Alicia Morgans: Hi, this is Alicia Morgans an Associate Professor of Medicine and oncologist at Northwestern University in Chicago and I am here today with Chuck Ryan who is the Division Head at the University of Minnesota, also a GU medical oncologist. Thanks so much for talking with me today.

Charles Ryan: Good morning, Alicia. Happy to be here.

Alicia Morgans: Great. So I think the two of us really have been experiencing a lot in terms of our clinical practice as it relates to COVID-19, the data that's come out, the stresses and the challenges of every day. And I think that we're also seeing a lot from our patients who are experiencing this dread that in some ways sort of reminds me of what they might feel when they first get their cancer diagnosis. That there's sort of this emergency that's happening, but you can't necessarily do anything that's going to fix the problem in the short run and it also hasn't hit catastrophe yet for many of our patients.

So it's this impending doom and this really big challenge about how do I act as quickly as possible when there's nothing I can necessarily do on a day to day basis. So I think we wanted to talk about that. We wanted to talk about what we're doing in our practices and understand the biology better for clinicians who are facing this. And I'd love to hear your take. Can you just go over a little bit of the biology of COVID-19 just very briefly, Chuck, so that people get an understanding of what we're dealing with from a biologic standpoint?

Charles Ryan: Well sure. So there's a lot of fear and a lot of worry in the medical community at large, not to mention the oncology community and cancer patients. It's important to remember that the rules and the recommendations that apply to all of us as general citizens also apply to us as physicians and cancer patients with regards to frequent hand washing and trying to limit exposure to others, social distancing, et cetera.

I think that the most important early sign that we're seeing of the impact of COVID-19 on oncology is the impact we are seeing on just the ability to practice medicine with regards to our usual way of doing business. We have converted a large proportion of our visits to phone visits. We have had our clinical trial operations completely shut down in order to limit the amount of resources that are going into the clinical operation so that we can have available space and resources for potential patients.

We're gearing for a two to three to maybe four-month period of time for this shutdown and a delay and a pause in our clinical trial development and we're responding to the guidelines that are emerging from ASCO and from the CDC and many other organizations about how to confront cancer patients and general patients with COVID-19. As a Division Director, as a leader of a large group of physicians here, I'm spending a fair amount of time coordinating how we are going to staff our cancer patients in the hospital, how we're going to run our clinics and we are also remembering that we are all trained as internists and so, we are reaching out and helping our hospitalist colleagues and potentially even our critical care colleagues in terms of helping to staff facilities. So there's a lot going on in terms of how we can respond clinically to this pandemic.

Alicia Morgans: Absolutely. And I think medical oncologists were trained as internists, some of us I think haven't practiced internal medicine for a long time, but there are many practitioners who touch the lives of patients with GU cancers who are not internists including urologists, radiation oncologists, and so, have just a very different background. I think just as a quick blurb, I'm sure that everyone has heard this, but remember these patients typically are going to present with the most common symptoms of fatigue and a dry cough, not usually a productive cough. These patients often will also have a fever which is usually going to be over 100, 102 in these adult patients. So these are the patients who we really want to make absolutely sure we are using personal protective equipment, isolating them when they do come into our clinics and that's what our teams are doing.

Certainly, we're wiping down every room and trying to make sure that we have a response team that can meet these patients when they come to clinic. But as you said, I think for any practice who's having patients coming back with routine visits or patients who are just coming back maybe for a symptom check or a well patient check in the longterm maintenance phase of their followup, we can hopefully convert some of those to telemedicine sort of visits or even push them back. Maybe have those visits in the latter part of the summer so that we can focus on those patients who are actively receiving treatment at this point. And as we think about how our care patterns are going to shift for those patients receiving active treatment, whether they're getting chemotherapy, whether they're getting AR directed therapies, whether they're getting immunotherapies, I think we're also having to make some different choices or at least consider the fact that some of the treatment choices we make may put our patients at higher risk for developing a COVID-19 infection that could ultimately be one that could be more harmful than in patients who don't have cancer.

