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Dr. Alicia Morgans: Hi, and welcome to The ASCO Post Roundtable Series on Novel Hormonal Therapies for Prostate Cancer. My name is Alicia Morgans, and I'm a GU medical oncologist and Associate Professor of Medicine at Dana-Farber Cancer Institute. Joining me today are two of my friends and colleagues, Dr. David VanderWeele and Dr. Neeraj Agarwal, Dr. VanderWeele?
Dr. David VanderWeele: Hi. David VanderWeele, GU medical oncologist at Robert H. Lurie Cancer Center at Northwestern University in Chicago, medical oncologist focusing especially on prostate cancer.
Dr .Morgans: Great. Thank you. And Dr. Agarwal.
Dr. Neeraj Agarwal: Hi. My name is Neeraj Agarwal. I'm a Professor of Medicine and Director of Genital Uterine Oncology Program at the Huntsman Cancer Institute, University of Utah. So pleased to be here.
Dr. Morgans: Thank you both for being here. Today we will be discussing recent updates in prostate cancer and integrating these new developments into three patient case studies. Our final installment will focus on locally-advanced high-risk prostate cancer.
Mr. HS is a 57-year-old man with a history of hypertension, who presented to his urologist with increasing nocturia symptoms. His PSA was 12.4, and an MRI was performed that demonstrated a PI-RADS 5 lesion in the right apex, concerning for prostate cancer. He underwent a prostate biopsy that demonstrated Gleason 4+4, grade group 4 prostate adenocarcinoma.
What are the next steps in the workup of this patient with high-risk disease? Dr. Agarwal?
Dr. Agarwal: I'll definitely go with functional imaging. Of course, conventional imaging are part of workups, CT scan and bone scan. But when they are negative, but if they are negative, definitely PSMA PET scan has a definite role here. I'll go ahead with the PSMA PET scan.
Dr. Morgans: Wonderful. And that is actually, of course, what happened to this patient. He underwent a PSMA PET, and this demonstrated several retroperitoneal lymph node metastases. So Dr. VanderWeele, what do you think your next steps would be in workup and treatment for this patient with locally-advanced high-risk prostate cancer who's now been appropriately staged?
Dr. VanderWeele: Now we begin the treatment discussions, and basically, I think the backbone of treatment for a patient with locally advanced disease, and especially with lymph node involvement, is going to be radiation plus hormonal therapy, meaning androgen deprivation. And since there's lymph node involvement, then it's going to be intensifying that hormone therapy in some way.
I think the strength of that data comes from STAMPEDE trial, so intensifying therapy with abiraterone and prednisone would be the way to go. That data would support it even for patients without lymph node involvement, if they have two of three high-risk features. I think we're in the eligibility criteria for STAMPEDE: a PSA greater than 40, T3 or T4, and grade group 4 or higher. But if you have lymph node involvement, then that kind of satisfies the criteria, and that's what I would discuss with this patient. Talking about hormonal therapy and radiation and then discussion about all the side effects that come with those therapies.
Dr. Morgans: Great. Very, very important. And actually, this patient did discuss that with the team considered treatment with radiation plus ADT and two years of abiraterone acetate and prednisone per that STAMPEDE trial.
As we consider, just trying to understand not only the risk of this patient, but potentially the risk for his family, is germline genetic testing something that you would integrate into your thought process, Dr. Agarwal, for a patient with high-risk localized disease?
Dr. Agarwal: Yes. Technically, this patient does have prostate cancer beyond prostate. We saw multiple retroperitoneal lymph nodes being affected by prostate cancer. There's no doubt that, in my view, that patient qualifies for germline testing per multiple guidelines.
Germline testing has been a problem compared to somatic testing, which we used to order in our clinic, right there. For germline testing, we had to refer patients to high-risk clinic, to genetic counselors. Especially during the pandemic, I used to see quite an attrition of patients who were asked to go and see a genetic counselor, but they did not follow up on that suggestion. And we have gotten around that by actually ordering germline testing as well as somatic testing within the clinic when patients are here. If they are found to have any of the germline mutations which are deleterious, which are considered inherited, it actually drives the patient to go and see the genetic counselor. All those challenges, but we think we have gotten around those challenges.
