Dr. Higano: Hello. Welcome to The ASCO Post Roundtable Series on Updates in Prostate Cancer. I'm Dr. Tia Higano. I'm an adjunct professor at the University of British Columbia, formerly at the University of Washington, and joining me today are two of my colleagues.
Dr. Graff: Thank you, Tia. I'm Julie Graff. I'm a medical oncologist at the Knight Cancer Institute, OHSU, and also at the VA in Portland.
Dr. Shore: Hi everybody and it's great to be with both Tia and Julie. I'm Neal Shore. I'm the chief medical officer for GenesisCare in the US for urology and surgical oncology. And I'm the medical director for the Carolina Urologic Research Center in Myrtle Beach, South Carolina.
Dr. Higano: Great, thank you both. Today we'll be discussing recent updates in prostate cancer and trying to integrate these new developments in four patient case studies. Our first case will focus on treatment of an elderly patient with a metastatic hormone-sensitive prostate cancer.
So this is a real-life case of mine. He's an 88-year-old man who had a history of localized prostate cancer. He was diagnosed in 2017 with a T1c Gleason 4+3 pathology with a PSA of 16.38. Before we go on, Neal, you're the urologist here. What is your thinking about that and now that we're using Gleason group for consideration, what's your thinking on this patient?
Dr. Shore: Well, it's such an interesting case because at 88 that he had even a PSA checked and the USPSTF would say, "Stop checking." And there are other guidelines that would say "Stop checking." I've never really agreed with that. I think the importance is that patient/physician in important shared decision-making conversation. And there's 88 years old patients of ours, here we're talking prostate cancer but women too, who have performance status that's very, very good and may have actuarial survivals that are very, very strong depending upon not only their overall health, their comorbidities, but their family histories. Did their mother and father live into their late 90s or even into the 100s. And I see many patients now, I live in a retirement community where 88 is like the new 68.
Dr. Higano: Exactly. Yes and actually all the comments you made about this gentleman are true. In fact, one of his more recent professions was as a personal trainer.
But he also has his own ideas. He decided to go with SBRT as primary therapy at the end of 2017, which certainly would've been an outlier in that era. Two years later, those PSA increased from the nadir of 2.7 to 4.71. And at the time, the imaging technology that he had led to fluciclovine PET scan that showed three bone lesions that were new. He was very adamant that he did not want to have androgen deprivation therapy because of the known side effects that he and especially his wife had read about extensively. And so chose to be treated with SBRT again to those three bone lesions.
One year later, maybe go to the next slide here. The PSA increased from the nadir 2.7 to 4.68. And the PET scan again showed another three new lesions, but the old ones that had been treated before were quiescent. So he had SBRT to those three lesions, but then only eight months later his PSA rose to 8.89, and he had new hip pain, which of course he denied being related to prostate cancer. But the PET this time actually showed uptake in the right acetabulum that was likely related to his hip pain and three other lesions. So the patient says he went back to his old thing. "I'm not going to have any more ADT or any ADT. I'm worried about what it's going to do." So confronted with this type of thinking Julie, what do you have in mind?
Dr. Graff: First I think it's so important to listen to your patients and what matters to them. So I'm glad that discussion was had. Secondly, as a medical oncologist watching all the new studies come up over the years, I feel more and more strongly that systemic treatment is what really helps people live longer. At the same time they can appreciate that it can decrease some important functions in life including the ability to have sex for many of these guys. It also could put people at higher risk of heart disease and diabetes and weight gain, etc. So for him, I would talk to him about his previous treatments with radiation to these metastatic lesions. I would talk to him more about what are his specific concerns with systemic treatment and tell him about what we know about systemic treatment and how a lot of studies actually say more is better. And then if he agreed to try androgen deprivation therapy, we would talk about the forms of that which would range from surgical removal of the testicles, to a shot, to a pill.
Dr. Higano: Neal, do you have any other additional comments?
Dr. Shore: Yeah, I agree with Julie's thoughts. I think this has always been the conundrum. There are very few men who don't have some form of significant adverse effect from T suppression or what we euphemistically call T suppression, but it's really castration and it's very debilitating for most men. That said, there's unbelievable level I evidence, especially for this gentleman who now is 90, but he's very active. He's a very highly functioning 90 year old who, there's no doubt that the level I evidence would suggest now that he has recurrent, or not de novo, but recurrent or some would call primary progressive metastatic castration-sensitive prostate cancer. So certainly to have the conversation that combining T suppression as opposed to just simple monotherapy T suppression, but he could benefit from a combination with abiraterone, a combination with apalutamide, a combination with enzalutamide, and even arguably a combination now with docetaxel.
