, particularly in the PSA relapse or biochemical recurrence. Enzalutamide Now we have enzalutamide with recent approval as well. So how does that all tie in? Based on the algorithm here right now it's. Speaker 3 A very good question. I think the the space of biochemical recurrent disease, it's like the wild Wild West of prostate cancer because there's so many different things that people can do. And especially now with PSMA PET imaging it's it's just added this additional layer of complexity and it's resulting in treatment decisions that aren't necessarily predicated on level one evidence. You know so there's a there's a lot of heterogeneity that like from the you could watch an individual if they've got a low PSA and slow PSA doubling time. If you know if they've had surgery and they're under and they've recurred, they can obviously get local radiation. But you know if somebody has apsma PET scan and they have spot metastases where you we're seeing just radiation to the metastases without ADT we're seeing radiation to the metastases with ADT. You know there's also the data from embark of escalated ADT for those high risk individuals adding enza to ADT, there's enza monotherapy that was also looked at in that trial trial. So we actually, there's a wide spectrum of all a ton of different options that can potentially be employed and I think a lot of what actually ends up happening is, is really critical on that shared decision making that happens with the patient. Every patient has, you know, different goals and risk benefit kind of, you know, scale that they're weighing about the their approach to their prostate cancer and also understanding the patient's comorbidities, their age, their potential life expectancy. Because you know, many people with biochemical, biochemical recurrent disease, the majority of them don't die of prostate cancer. So I think understanding that helps drive what to do and how aggressive to be. Speaker 1 And again Reno as a community oncologist, all this is so overwhelming, but it is so good to see that there are so many more options now. But it is about the patient that's right in front of us, what's their need, what's important to them when it comes to quality of life and what are the risks versus benefits that we're doing with either combination or single agent ADT or enzyme here. Reyna, any particular scenario where you feel comfortable with Intimate and ADT and also any scenario where you prefer or Localex over other ADT formulations. Speaker 3 So very good question. So in the localized setting, it's the the question isn't really about intermittent ADT. You know for people that present with localized disease that's potentially curable. We're treating them with curative intent with definitive therapy for a finite period of time and then they're going to stop. And I don't want to have to say I'm going to retreat you because I want you to be cured. So I think in the context of localized definitive therapy, the intermittent question doesn't so much come up. It's it's for those people that are recurrent that don't have the option of cure where we talk about intermittent. Now with regards to Religolex, this is a oral GNRH antagonist that results in more dramatic testosterone declines up front and sustained castration. There's also a more rapid time to T recovery after discontinuation of Religolex and there's some, you know, post hoc analysis around cardiovascular events that may suggest there could be a more favorable cardiovascular profile with Relagolix. So that is you know, post hoc, so you have to take it. For what it's worth, where I like using Relagolix is in situations where I am, I am going to intend to give the patient an off period because when they're off therapy you want them to recover their T and and feel well and have improved quality of life. Or in in somebody, even though the data is post hoc, if there are significant cardiovascular risk factors and they really need one ADT, then I may lean towards that agent. You know it's perfect for the short course ADT, you know, four to six months of ADT, four to six months like you're you're done, you give their therapy and and that's it. Yeah. Speaker 2 And particularly for M1 CSPC, if these patients are presenting now with low tumor burden and then the doubling time is not a concern, do you see any role of DOSI, Taxol or making these patients go through such regimented approach there? Intensified therapy for metastatic disease Yeah, very good question. I think first I will say the studies that looked at intensified therapy for metastatic disease, these patients were metastatic by conventional imaging. So what we're not talking about somebody who had apsma PET and has has one or two spots or even four or five spots on PSMA PET, but they're kind of regular CT scan and bone scan is negative. Those people were not captured on those studies. But for people who are overtly metastatic on routine imaging, you know, we've dichotomized by volume of disease, high and low volume utilizing the modified charted criteria with, you know, four more bone mats and presence or absence of of visceral metastases. And then also looked at timing of onset of metastatic disease. Do they have synchronous or metacranis disease? And you you can kind of generate 4 buckets if you will, you know if they're, you know, high volume metacranis synchronous, low volume metacranis synchronous. And and generally, I think for the high volume synchronous patients, those are the patients that I think in my clinical practice, I'm really escalating with triple therapy, ADTARSI dose attacks. All those are the patients that have, you know, the worst prognosis and probably need escalated therapy. I think for on the opposite end of the spectrum is your you know low risk metacranis patient who you know could certainly get by with ADT and an ARSI without any need for dose of Taxol. And you know when we think about the effect size of the ARSI