Just to talk more about David, you are so multifaceted. You are a associate professor of education and health at the Wolverhampton University in UK. We really appreciate you taking the time. We really enjoyed your talk at the APCCC meeting, and we will love to glean more from you on how you look at radiographic progression-free survival as a patient.
David Matheson: Thank you very much, Neeraj. It's a great pleasure to be here with you. So how relevant is radiographic progression-free survival from a patient's point of view? There's my quick disclosures. What you have is a lot of questions. Patients having the scans and so on, a lot of questions have been asked, and then you've got to make a decision.
So, how do you decide? And this is one of the big problems with this. If you're relying only on scans, then it feels abstract. But the questions you have to answer are not only clinical, they're also social and personal. The patient has a context. There's beliefs and preferences, there's social norms, and so on. And any treatment decision has to fit into that context. So what the patient has to make is not just an informed choice with the given information, but an authentic choice. To see, how does this all fit into me as I see myself, and how I see the world around me, my social context, et cetera, see me.
And there's also the need to acknowledge uncertainty, which actually, when you're in this situation, uncertainty really brims over the top of your cup. So what am I to think if my PSA is rising, but there's no change in my disease according to the scans? Should I trust the scans and those that are interpreting them? Or should I trust the biochemistry more than the scans? And having been in this position, it really is a very awkward place to be.
And then the question is, how important is it for the patient to delay time to progression on imaging? As a patient, I can't actually see PSA. It's pretty much an abstract concept. But I can see images on a scan. If you show me, you point out, "Here's a tumor, a tumor there," whatever, you can give me the size of tumors, you can talk about the rate of growth, et cetera. You can explain to me what I'm looking at.
And if you do that, you're empowering me much more, rather than this difficult-to-grasp concept, which is PSA. So question, is delay as important as prolonging survival or less important? Well, I have to think, what is the delay actually for? Who is served by the delay? Is it serving the disease? Is it serving the patient? Is it serving quality of life as measured by the patient? Because really, that's the only one whose measure of quality of life actually counts.
And one suggests the thing that's important is maximizing wellness in the circumstances. Wellness is a concept that's very often overlooked. Medics, naturally enough, deal with illness. Person comes to them because they are ill. They have an ailment. Patient comes because their wellness is disrupted. They want to return as close to that wellness as possible, to re-achieve wellness, and to do so for as long as possible.
And that's not possible if the treatment makes one more ill than the malady did. And it's something that's really got to be taken into account. You think, "Am I going to start treatment which will make me quite ill?" Because a lot of the treatments do. Between flashes, emotional fragility, all of these things, whatever you've got, you can be feeling much less well than you did before you started a treatment. Has to be explained to me the worthwhileness of this. Thank you very much for your attention.
Neeraj Agarwal: So David, that was a very nice talk. And you really put the patient perspectives into it, such as radiographic progression-free survival may be more meaningful to you than PSA, because you can actually see the images. On the other hand, if I perceived it correctly, radiographic progression-free survival is only meaningful to you if your quality of life is not disrupted. Am I correct?
David Matheson: Absolutely. Yeah. There's quality of life, this is as measured from the patient perspective, not done by using things like the EORTC questionnaires, which are really very much done from a clinician perspective. They're examining, I think, to a large extent, what clinicians have thought they would feel in particular settings. I've mentioned APCCC before, the fact of the QLQ-PR25 that asks about nocturia. And it says, "How often in the last month have you had to go to the toilet during the night?" Never? That's fair enough. Sometimes, occasionally, and then often. What's this? It's a terrible question. What it doesn't ask is how much does it bother you? And how much does it bother you, that's a measure of the quality of life. Different people are bothered by different things. Some people will cope with flushes, doesn't bother them at all. You save on your heating bill while you're actually having a flush.
Others, their lives are really devastated by the same kind of thing. So it's got to be the patient who decides in this, the patient who's saying, imagining, "If I start treatment, what price am I going to pay for?" I'm not talking ... I mean, depending on what system you're in, the financial price might be significant as well. I live in the UK, so there's no financial cost at all. But that could be a significant factor if you're in the US. But there's also the physical, the emotional cost, and so on. All of these drugs come with potentially very strong emotional challenges to you, especially if you be developing it or suffering emotional fragility. Society looks very poorly on, certainly UK society, and I think US society is pretty similar. A woman bursting into tears doesn't get very much sympathy. A man bursting into tears can be the object of really disparagement and even hatred. And if you're going about feeling that any moment you might do that because of the medication that you're on, that puts an enormous strain on you.