So it's tough. We always feel anxious about our elderly patients. Elderly if we arbitrarily defined it as 75 and over. Certainly as everyone's getting older, that number keeps getting higher and higher, and here's a 90-year-old former exercise enthusiast who's saying, "Hey, I'm worried about what I've heard." But yet clearly wants to keep living. So I would have a full-throated discussion with him and his family members that the level I evidence suggests that certainly combination therapy that will allow him to live longer. There is a trade-off to safety and side effects, but it'll arguably allow him to live longer.
Dr. Higano: Yeah. And he and his wife, I alluded to earlier are very intelligent and she does a lot of research on the internet of course. And one thing he said that helped me decide what to do was, he said, "Well, if I get an injection, it's going to take a long time to wear off." And I went, "Oh, well, have I got a deal for you." And so I explained to him about a new oral agent called relugolix, and, Neal, you were the PI on the HERO trial, maybe you might like to talk about the differences between relugolix, the oral antagonist, and leuprolide, the injectable agonist, and describe why I was able to suggest to this guy that, "Hey, if you stop this oral medication, the testosterone levels should return to normal ranges faster."
Dr. Shore: Yeah. Well, thank you. Yeah. So there's only one oral ADT that's now on the market that truly lowers testosterone quite effectively. We demonstrate that in the phase 3 HERO trial. We saw in two earlier phase 2 studies that this oral GnRH antagonist was extremely effective in achieving very rapid testosterone suppression by day 3, much like the parental deep subcutaneous administration of degarelix. The thing that we saw in our phase 2 studies and was clearly demonstrated in our phase 3 trial—we published this in The New England Journal—was that in a subset of the patients, about 180 patients, with a little over 1200 patients in study, and it was a 2:1 randomization—2:1 receiving relugolix, the oral once daily pill versus the administration of a parental LHRH—of 180 patients, a little over 50% on day 90 or the 3 months of the relugolix were back to their baseline testosterone or eugonadal as opposed to 3% in the parental LHRH administration.
And I think to your point, Tia, you could tell this gentleman that he has a -- the nice thing is with the oral GnRH daily pill, you can get a rapid T suppression, and at least half of the patients would have a rapid return to testosterone. So if he's so miserable, he could just stop taking it and expect a more likely rapid return. And historically with parental LHRH agonists, and even the antagonists, we can't always predict that rapid recovery. So for someone like him, who's so anxious of about it. This is a very nice alternative.
Dr. Higano: Yes. So I was able to convince him to try it, luckily. It's only been a couple months; his PSA is going down and he seems to be tolerating it okay. Although he certainly says he notices that he's on it. So he is not -- there are some patients we've all had who start ADT and they say they don't notice any difference, but I would say that's the exception rather than the rule.
From this case, I think there are some key clinical takeaways, and I'll mention a few and ask if anyone else has any others to add.
It's very clear that active older men, and even the younger men, may be very reluctant to start ADT due to the known side effects, especially fatigue and muscle weakness, and we have to really listen to our patients about what their priorities are, whether it's longevity or whether it's how they live their life today. Especially in these older men, I think it's very important.
The concept of metastasis directed therapy has been and is being studied extensively, especially in combination with metastasis-directed therapy by stereotactic body radiation, and it's not completely standard of care at this point in time, but I think in selected patients it can be very appropriate in terms of delaying the need for ADT, such as this patient chose to do. I think from a clinical standpoint though, if you're following such a patient in shortening in the time to PSA rise, and new metastatic disease can be an indication to start ADT rather than another round of metastasis directed therapy without any systemic therapy.
Finally, the rapid recovery of testosterone with relugolix can be an advantage in certain situations such as this case, or when ADT is planned for finite periods of time, such as with radiation therapy.
Do either of you have some additions?
Dr. Graff: Yeah, Tia. I just want to acknowledge that some of our patients don't follow regularly with their primary care provider, and I think that's a bad strategy. I always encourage my patients to follow with the primary care provider because of the modifiable cardiac risk factors.
Dr. Higano: Very good point. Neal, anything?
Dr. Shore: Yeah, I fully agree with Julie. Cardio-oncologic stewardship, really, really important these days for all cancer streams. People are living longer. These therapies, particularly ADT, have cardio-oncologic, cardiovascular implications. Just the importance of diet and exercise, getting the PCPs involved. We talk about multidisciplinary teams, and sometimes it's a challenge, isn't it? The physician shortages in some communities, it's hard to get a regular PCP, and sometimes they're stuck with the urologist or the medical oncologist filling that role. But I think as specialists we need to be cognizant of what Julie's saying and really help our patients make sure they're getting really complete care. It's an ongoing challenge in US healthcare, but I think we're making better strides in the last few years.
Dr. Higano: Great. Thank you both. So I think this brings us to the end of this case, and I hope you'll see the other segments for further discussion about the latest data in prostate cancer or visit ascopost.com.