There was some interesting data out of China that I just want us to sort of think through and talk through while we're recording that, granted, is a relatively low number of patients and also is a Chinese population... But this group identified prospectively over 1,590 patients who were diagnosed and had a test that was done and was positive for COVID-19 of those patients, 18 of those patients were cancer patients and they were able to report the outcomes on those cancer patients within that population. Are you able to review some of the findings from those 18 patients? Again, acknowledging that this is a very small number of the total number of patients who tested positive, 18 out of over 1,590 patients and this was also a population of cancer patients who are being treated in China.

Charles Ryan: Right. Well, I think it's really important to look at those data very, very cautiously before we make too many interpretations about our own practices here in the United States. The practice patterns for Chinese patients with cancer may be very different. Of course, there are many more than whatever it was, 1,600 patients diagnosed in China and so, we have to be very careful about making too many broad generalizations. They did report a relatively high mortality rate. I think that, as I'm thinking through this, a couple of points I would like to make is for our patients with prostate cancer, the vast majority of them are not on therapies that would lead to immunosuppression that would increase their risk because of their therapy. Now, many of our patients with prostate cancer are in an age range and may have a comorbid illness that may put them at greater risk should they become infected with COVID-19 but from that perspective, I don't think we should consider most prostate cancer patients to be immunosuppressed.

Obviously patients who are on chemotherapy who go through cycles of neutropenia are going to be at risk for bacterial infections generally, and if they were to experience a COVID-19 infection during neutropenia that could be very, very dangerous for them. And so, I would recommend that we consider being very cautious about the use of cytotoxic chemotherapy during this time. Having said that, there are people who need it and with the appropriate precautions it could be done, but I would leave that up to individual clinician's judgment.

I don't know if we want to talk about the other GU malignancies at this time, but I think that's an important message to get out with regards to prostate cancer patients and, in fact, I think that for many of them it is possible even that leaving their homes, coming to a clinic, waiting in a waiting room, being exposed to healthcare personnel perhaps even in the context of a hospital-based clinic could present more risks to them than skipping that appointment altogether and simply staying home. A delay in a couple of weeks of a Lupron® injection, a delay in a week or two of monitoring of renal function or hepatic function for a patient who's on abiraterone or enzalutamide is probably a minor delay and a minimal health risk compared to what we're seeing as a global public health risk for simply venturing out.

Alicia Morgans: Absolutely. So in those settings, though where we have patients with prostate cancer who are saying, for example, newly diagnosed metastatic hormone-sensitive disease, I'm having some really hard conversations with some of my patients about the treatment choice, whether they want to start with something like docetaxel chemotherapy in this setting in combination with their ADT or whether they'd prefer to use an AR directed therapy. And at this point, given the equivalent efficacy that we appear to have and the differences in terms of what these therapies cause in terms of the immunosuppression, for any patient who has not yet started therapy, we're actually pursuing AR directed therapy at this time. I don't think that it's necessarily the best idea when we do have a choice to recommend cytotoxic chemotherapy knowing that it causes immunosuppression in the middle of a pandemic. So at this point, we are choosing AR directed therapies.

When we think about other malignancies, we are not always in a situation where we have a choice, but certainly when we do have a choice, maybe immunotherapy over chemotherapy if it's the right clinical situation. But I think your message is loud and clear that we do not want to make choices for our patients that will put them in a poorer cancer control status just because we're afraid of something that might happen. So we do have to adequately and thoughtfully treat their cancer while we are also doing our best to protect them from the complications of the therapies that we could choose. And really for us also to acknowledge with every patient that we see, elderly patients with prostate cancer are at higher risk of having very catastrophic, in some cases, complication.

So it's important for us to counsel patients to use social distancing, to wash their hands and to be smart about this and sometimes those are hard things for people to hear but I think it is going to be important and it could be even more important for some of those particular patients as they're trying to go through their day-to-day. I think we should also acknowledge that ASCO as an organization has put out some guidance really stressing again that we should not compromise patient care and cancer control in situations where we don't have a choice, we do have to treat the cancer. For example, I have a number of patients with testicular cancer who are receiving active treatment with chemotherapy at this point. I would not make a choice to not give them chemotherapy for their testicular cancer just because I know that COVID-19 is out there.

