Alicia Morgans: Hi, this is Alicia Morgans, GU medical oncologist and Associate Professor of Medicine at Northwestern University in Chicago. I am so excited to have here with me today, Dr. Nick James, who is a Professor of Prostate and Bladder Cancer Research at the Institute of Cancer Medicine and the Royal Marsden in London, England. Thank you so much for being here today.

Nick James: Pleasure.

Alicia Morgans: So Dr. James, we wanted to talk with you a little bit today about the COVID-19 pandemic and how it's affected you, as well as the ICR guidelines that you and your group have put forth to really improve or, at least, standardize the care for patients with cancer. So, how have things been for you in London with the COVID-19 pandemic?

Nick James: They've been very strange, I think it's fair to say. So, London ended up getting hit by it first but, obviously, we had a bit of time to gear up because we could see what had happened in Italy, and Spain and so on, who were a bit ahead of us.

So, the first thing that happened was that a lot of elective surgery, cancer surgery, non-cancer surgery, hip replacements, all this stuff was canceled and hospitals were kind of cleared in the expectation that we were going to get swamped with a lot of COVID cases. In the event, we didn't get swamped. The ICUs never actually completely filled up, but there were certainly an awful lot of COVIDs coming in. And, as you sadly know, we're topping the European league of deaths from COVID.

But, within London, what happened was that very early on in the process, there was a pan-London group set up to try and figure out the best way through all of this. So, within the cancer context, we prioritized what we really had to do. Lung cancer surgery, stuff like this where you really die quickly if you don't get treated versus stuff you didn't need to do, so prostatectomies being the most obvious thing here. So, it was decided that, as a holding exercise, people who were waiting for prostatectomies were put on the hormone therapy short term.

And, in parallel to that, plans were put in place to separate COVID sites from non-COVID sites. So, something like the Marsden was an easy pick for a non-COVID site, obviously, as we only do cancer. But one of the other things that was a feature of the UK was we were disastrously slow in getting large scale testing for COVID up and running. So, we couldn't do diagnostics to figure out who had it and who didn't. So you couldn't pre-screen people, for example, we just didn't have the capacity.

So early on, pretty much everything stopped in prostate cancer. People were not being biopsied. If they'd already been biopsied, not treated, they were just put on bicalutamide 150 mix as a holding exercise while we figured out what to do next. In bladder cancer, things largely stopped as well. So we were left with people who were diagnosed, but people upstream with symptoms were just parked in the GPs, really.

There was a big debate early on as to whether we could carry on doing bladder cancer surgeries safely because obviously these are mostly men who seem to be two to one higher likely to die of COVID than women. They are mostly elderly, often smokers, often with co-morbidities. These are people obviously at very high risk of picking up COVID and then dying from it.

And so we had quite a big debate across London and nationally. And actually I published a paper with Alison Birtle and others on the UK recommendations on this. Because we felt, and still feel, that chemoradiotherapy with drugs like [inaudible 00:03:40] mitomycin were safe. And as it's turned out there hasn't been an issue delivering that treatment. And anecdotally across the UK, my colleagues have reported a switch from cystectomy towards bladder preservation with chemo RT. And that's against a background were already over half of UK cases are managed with primary chemo RT, not with surgery. So we've already got a high base and it went even higher.

The second thing in the context of bladder cancer and neoadjuvant chemo, and we've gone the opposite way with that. We took the view that was probably risky, didn't give you a massive gain versus the risk for most of the patients. So we've largely backpedaled on that. And then down the line for systemic therapy, there's been a prioritization of immuno-oncology agents over chemo, where you had that option.

So that kind of all makes sense. And subsequently, actually, we've done audits showing that our bladder cancer outcomes with surgery are fine. We've managed to separate the COVID cases from the general run of the population. Patients are told to isolate for two weeks before the cystectomy and we haven't had any COVID deaths across London having cystectomies, as far as I'm aware at the last audit, which was last week.

Alicia Morgans: Well, that is wonderful. And I really appreciate the way that your team, and actually your country, the NHS, really came together to put forth several different statements to really help guide how people are going to be managed in this setting. I was curious though, sometimes there are drugs that we certainly have access to in the United States that are more difficult to get through the NHS. Was this an issue at all?

Nick James: Oh, absolutely. So prostate cancer, the thing that came up was we discouraged GPs from sending men in just with raised PSAs for example. And in fact, actually, now we're finding that we told the GPs they can send those men in again and people are not wanting to come. So actually, one of the things I want to do when I'm done with this is record a video around how we're making COVID safe environments for patients to come into.

So the only patients that GPs could refer in were men with suspected metastatic disease. We obviously had men in the system who had already been diagnosed with metastatic disease who were being teed up with docetaxel. Within the UK at the moment, abiraterone is still going through NICE three years on, so we can't access abiraterone. Enzalutamide went through NICE, which is our clinical prioritization, value for money thing, the week before last. I was one of the experts giving evidence on that, we don't know the outcome yet. Apalutamide is yet to go through NICE.