Dr. Morgans: That is really fantastic advice and ways to help encourage our patients who are eligible for germline testing to get that testing. Certainly, if we find something on somatic testing, like a BRCA2 alteration, the most common thing that we will find in these patients, that can be something that helps stimulate patients to move forward.
I have had some patients who had concerns around germline testing and then the potential implications. One thing that I've also found and would just like to make a shout-out to the team that's running this is that the PROMISE Prostate Registry, which is an online registry available to any patient who has high-risk localized or locally-advanced nodal involvement, like this patient, or metastatic disease, these patients are able to actually get germline genetic testing through that PROMISE Prostate Cancer Registry online for free. The genetic counseling is then also included for patients who are identified as having a pathogenic germline mutation.
Really a way to give them control. It's outside of the health-care setting, or at least it's sort of adjacent to the health-care setting, so there may be less discomfort from a patient perspective in terms of that information getting out to insurers or other folks. But it gives them that control, and they do their own home testing. And we know that it is a legitimate, certified testing group that is doing this. This is run through a grant that our colleagues at Johns Hopkins and University of Washington are championing, and it's really a wonderful resource for patients. Glad to make that comment, and thank you for your suggestions and guidance there too, Dr. Agarwal.
In this patient's case, important that we did do this testing. This patient was found to have a germline BRCA2 alteration. Again, the most common thing that we will see in germline testing for our prostate cancer patients, but certainly something that needs to be considered, if not now in terms of his therapeutic decision-making, perhaps in the future should this cancer come back become metastatic.
In terms of moving on to next steps, we've discussed that this patient, as Dr. VanderWeele suggested, it's going to be getting intensified therapy with ADT and abiraterone for 2 years in the setting of definitive therapy with local radiation. When you're thinking about this treatment approach, this is a multimodal approach, Dr. VanderWeele, what are your considerations in terms of complications during treatment, particularly the systemic treatment? And how do you really work to mitigate and deal with those?
Dr. VanderWeele: Yeah, so it's a discussion with a patient that these are going to, this hormonal therapy is going to cause things that he is going to experience, like loss of libido, fatigue, hot flashes. But we also need to be mindful of things that he is not going to experience, but may affect his overall health, especially components of metabolic syndrome, poor glucose control, tendency to have increased blood pressure, or increased risk of cardiac events.
It's important to have those conversations. It's important to make sure that the patient is engaged. Well, I'm not an internist, at least in my practice, so try to make sure that they are engaged with their primary care doctor. If they have more significant risk factors, that may be making sure that they are engaged with a cardiologist or that they maybe make a referral to a cardiologist if they need to.
I guess in my practice, I often will manage blood pressure initially and adding on an agent or sometimes even two, if needed. That's not all that unusual with abiraterone. But depending on how many agents they're already on or how difficult it is to control, we'll definitely call in help, either from the primary care doctor or, if it's, again, depending on the number of cardiac risk factors, with a cardiologist. Yeah, we do have a cardio-oncology, clinic at our cancer center. We're blessed to have that and work well with them. But not everywhere has that, so acknowledging that.
Just talking about lifestyle changes, I emphasize a more vegetarian-like diet, less fried foods, and just in general talk about sort of a healthier diet and ways that you can find things that are acceptable to the patient. The best diet change is one that they can adhere to. So some discussions around that.
And then also exercise, whether you have an exercise program that you can refer patients to or just discussions about exercise. Both cardio as well as resistance training really go a long way in trying to mitigate the toxicities, both in terms of the metabolic syndrome, but also the other side effects that come with it, like sarcopenia and stuff and fatigue.
So it's a more lengthy discussion and sort of a thoughtful approach to making sure that we're addressing all these things the best that we can. Often it's a multidisciplinary, often and optimally, a multidisciplinary approach.
Dr. Morgans: Absolutely. Well, I certainly aim for the same approach in my clinic. Thank you for walking us through that. That's very, very helpful.
Dr. Agarwal, would love to hear any other, anything else that you do there, but also what your thoughts are in terms of this patient, who hopefully will be cured of his locally-advanced disease with this definitive radiation and the long-term ADT that he's getting. Do you have thoughts about how to counsel him in terms of when treatment ends and what he can look forward to, if anything, in terms of treatment cessation and how he moves forward after that?