We do need to treat the cancer and just acknowledge and be aware that we have to be extra cautious and even though those are young patients in most cases with testicular cancer, we have to acknowledge that they could get infected and be on heightened alert to put them in the hospital for management of complications if they do experience them. One of the things I thought was really interesting you mentioned earlier, just in terms of the biologic links, before we wrap this up, there are some interesting things for us to think about specifically as they relate to prostate cancer and the COVID virus binding. Can you tell me a little bit about TMPRSS2 and what you've learned about COVID-19 in that setting?

Charles Ryan: Sure. You raise an interesting question about the biology of COVID-19 and it's been kind of fascinating. I've spent a lot of time in the last few days reading what's coming across. First of all, I want to say that it's quite fascinating that there are already peer-reviewed publications coming out on this particular epidemic even in its early stages. The New England Journal of Medicine just yesterday, March 18th, sent out an edition that was almost entirely related to COVID. That's quite interesting. There have been case reports, there have been a series published from the China Experience and other countries experience already coming out in the literature. There's a couple of interesting links to the biology of what we do, which I think is maybe at this point trivial maybe at this point going to lead to something. The first is that I noticed this is not really related to prostate cancer, but I noticed that there are now cases of anti-IL-6 antibodies being given to patients with ARDS.

The interesting thing is that there are cases of anti-IL-6 antibodies being given to patients with ARDS from COVID-19, which is a way to treat the most advanced stages of the infection and there have been some clinical responses from that and that's an interesting thing that we'll want to follow because those are drugs that are available. I believe Genentech makes that that particular agent. The second is the finding that COVID-19 when it binds to alveolar epithelial cells in the lung, binds to what I think is essentially a dimer between ACE2 or angiotensin-converting enzyme 2 and TMPRSS2 and those of us who study the biology of prostate cancer know TMPRSS2 quite well because of the TMPRSS2-ERG translocation gene and protein that we think is involved in increasing the risk of recurrence after therapy for prostate cancer.

What is intriguing to me is that TMPRSS2 we think is an androgen driven gene. It has an antigen response element in its promoter region and so, one of the questions I'm going to be following is whether or not there's a difference in outcome between men and women with COVID-19. It appears there may be some differences but it's still early days. But the other angle on that is whether or not ADT treated patients may actually have a better prognosis or decreased risk of COVID-19 infection. This is pure conjecture at this point but is an interesting link to what we think about every day.

And then along those lines, could androgen receptor blockade actually impair COVID-19 binding? Again, pure conjecture at this point. That would be a hypothesis maybe worth testing. It is interesting, however, that the ACE2 link is being explored therapeutically. So ACE inhibitors and at our center angiotensin receptor blockers are being studied in clinical trials in patients with COVID-19 infection. So this is one of these areas where we might see the development of off the shelf products helping to mitigate some of these infection risks. I would say that to anybody listening that it's important that we adhere to the principles of disciplined scientific rigor because we don't know this, this is pure conjecture and hypothesis at this point. And yet as a prostate cancer researcher, I read through what's going on and these little highlights pop up as sort of interesting.

Alicia Morgans: Absolutely. So at this point taking precautions in terms of staff who are caring for all of our GU oncology patients. Taking precautions for our patients, recommending that they wash their hands, stay away from others with social distancing and consider, if they're able, putting off visits to healthcare institutions if they are well and are able to stay home and reschedule a routine followup visit with their oncologist or their urologist, perhaps that is the best way to go and to be in touch with their physicians if they feel like they have questions about their cancer care is going to be really important. Ensuring that we acknowledge when patients don't have the opportunity to defer their care. When we see patients who absolutely need to be treated now for things like testicular cancer or situations where we have prostate cancer patients who don't have a choice about delaying things like chemotherapy.

We do need to have those hard conversations with patients, with our staff, with patients' families, and make sure that patients get the treatment that they need. But when we do have the choice, doing whatever we can to really reduce our contribution to patients' immunosuppression or inability to fight COVID-19 should they get it is going to be important. So best of luck to all out there. And thank you, Chuck, for taking the time to share your expertise and what you're doing at your institution and how we can continue to move forward as a group of oncologists and people who care for these patients to do the best that we can each day. Thank you.

Charles Ryan: Thank you.