So although we've got three hormone therapy agents, which give you a big improvement in survival, a big reduction in morbidity, until the COVID epidemic we weren't able to access them at all. We only had docetaxel or ADT alone. And so a group of us, led by myself and Julia Murray, drafted a letter to NHS England saying this makes zero sense. We don't want to be giving men chemo in these high-risk times when we can literally mail them pills that will work at least as well, if not better and improve their quality of life and keep them away from the hospital for years, compared with bringing them in every three weeks for chemo.

And that rattled around inside the system, as these things do, for a while, but has resulted in NICE approving enzalutamide, or abiraterone if you can't tolerate enzalutamide for men with newly diagnosed metastatic hormone-sensitive prostate cancer. Which is always obviously really good news.

The Celtic bits of the health service had slightly different policies anyway. So Scotland's had already approved abiraterone and Wales, actually very unusually is normally the most stingy, approved apalutamide, enzalutamide and abiraterone for use all the way down into the node-positive group. Which I think was probably the best decision actually.

So we've got slightly patchy access across the UK at the beginning, but actually now very good access across the UK for these therapies. And obviously it makes sense, you can do everything by remote control. We're doing all our clinics remotely now, as I suspect you are. Virtually nobody's coming in face to face or they're coming in having a blood test and going home.

So yeah, it makes sense on every level. And now we're hoping that it sticks post COVID because the worry is they'll reverse it again as soon as they think it's safe, although it's not looking safe for a while yet.

Alicia Morgans: Well, that's a big win. So I'm very glad that you were able to get that through for your patients. The other decision-making point that might be tricky. As I was looking through the guidelines, it looks like for patients with bladder cancer, immunotherapies, and you've mentioned this, have been really prioritized over chemotherapies.

In the United States, at least based on some of the early evidence from the metastatic trials for patients who are chemo eligible prior to the pandemic, we had a recommendation. If you're cisplatin eligible to really proceed with cisplatin in the metastatic setting over the immunotherapies. Is this something that you have changed given the pandemic, which is completely reasonable? I'm just curious.

Nick James: Yes, it is. So at the moment, we're told to prioritize. Obviously the data's the same for us. The current thing is we can either prioritize or switch to an IO agent for patients who are suitable for it. And in the first line that's irrespective of PD1 [inaudible 00:09:24]. And obviously particularly the patients with good expresses of PD1, PD-L1, probably they would do better with the chemo but narrowly. But these are really high-risk patients.

Alicia Morgans: It's incredibly impressive what you and the others in the country have been able to do on a national level to really improve the care of your patients and keep them safe. It's a wonderful win. And I wonder, and you mentioned this as well, are you expecting that these guidelines may be in place for a longer period of time? Or as we don't know when this pandemic is going to end, perhaps you expect that they're going to expire essentially when the pandemic does, if it does?

Nick James: Obviously we don't know what's going to happen down the line. I personally think it's safe to assume that we're stuck with dealing with COVID or things like it forever. I can't see how we can ever eliminate these things. Mostly this has been a disaster obviously. Economically, politically, everything has been horrible about it. And we're looking at a huge recession here, I suspect it's not going to be very different your side of the Atlantic.

But there've been some pluses. One is that it's shifted the NHS lock stock and barrel to telemedicine pretty much overnight. And mostly that's a good thing. Some things, yeah, I think are better face-to-face, but an awful lot of stuff can be done without dragging somebody in and making them wait for three hours to see you in 10 minutes. So that's going to be positive.

And it's also forced a reconfiguration of services. So it's made us separate elective stuff from acute stuff to a far greater extent than happened before. And I think there's a lot of economies of scale and organization that you get from doing that. So I think a lot of these reorganizations will stick post-COVID and will be to the benefit of patients.

It's also made people reassess the risk-benefit of bladder preservation versus surgery, for example, in bladder cancer. And I think a lot of those things will, even though we've established the surgeons can operate safely, they're having to do it in full PPE. Is that an acronym used in America, PPE, personal protective equipment? So it takes them an extra 40 minutes each end of the operation, putting this stuff on and taking it off, which makes surgery less fun and appealing.

So I think it's going to make a lot of stuff be reappraised more longterm. Obviously some things that have funding implications, like funding upfront hormone therapy, additional hormone therapy for men with prostate cancer comes with a price. But I think there'll be so much less enthusiasm in giving docetaxel, that I think I'm pretty hopeful that will stick. I think it should.

Alicia Morgans: Great. Again, congratulations on the changes that you and others have been able to make. They really are transformative and are an exceptional way to ensure the health of your patients. And I sincerely look forward to hearing from you again and keep up the good work.

Nick James: Thank you very much.