Alicia Morgans: I think it's a great question and one that's been answered thankfully repeatedly in prospective randomized phase-three trials that led to the approval of androgen receptor pathway inhibitors in combination with ADT in the metastatic hormone-sensitive space, if we want to focus there. I think what we've seen repeatedly is that when we intensify therapy as compared to ADT alone, we're certainly prolonging time to progression. We're prolonging survival, which is critical. But we are also in most cases at least maintaining if not even improving quality of life. And the only reason to really withhold something from someone in this setting I think is if we aren't doing both of those things, or if we're really just improving the length of life but not helping people maintain their quality of life or improve it, what is the point? Especially if we're talking about some very maybe older people with comorbid illnesses that are going to shorten their life expectancy anyway. But I do think it's worth the conversation.
I guess the only other thing I would mention is that financial toxicity could be a reason that we wouldn't do this. In our older adult patients, this is always going to be potentially more impactful as they are often on a fixed income. But usually I think we can get by that in our clinics with our supportive teams and with the support from different companies that often offer free drug in certain settings.
So really I don't think that there's a clear reason to necessarily withhold if we have the opportunity to intensify and the patient's willing.
Zachary Klaassen: Yeah, it's a great background. I think when we look at these patients, we don't want to do something to disrupt their quality of life because they probably will die of something else. But at the same time, there's some patients that can benefit, as you mentioned, improving quality of life and avoiding some of these things like skeletal fractures and the things that we dread with prostate cancer. You've done a lot of work in sort of figuring out who's the patient that may do better or may not do better, just from a cognitive standpoint, from a functional standpoint. Just talk about some of the tools you use in these older and more comorbid patients.
Alicia Morgans: Sure. I think we recognize that chronologic age or the number on the patient's chart is very different than biologic age. And so we can use standardized methods to try to understand this. The International Society on Aging has really suggested that we think about using things like a mini COG, which is a very brief assessment of three questions to try to get a sense of whether someone has their decision-making capacity, and then think about defining them in terms of their frailty status using the G8, which is eight questions, thinking about things like weight loss, polypharmacy, the patient's perceived health status, and a few other questions, eight questions as you might expect. And importantly, I think the G8 is actually associated with mortality. So if one has a score under 14, I believe, then they have a higher risk of mortality aside from their cancer and from the treatments that we give.
Understanding where they fit on that spectrum can be really helpful. But for many of us, we don't necessarily have time to do all of these things, even though they're brief. So one of the things that's pretty easy is watching a patient walk into the room, sit down or get up from a chair, and walk out of the room; looking at the supports they have, looking at the tools they use to try to get up and get around and reduce risk of fall; talking to family members about, are you concerned about anything? Is this person forgetting things more than normal? What bothers you or what worries you? And often family members will bring these things up and then you can dig in a little bit more. Because it is really difficult in a brief visit to do these standardized assessments, though some practices do routinely. Even just getting hints from family or loved ones about what they're worried about in terms of the person's function can give us a line of questioning that we can pursue pretty quickly and understand if there's a problem.
Zachary Klaassen: I'm glad you brought up the family and the people that are bringing the patient to the clinic, because they'll often give you insight if you ask them or even if they don't ask them. And I think that's important to be attuned to that as well. We have so many options with doublet and triplet therapy. When you're having these discussions with the patient and their family or caregivers, which direction are you taking those doublet versus triplet discussions?
Alicia Morgans: These can be pretty complicated because it's not unusual for someone older or younger to come in and say, "I really want to stay exactly as I am. Don't give me side effects." And the other side of the coin, "I want to do everything possible, throw the kitchen sink, let's do this."
Zachary Klaassen: And there might be younger old people saying both of those.
Alicia Morgans: Exactly. It could be either one. So I really try to bring it back to the disease. How aggressive is this disease? Is it de novo metastatic? Is it high volume? Is it low volume? And understand from a cancer perspective what my goal is in terms of treatment. Certainly if there's a gray area, we can have conversations around that and we do have conversations around that.
