Alicia Morgans: Hi, this is Alicia Morgans, Associate Professor of Medicine and GU medical oncologist at Northwestern University. I am so pleased to have here with me today a good friend and colleague, Dr. Joshua Meeks, an Assistant Professor of Urology also at Northwestern, as well as an Assistant Professor of Biochemistry and Molecular Genetics. Josh and I work together a lot clinically for patients with bladder cancer. Of course, he has a lab where he is always trying to innovate and to find next steps for patients with bladder cancer. Josh, thank you so much for taking the time today to talk with me about COVID-19 and its impact on your practice for patients with muscle-invasive and non-muscle invasive bladder cancer.

Joshua Meeks: Thanks, Alicia. Good to talk this morning.

Alicia Morgans: Of course, so let's start with patients with non-muscle invasive disease, and I'd love to just hear how has your decision making changed? How has your practice been affected by what we're experiencing right now with the COVID-19 pandemic?

Joshua Meeks: Well, thanks, Alicia. I mean, I think all across the country and all of us who take care of patients with bladder cancer had a complete, I wouldn't say if the paradigm shifts as much as we had to have a very fast mobilization on how we're going to manage our patients. Because I mean, with the average age of a patient with bladder cancer, well once again, four or five being non-muscle invasive patients being in their mid to late 60s, early 70s and many, many, many in their 80s and 90s. The main question we had to make a decision about as a triage of who needs to be seen, who needs to come to the operating room and who needs intravesical therapy. At Northwestern, we had those discussions with our clinic staff and our nurses and we basically sat down and went through every single patient and said, "Okay, for people who need endoscopy in the office, who needed to have that happen in the next couple months?"

We heard very quickly from our patients, for example, patients that had cystoscopies among the first week where things really hit the US in sort of early to mid-March, the questions they always ask us was do they need to come in for their scope this week? I think in their mind, many folks thought that this is going to be similar to having like a very bad snowstorm where the streets of Chicago are closed and traffic is terrible, but by another week things would get better. That's the immediate reaction is to stay home and not come into the office, but I think the challenge is that's probably not the timeframe for this. This is likely going to be going on for weeks to potentially months. We don't really know when it's safe for someone in their 80s and 90s to be in the hospital.

I can't tell them that it's going to be much safer in May and June, but at the same time if they're getting therapy and they're getting treated and they need their BCG or their intravesical gemcitabine docetaxel, that those timelines need to ... We really think for their cancer that there's a reason why we do the endoscopy and the treatments when we do because we're trying to prevent their cancer from coming back. It's really a risk-benefit balance. Now there's patients who have low-risk disease where we do their cystoscopy once a year and for those patients, by all means, we push those patients time when we think things are going to be much safer. We try to move them to late May to June when we think things are going to be in a much better place.

The folks who are, for example, starting induction, we had a number of patients that we were starting on induction BCG, I think we had four patients we enrolled in SWOG 1602 last week. Those folks were very understanding for it with us and to them, the short-term is getting started and getting their cancer treatment started. These are people that have been four weeks out from their TUR and really wanted to get going for therapy. I mean, literally every single patient has had to go through and make a decision about is the risk worth them coming in? Is that something that we can push out a few weeks? Is this something that we should be pushing out months? Every patient required some attention because on the alternative side of that, when the more people that need to come into the hospital to get intravesical therapy, the more nursing staff we have to keep in our office, the more we potentially expose on a commute in or the people that are just being around other patients and other providers.

There's a risk on both sides of that. We've again, tried to address that each individual patient to make sure that they're getting the best therapy they can, but then also respecting where they're coming from. I've had patients that we, right before this started, we found a bladder mass and they've elected not to go to the OR for a TUR and we say, "Well if you have a bleeding episode at home, that's likely going to mean coming into the emergency room, which is another risk." Every patient's got to make that decision on their own. I've tried to, as best I could have that discussion with them about what that risk looks like. At the same time, be very realistic about our timelines as far as when the operating room is going to be completely open again, and sort of when they're going to be coming into the hospital.