Dr. Agarwal: David raised so many important points, and I will not repeat any of them. Just to put things in perspective, as far as the longevity is concerned in this patient, in the STAMPEDE trial, adding abiraterone of 2 years, increased metastasis-free survival at 6 years from 69% to 82%, meaning we are talking about decades of survival, even if the patients are not cured. We are still looking at a decade or more of survival. That's number one.
And second is in younger men, who are developing these cancers, locally-advanced cancers, and who are going to be living decades with their diagnosis. Even though they're cured, they are living with the long recovery of testosterone. One of the most important request I have, or I wouldn't call it demands. None of our, most of our patients never say, "It's my demand." He say, "Doctor, tell me how can I get my testosterone back as soon as possible after you finish this treatment?"
That is for so many reasons. These are younger men with their younger spouse. They want to have normal physical, sexual, psychological lives. And it is so important for them to have their testosterone back after we complete treatment of this short duration. So beyond cardiovascular health, which issues which can emerge after decades of living with low testosterone, we are also dealing with emotional and psychological issues in our patients. That makes it so important to achieve a rapid testosterone recovery in our patients.
In this context, I think I again see a increasing role of GnRH antagonist from that perspective. Using degarelix, using relugolix definitely allows my patients to rapidly recover their testosterone versus GnRH agonist like leuprolide.
Those are the additional points I wanted to make.
Dr. Morgans: Well, thank you for that. I think in the context especially, this is a 57-year-old man. This patient's very focused on moving on to the next stage of life, which is still a life that may involve relatively young children or a life that often would include work still in this younger patient population, where they want to have that lack of fatigue. They want to have that vitality, get-up-and-go, and of course, libido is important to patients in some cases regardless of age. This can be important at any time. So allowing patients to move on after their treatment is finished, I think, is a really, really important goal and part of helping them to feel well and to stay well. Thank you for talking us through that. Are there any final comments that you wanted to make Dr. VanderWeele as we wrap up?
Dr. VanderWeele: I guess just one comment about the case. The patient had really metastatic disease on molecular imaging, so it's RP nodes, not just pelvic nodes. But all of our data on treatment algorithms is historically, the vast majority of it is based on conventional imaging. I would just make the point that I wouldn't deny the patient curative-intent therapy as we discuss in this case, despite what's lighting up on the molecular imaging is a little bit further afield. But really, for sure, these patients were included in STAMPEDE. That's how I would proceed, and with curative-intent therapy as we discussed here. Otherwise, agree with everything that Dr. Agarwal said.
Dr. Morgans: Great. Thank you, Dr. VanderWeele. Anything you wanted to add, Dr. Agarwal?
Dr. Agarwal: No. Quality of life is so much more important as our patients are living much longer, for decades.
Dr. Morgans: Wonderful. Well, one thing I would like to add is that this patient had a germline BRCA2. So we do have to make sure that this patient is aware that this is something that could be present in siblings as well as in his children. It's something that may warrant cascade testing if those relatives exist. And it certainly warrants a discussion around that. Please, as we're taking care of these patients, do remember to take care of their families as well.
Now we'll get to key clinical takeaways. Germline genetic testing is recommended for all patients with high-risk, very high-risk, and locally-advanced prostate cancer in addition to those patients with metastatic disease. And that's regardless of age or family history.
Intensified treatment with ADT and abiraterone acetate for 2 years is associated with prolonged metastasis-free survival for very high-risk localized or locally-advanced prostate cancer. We did hear a discussion of what some of those high-risk features are, as we're helping to choose which patients may benefit or may have that discussion around intensified therapy in this setting.
Intensified hormonal treatment may be associated with additional cardiovascular risk, including hypertension and fluid retention. So do think about that with treatment with abiraterone. Monitor the patient and ensure that we deal with those complications should they arise.
Use of the GnRH antagonist relugolix is expected to be associated with faster testosterone recovery after treatment cessation than the GnRH agonist leuprolide. So also something to keep in mind as we are expecting that this patient will have a treatment-free interval, hopefully for many, many years, but at least of some duration.
This brings us to the end of the case. Please see the other segments for further discussion about the latest data in prostate cancer or visit ASCOpost.com.