But understanding, to start, what I would ideally like to do from a cancer perspective is really important just to anchor what I think should happen for this patient. And then we layer in patient comorbidities and concerns around self-care or supportive family members or others in the patient's life just to think about, is this patient actually going to be eligible as an individual for something like chemotherapy? Do they have the performance status? Do they have the functional status and the support that will get them there?
If all of these things look like triplet is preferred, that's when you have the shared decision with the patient about what are your goals? What are you willing to do? What are you not willing to do? And understanding you can get chemotherapy now or later. When do you think it's right based on the fact that it'd be six cycles and done now, or maybe we can use it in the future as one of the options that we have down the line. If it's going to be more cycles, it may be harder, you will be older. So I think kind of rounding that out and understanding where the patient wants to be is really important.
But we're fortunate too that when we're trying to make these decisions around doublet and triplet, we do have studies that are ongoing trying to understand the specific contribution of chemotherapy. So if we have access to those trials, we can also encourage patients to participate in trials and get the support of the clinical trial team as well to try to answer some of the questions from a biologic perspective. Do we need the chemotherapy?
I would say I don't withhold chemotherapy because of someone's age. I, again, really focus on the disease related characteristics and the patient's goals and try to make things work to the best of my ability for what the patient also wishes to do.
Zachary Klaassen: It's a great answer to a complicated answer. There's a lot going on, and it's an individual discussion with the patient I think is important. When you start these, say, older or more comorbid patients on whether it's double or triplet, are you following them any closer? Are you altering your follow-up schedule for these patients at all?
Alicia Morgans: We follow, at least as we're starting treatment, every month for the first couple of months for many patients as we start ADT and then next we start the ARPI, and we always do a month later sort of safety and tolerance check just to mitigate any side effects and try to make sure that the patient's still going in that direction. If we layer in chemotherapy, then it might be at month three or four, and then that's going to be an every three week follow up. So that's pretty close. And that's actually really important. I think sometimes if we're kind of concerned about a patient and their ability to be okay at home, we will do some phone check-ins by the nursing team in between.
But if they're just on ADT and ARPI, I don't think we necessarily follow them more closely for their age. We definitely will scan them maybe a little more closely if the PSA isn't responding adequately or if there's anything about them that seems just off, again, from a general medical perspective, but it's not their age that would necessarily drive that. It's more disease related factors or comorbidities or maybe social supports.
Zachary Klaassen: What about the patients where they may have some DDIs potentially? Are you choosing an agent differently? Are you following a little differently based off of that?
Alicia Morgans: Well, we definitely have to think about that. We're fortunate, at least in my clinic, to have a pharmacist who can help if I feel like I'm stuck and I want to use this agent or that agent, but the drug interactions won't allow me to do that. So we try to work that out on the front end. Sometimes the combination that we use does require closer monitoring. And then we decide whether that's going to be maybe with the team that's following the INR or with the team that's monitoring the statin. We try to engage those teams and communicate very closely. Because it's not necessarily the cancer drug that needs to be altered. It may be monitoring that's more related to the other agent, and so we try to make sure that that's tied in.
Zachary Klaassen: Lots of collaboration in the disease space.
Alicia Morgans: Yes. I think the busy oncologist, urologist, urologic oncologist doesn't necessarily need to make those calls. And in fact, I almost never make those calls. Those are made by the team. And that's why we have teams, so the nurses and the pharmacists and the nurses, and the pharmacists on the teams for the PCPs and the cardiologists or the INR team. So this is a group effort and I think any individual physician should not feel like they have to take it all on themselves, but to work with their teams to build out the supports to have that communication.
Zachary Klaassen: Such a great discussion, Alicia. Thank you so much for joining us and for your time on UroToday.
Alicia Morgans: Thank you so much for your time, Zach.