Phillip Koo: Welcome to APCCC 2019. We're very fortunate to have with us today, and I'll use the introduction that we used for his presentation, a rock star who in his side job is a Professor of Radiation Oncology at Queens University, Belfast, and a Consultant Oncologist at the Northern Ireland Cancer Center in Belfast as well.

He's very well known to us at UroToday and is someone who really is a pioneer with regards to radiation and systemic therapies in prostate cancer. So, thank you very much for joining us.

Joe O'Sullivan: Thanks, Phil. Good to see you.

Phillip Koo: So you know, the cancer issue in the geriatric population has been described as a ticking time bomb. We know it's coming and it presents a lot of unique challenges for the community.

Joe O'Sullivan: Yes.

Phillip Koo: Can you talk a little bit about that assessment piece upfront?

Joe O'Sullivan: Yeah. Well as you know, most cancers are diseases of elderly and that's certainly true for prostate cancer. The median age of diagnosis in the US is 67 and the median age of death is well over 80, so most patients who die from prostate cancer are over 80 years of age when they die. That means that the treatments, especially for advanced prostate cancer, are most likely to be in elderly patients. And this presents issues because as we get older, inevitably we develop more comorbidities. We may be less able to tolerate different drugs, and also priorities change in life.

So when we're talking about an evidence base for whatever therapy we're proposing for a patient, I think it's very important to bear in mind that this population that we treat our elderly and are prone to other problems. So we need to really bear that in mind when treating these patients and making sure that we don't push them into a state where they become frail or their quality of life deteriorates. I think it's very important.

Phillip Koo: So in your opinion, where are the biggest opportunities in the short term for us to make an impact in this geriatric population?

Joe O'Sullivan: I think there's two parts. I think firstly it's just assessing the patients. So when a patient comes to our clinic for treatment, I think particularly for patients over 75, but this may be also applicable to some younger patients if they have comorbidities. But for patients over 75 as well as assessing the disease and their scans and their histology et cetera, we should also do a sort of basic geriatric assessment, and that's looking out for things that are more common as patients get older. For example, difficulty eating, maintaining their weight, the fact that they may be on multiple other drug therapies which may interact with the therapy being proposed.

There's a very nice tool actually called the G8, and this tool is a very, very nice, simple way to assess an elderly patient. It's an eight-part tool, and it looks at diet, polypharmacy, have they had falls, and are they over 75 years of age? If they score low on this then they probably should go for a full geriatric assessment, and if they don't, I think if you just push on and treat patients who have a low score, you are running into the danger that the treatment, the chemotherapy or the hormonal therapy may actually make the patient much worse.

So I think a good assessment, and then having a low bar for referring patients on for more specialized geriatric assessment.

Phillip Koo: So transitioning to the therapies, I've noticed in my practice as a nuclear radiologist that we often get more referrals for patients for a drug such as radium, where patients are refusing a chemotherapy due to their age and they don't want to deal with the side effects. What have you seen on your end and where those opportunities for therapy?

Joe O'Sullivan: Yeah, so I think particularly when patients are assessed and they're found to be in the more vulnerable or more frail categories, sometimes there's no treatments that are suitable for them, however there are a number of cancer therapies that in general are better tolerated. For example, in the hormone-sensitive metastatic space, most patients can tolerate a hormonal agent, most patients can tolerate local radiotherapy, but a significant proportion of especially of the 75 or 80 plus patients are not capable to tolerate chemotherapy or indeed chemotherapy may push them across the edge.

I think therapies like radium especially is one which I find very tolerable in an older population. From the safety profile point of view it really is not so hard on their bone marrow, and other physical functioning seems to be preserved well.

However, some of the new hormonal agents, while in general are well tolerated, some can increase the risk of frailty themselves, actually even in younger patients, but especially in older men. I'm thinking particularly about drugs like enzalutamide which have been shown to increase falls, and I think that's a particularly important issue for elderly patients. If an elderly patient falls and especially if they break a limb, it's a huge impact on their survival, irrespective of the cancer.

Phillip Koo: Sure. So that sort of transitions into the idea of bone health.

Joe O'Sullivan: Yes.

Phillip Koo: How do you think we're doing with regards to bone health, and what should we be doing tomorrow?

Joe O'Sullivan: I don't think we're doing too well on it yet, but I think our eyes have been opened about it from a number of trials, in particular trial ERA 223, which was a trial using abiraterone plus or minus Radium-223, and this really exposed a fracture risk which was in part due to the combination of abiraterone and radium. But really it has opened our eyes to the fact that almost all the agents that we use, ADT, abi, enza, radium, et cetera, bring with them a fracture risk.

And along with that, the elderly population as they get older are also increased risk of fracture, because while there's been a very, very large amount of work done on female osteoporosis, much less so on the male side. Female because of menopause and things like that, but in men, it's just as big an issue, and especially when we're talking about the age category above 75 and especially men who maybe are not as active physically.

These patients really need their bones assessed, so in my clinic we do a FRAX score to determine what's the risk of fracture. Most patients over 75, especially on ADT, do have a high FRAX score, so they do merit further assessment. So we will do a DEXA scan looking at bone mineral density, but actually for most patients now, elderly men, if I'm starting ADT, I also start a bisphosphonate, usually an oral alendronate. And I think I'm also much more conscious of it in men with castration-resistant disease as well, because as well as bone mets causing a fracture risk, the osteoporosis that underlies that as well means that their whole bone structure is just not as good as it should be.

Phillip Koo: Sure. So final question is, are there any clinical trials looking at the geriatric population specifically in prostate cancer?

Joe O'Sullivan: There really are not, and I think but what's really encouraging now is that most of the large clinical trials would permit patients, and in fact reviewing the literature for my presentation, many trials are patients well over 90. However, when you look at the criteria for entry, so they have to be performance status one, all their liver function, kidney function, et cetera, that actually excludes quite a lot of elderly men.

So one of the theoretically and you know, STAMPEDE, LATITUDE, et cetera, have patients in their 90s, the vast majority of patients are younger than our typical clinical population. So I think there's been a renewed effort, especially from groups like SIOG trying to encourage clinical trialists to include elderly patients, and you have to be a little bit more flexible with the entry criteria. But then, of course, the results of your trials are more applicable to real life, which is very important I think.

Phillip Koo: That's great. Thank you very much for your work in this space, and we look forward to hearing more about the onco-geriatric population.

Joe O'Sullivan: Thanks, Phil.

Phillip Koo: Great.

Joe O'Sullivan: Cool.

Phillip Koo: Thank you.

Joe O'Sullivan: Yeah. Great interview. Thank you.