in those low volume attackerness, you know it it's smaller because their risk is lower. So that's sort of how I like to think about integrating dose of Taxol in the MHSPC setting. Speaker 1 And this is also the setting, we've not touched upon this just yet, but looking for germline or other somatic mutations going to be helpful because how are you going to incorporate the PARP benefitors given that we can use them as single agents and now also it's combination? Speaker 3 Yeah, very good question. I think in my practice, you know I do germline testing for patients with you know locally advanced high risk disease, not even metastatic. And then anybody that's metastatic when I first know that they're metastatic they get tested because I like to plan ahead and know what how I'm going to potentially tailor their therapy and also it helps them form discussions around prognosis and cascade testing for family members. So you know at the present time we there is no role for PARP inhibitors in the hormone sensitive setting though there are studies that are currently being conducted and selected patients evaluating that. But we don't have data at the present time for how to integrate. I think largely the data is utilized to help strategize treatment options in the CRPC setting, the castration resistant setting and I think as we talk about that setting we have data from three studies of PARP inhibitors in combination with ARSIS. PARP inhibitors in combination with ARSIS You know, some of the limitations of these studies were that they were predominantly done in patients who had received ADT alone in the MHSPC setting. And we know that in clinical practice now that population though it does still continue to exist, it's decreasing as people are getting escalated in the MHSPC setting. So certainly the labels differ based off of the trials that were done, whether it's Bracha 1-2 mutated or just a panel of HRR genes. But that certainly can be a consideration. And and the great thing is there's actually a lot of other drugs too. You know if they haven't seen Dosi that's an option. You know now we've got you know Pluvicto, Lutetium, PSMA, you know monotherapy, PARP, Cabala, Taxol, Radium 223. Sipulusal T can also be utilized though in clinical practice it's utilizing, it's being utilized a lot lower. I think in my clinical practice where I integrate Sip T is in patients who are having some PSA progression on primary hormone therapy. They're otherwise doing well. You can kind of get in their Sip T over a six to eight week period and then just go on to the next thing you know. Speaker 2 Going to your point about testing for germline, I think doing it much earlier on as you were stating, I think it just confers patients and their families that if it is positive, it opens up more doors for treatment later. So that's a bit comforting now Rayna, outside of Bracha or homologous repeating mutations use of NGS, how do you utilize to guide your treatment or even management? NGS Especially when you have TP53 or P10 or RB loss present, does that dictate you getting scans sooner at all? Speaker 3 Yeah. No, very, very good question. I think there's been excellent work that has been done looking at these you know almost aggressive variant prostate cancer. If there's the presence of one of the three tumor suppressor gene genes that are altered. You know we know that those patients that have such genes particularly RB loss or RB alterations, they are have more aggressive disease. You know maybe in those individuals you're going to want to be integrating chemotherapy. Those tumors sometimes tend to be a little bit more androgen independent or insensitive. So it does certainly help with, you know, strategizing around therapy. I think it's also good to know, you know their mixed status. We know those tumors can be pretty aggressive. You know, 1 to 2% of prostate cancer tumors are MSI high or have high TMB, which could open up the door for pembrolizumab. I think one of the most provocative questions around pembrolizumab is if you know somebody's MSI high, do you wait till they get CRPC before you integrate pembro? I mean I literally just saw somebody yesterday in clinic who who has a, you know, de Novo metastatic disease, they're high, high volume And you know the question is you know, do we do you escalate with pembro in the MHSPC setting, We we don't yet have data, but it's it's you know, we need to figure out answers to these questions because these are the things that come up in real life practice like you just you see that genomic alteration you like, why am I waiting until they progress you know? Speaker 1 So in this case, right now, what are you doing for this patient? Are you using Pembro up front or are you waiting for it? Speaker 3 I'm waiting and using ADT with abiraterone and dose of Taxol as well and waiting for the pembro at a later time point. But I think in the absence of data, I'm hesitant to use it in combination with quad therapy. You know what I mean, but. Speaker 1 Yeah, and it's. Speaker 2 Interesting because especially how amazing responsiveness we've seen in other tumors when especially for MSI high patient population. And just to go, it's just to how important it is to say that NGS testing is extremely important and telling us we do it, we would not find out about any others. And just to stem off from that point, Reyna, are you doing NGS testing on progression at all? NGS testing in clinical setting I know that we were at Fellows Forum, there was a paper presented by one of the fellows who said there is use, but what are you doing in your clinical setting? Speaker 3 I I do like to try to do NGS testing periodically throughout the patient's disease course. A lot of times their first Test is done off of a prostate biopsy may not necessarily reflect what's actually happening with the patient now and and is usually done in a treat in on tissue that's been not exposed to any drugs or