Alicia Morgans: Are there any special precautions that you talk with your patients about if they are getting intravesical BCG or intravesical chemotherapy? Do you have any reason to believe that they would be at a higher risk for complications from COVID-19 for example, or is that something that really patients shouldn't necessarily have to worry about?

Joshua Meeks: We don't have any good any data at all. In fact, if anything, there may be some possibility that they have immunity because they're being stimulated with tuberculosis would potentially be better. We don't have any data about that. Again, I think their biggest risk factor is we're exposing them to a hospital environment and two, is their age, three, the chronicle medical conditions. I think we're sort of looking across oncology and are patients more susceptible? I just don't think we have any good data about that at all at this point. I think the best thing we do, most people obviously in our hospital and that right now are wearing masks. I think we do everything we can from CDC recommendations as far as PPE for our patients, but I don't think we have any data that we're making people at more of a risk other than again, age and bringing them into the hospital.

Alicia Morgans: I think that makes complete sense. I mean, of course, also always counseling these patients to try smoking cessation if it is something that they do. Keeping healthy lungs is probably a good thing to do in this setting as well. Thank you for that guidance. It's very, very helpful. As you're thinking about other populations of patients, actually the one that we share more commonly, the muscle-invasive patient, what are you doing? How was your decision-making changing for this patient population?

Joshua Meeks: Yeah, so a lot of those people that we're encountering for the first time, I would say that there's basically two general situations we're encountering. The first is people who are already in their process of getting neoadjuvant chemotherapy whose surgeries are coming ready. I think those patients, we've had to work with our leadership in the hospital in the operating room to say, "Listen, this is a bit of a time-sensitive situation we're in. We know that if you go longer than eight weeks after chemotherapy, you're potentially at risk for cancer coming back," assuming that people responded. Not to imagine that folks who have persistent disease after chemotherapy, who really need to get to the operating room very, very quickly, so we have those discussions. Every patient kind of gets cleared by both our department leadership and as well as hospital leadership that it's worth that they need an operation in a timely fashion and we're able to complete those for patients.

I think that's the first part of it. Then obviously, keeping them in ... Our floors have changed across the hospitals to keep COVID-positive patients separate from COVID-negative patients. These patients clearly go to COVID-negative floors. We're still treating those patients because their cancer needs to be managed in a timely fashion. We certainly don't want them to have a negative outcome from an oncologic perspective based on what's going on across the country and in our hospital. That's one group that we're trying to as cleanly as we can, keep everything current so we get their cancer treated.

On the other side of it, we're still seeing patients in the office, we're having these e-visits and e-consultations with patients who are newly diagnosed with muscle-invasive bladder cancer. They still need treatment. I think the question that I think both you and I hear a lot is, will chemotherapy make people more susceptible to the virus? Then really I think to me, the best guidance I can give to folks is to get them to you and to get them to your colleagues in medical oncology and have that discussion with them. I would hate for people to not do that because they think they're going to be more susceptible. Where are your thoughts on that, Alicia?

Alicia Morgans: Yeah, so I think that at this point, the guidance that we have from our national and international organizations is that we're really not in a position where we want to compromise cancer outcomes because of fear of what could be in terms of infection. Of course, we do everything that we can to prevent our patients from getting COVID-19 and of course, they also, if they have a really suppressed immune system because of chemotherapy may have a much more difficult time recovering from an infection. I think that we just need to continue to push on with chemotherapy at this point using growth factors in any setting where it's reasonable. Certainly, for older patients and actually for most patients, especially if we're using things like accelerated MVAC that we know are going to cause pretty profound immunosuppression.

The goal is really to get them through chemotherapy as quickly as possible for muscle-invasive disease. Whether it's neoadjuvant as we always try to do or whether we end up doing it adjuvant because of timing around the OR, I think it really remains to be seen. For patients to receive their chemotherapy, I think it will really remain a cornerstone of management and as I said, we don't want to compromise their cancer outcomes for fear of what could be.