On the other hand, you might think, well, if I burst into tear, and if somebody else reacts to it, that's their problem. Different people react differently, and it's to actually know from the patient and to check at regular intervals how it is for them. Have you had this? And don't use questions like, "How's it been?" Patient, "It's fine." It's the end of the conversation.
Say, "Have you had emotional fragility? How's it been? How do you feel about it?" All of these things. But you see, by talking about it, you get what's actually being lived by patients. So if they do have radiographic progression-free survival and they're thinking, "Well, the disease is looking pretty stable. Should I just leave it there while it's stable?" My PSA, for example, went up to 15, it sat there for about a year. The tumors which I have didn't change at all, and then it began to bump up a little bit. I don't think the tumors changed at all. So radiographically, I was progression-free, but biochemically, I had some progression, hence going back onto a systemic therapy.
Neeraj Agarwal: Yeah. I appreciate your perspectives. Now, looking at the overall survival, as we know, this endpoint of overall survival takes much longer, especially when you are talking about metastatic hormone-sensitive prostate cancer setting, or the new terminology is androgen pathway modulation-sensitive metastatic prostate cancer. It takes much longer, and we wait for overall survival to be available for all these agents. It will likely result in delaying of approval of many of those drugs by years, maybe.
David Matheson: By decades, even.
Neeraj Agarwal: And so what is your perspective on this? What do you think about overall survival versus radiographic progression-free survival? And are you happy with the fact that many drugs are now being approved based on radiographic progression-free survival?
David Matheson: I am very happy with that to occur. And as you say, otherwise we'd be waiting for a very, very long time. It took a long time to move from only having estrogen injections as the only therapy available, with all the side effects that brought, into the various GnRH agonists, whatever, and then the enzalutamide, the -amides, the -aterides, and -aterones like abiraterone and so on. Those took a long time to come along.
And it's through work and things like STAMPEDE, which I'm a member of the trial management group, that eventually we start to get approvals getting granted and so on. But this is way before most people have actually ... Some have died off in the course of the abiraterone arm in STAMPEDE, sadly. But most haven't. Most are still there. We can't wait. We've got to actually take action. And if it's explained to people how far these things have got, then you're starting to get into getting an informed choice that can then lead to an authentic choice.
So if I choose to take these things, I know the extent to which they've been tested. I know that, to some extent, I'm putting my faith in things. We did that with the COVID vaccines, and to a large extent, stopped the pandemic in the bud. I mean, there just wasn't the time to do the level of testing which normally would have been required. Therefore, it went ahead. There were obviously some tests, phase-one, I think it was straight from phase-one to people being injected with things. Check that they're as safe as you can make them in the circumstances. If the risks are explained, again, there's a sense of empowerment, there's a sense of patient choice. And with patient empowerment and patient choice comes a diminution in the chances of treatment regret as well.
Neeraj Agarwal: Any final points on radiographic progression-free survival as an endpoint, as a patient?
David Matheson: As an end point, well, when does it end? If I start to get to progression, and my radiographic progression-free survival comes to an end, well, is that the time to change protocols or whatever? Should I be waiting longer? Should I be using this instead of or as well as biochemical progression? Which one really is the more important? And that's something which, again, explaining the risks and benefits to me, I'll give you an informed response.
Neeraj Agarwal: Thank you so much, David. We really appreciate you taking the time.
David Matheson: It's been a pleasure.
Neeraj Agarwal: Just to summarize David Matheson, or I would say, David, first of all, you're not only a associate professor, you are also a patient, and you are taking the time to educate us about patient's perspective. So I would like to especially thank you on behalf of all of us as the community, on behalf of PCF and UroToday for being here.
Neeraj Agarwal: And what we finally got from you today is radiographic progression-free survival is a relevant endpoint, because it expedites the read on several trials, which otherwise would be delayed if they are completely relying on overall survival endpoint for drug approval, delaying the access to our patients to those drugs for a very long time. But you also like to have quality of life as reported by the patient to be an integral part of the endpoints. And of course, PSA progression remains an endpoint which is very relevant to the patients. So thank you very much.
David Matheson: Been a pleasure. Thank you very much, Neeraj.