therapies. And so if there are problems with doing a repeat biopsy, the patient's got bone predominant disease, lymph nodes really small. I do integrate CTDNA testing though you will sometimes lose the ability to detect certain alterations, particularly gene losses which aren't really captured well on CTDNA tests. And now, you know, there's other drugs being developed. Sorry to interrupt. There's other drugs being developed, you know, AR degraders that are being developed in AR mutated tumors. There's, you know, AKT inhibitors. There's other different classes of drugs, CDK 46 inhibitors, there's. So I think there's a lot of potential for additional targeted therapy strategies that could inform eligibility for clinical trials for patients. So I always try to ensure I have an updated test. Speaker 1 And again, we're not going to go too deep into this topic, but using CTDNA to even monitor the disease that is something that we've used in colon cancer. A lot of different platforms are pushing serial CTDNA to monitor this. Not standard of care, but what we have available right now as a tool scans when these patients have up trending PSA right now. How to monitor PSA in patients with castration resistance Are you getting PSMA PET CT every time you see that or how are you restaging these patients? Speaker 3 No, very good question. I don't necessarily restage with PSMA PET at every imaging juncture. I do think it's important to be continuously staging patients in especially in the castration resistance setting or I should say scanning because their stage isn't really gonna change, but they're getting those scans done. You know sometimes I see all too often that you know treatment decisions are only happening based off of PSA fluctuations alone and a patient may go one or two or three years in the hormone resistant setting without a single scan and all decisions were based off of fluctuations on PSA. And I think that is doing the patients a disservice because I think that could potentially result in stopping a therapy where there could be clinical benefit just because of APSA rise And and we know in the hormone resistant setting PSA is not as informative like Radium 223 for example. PSPSA doesn't help us at all with assessing response nor for CIP T you know So I think I I don't think PSA is the whole story. I think it's the triad of PSA clinical symptoms and imaging that helps a clinician integrate that data to decide do I stop therapy or not. It's not just any one parameter. There's a, you know, integrated thought analysis that happens without stopping or starting a new drug, you know. Speaker 1 Yeah, I know there's so much more to just staring at one number, the clinical picture, the scans. And again coming back to patient centered care, we've talked about PSA as a marker. PSA as a marker Is that a reliable marker when you're giving pavictorial latrician PSMA? Actually where are you using latrician PSMA? What lines? And then are you monitoring PSA or are you waiting for them to complete 4 to 6 cycles to repeat scans? Speaker 3 You know, very good question. So I think everybody is really post an ARSI. Sometimes I will use it concurrently with an ARSI right now predominantly in the post chemotherapy setting, though we know that there's many patients who don't want to do chemotherapy or are not eligible for chemotherapy and so in those scenarios you can consider doing it pre chemotherapy. You know, I think in my practice I tend to follow PSA with each cycle. Every six weeks I do like to get midway scans. If they're doing great, I'll do it after three cycles. If the PSA isn't coming down as fast as I like, or maybe rising, I'll do it after two cycles just to gaze what's actually going on. But I think following people with PSMA Pet even when they're doing Lutetia and PSMA can be challenging because there may be changes in SUV and and other things that we just don't really know what it means. And we've certainly seen flare documented on bone scan and CT scan in the in the context of effective other therapies and we have not yet characterized if that exists with PSMA PET or you know you know if there were to be some sort of flare response or increase in SUV that then resolved. So I think I'm sensitive to kind of making decisions where we don't really have a lot of data. Speaker 1 So just so that I get the sequence right, you usually expose them to dose of Taxol, then consider a Latitium PSMA and then come to Cabazitaxel. Speaker 3 So very good question, I think. Yes, I think initially I think the placement of cabazitaxel in the context of Lutetium hasn't really been totally spelled out. I think in some people who are having sort of rapid progression or visceral metastases, I may do Cabazitaxel first over doing you know Lutetium depending on what I know about their disease. So I think it does vary based off of clinical symptoms. Speaker 2 Oh, wow. With this ever changing field, there's so much to always unpack. Thank you so much Rayna for taking the time to share your thoughts on this treatment algorithm of prostate cancer with us today for our listeners, let's have a quick recap. Outro In this discussion today with Doctor Rayna McCabe from UCSD, we focused on her treatment approach to prostate cancer. We have covered treatment options for localized disease, including the role of Abby Ratarone in high risk patients, along with radiation involvement and surgical involvement. Speaker 1 During this discussion, we also had a chance to reiterate the importance of testing for germline and somatic mutations. Bar pet invaders in selective patients continue to play a big role. Speaker 2 In castration resistance settings, we've focused on systemic treatment options including Dositaxel, Cabazitaxel and Letitia PSMA being available for our patients today. Thank you for tuning in. Make sure to check out our urothelial cancer and RCC treatment algorithm discussion as well. We are the oncology brothers.