Joshua Meeks: Yeah, and I think that sort of fits with our timelines from that honestly fit better into when we're having more capacity in the operating room. The recommendation to proceed with chemotherapy sort of takes some of the stress off of the reduced operating room capacity that we currently have. I mean, not to say that that should guide people to make decisions about care, but at the same time, I think that all the more reason that neoadjuvant makes sense at this time and why that's a better choice. I think all the people who are newly diagnosed, we're sort of getting ... I think we're saying, "Listen, this makes sense. We should be doing this anyway." The alternative is the BCG unresponsive population that we have where there are some patients I spoke to last week who probably need a cystectomy and they've already been through a couple of options and so they're in a little bit of a more challenging position because I have fewer options for them.

Again, I'm thinking, "Well, have we tried pembrolizumab? This probably makes sense if we've not done this yet, to try this in this setting because at least it's FDA approved. You've done many other intravesical therapies, why don't we do this now and give this a last shot?"

Alicia Morgans: Yeah, I completely agree. Of course, these patients don't just come in these two flavors, the muscle-invasive flavor, and the non-muscle invasive flavor. We also have those patients who, unfortunately, have metastatic disease. Are your practices ... I mean those are predominantly managed I think by our group, but we definitely co-manage a lot of those patients because they end up having urologic complications or hematuria or whatever it is. What are your thoughts on that population?

Joshua Meeks: Yeah, I mean, it's interesting. I've spoken to a few people in the last week again, that are locally advanced to metastatic and I don't know if you're detecting it, but we're certainly seeing a lot more of, "I don't know if I want to do anything at this point." They have options and they're saying, "Well, I don't know if I want to proceed or look at systemic therapy if that's going to make me more susceptible." Again, I think it's time to have a better reflection of the goals of therapy and really I think that there are still many good options that we have. I definitely think that it changes the discussion and it's a better time for us to try and rally together to treat our patients with bladder cancer.

Alicia Morgans: I agree. It's interesting because I even have patients who, like you said, are concerned about getting checkpoint inhibitor therapy. They're concerned about drugs that may increase their immune response. They're concerned certainly about drugs that may cause neutropenia. There's just a general unrest and, and fear. I know and you know what happens when we don't treat metastatic bladder cancer and for a majority of patients, it's a relatively short timeline and it can be a relatively poor quality of life in that timeline. I think that we do encourage patients to at least consider or try therapy, but they are complicated conversations. One other population that I failed to mention earlier, that we also work together to care for are those muscle-invasive patients who end up getting chemoradiation. What are your thoughts on those patients, especially since that radiation does bring them into the office, to the radiation facility at least daily for weeks?

Joshua Meeks: Yeah, absolutely. Again, I try to have the discussion outside of the COVID-19 context to say, "Okay, what are your goals? What are our long-term wishes and how do we want to treat this cancer, and what options do we have on the table?" Again, I try to weigh surgery and chemoradiotherapy equally patients as far as bladder preservation. We try to talk outside of this. I haven't seen in folks that necessarily are increasing or decreasing their interest in that. I think most patients are very interested in that possibility, and so we have those discussions with them. I think again, they're more concerned about the chemo-radio sensitization that is given to try to make the radiation work better. They're concerned more about that than rather the exposure in the radiation.

Again, like you say, it's a, it's a daily sort of trip in. I think most people are really appreciating the social distancing. They're on board with not coming into the hospital and so like you say, try having to come in daily. We were lucky that we have a strong network of providers across our system where we have facilities across most of Northern Chicago or Northern Illinois, where patients can go to get therapy. Many of them quite were very also lucky that for example, we have our bladder preservation trials like SWOG 1806 open, and so if patients want to do that trial, they can often enroll at sites outside of our central region. I think having the ability to have a larger network and people get good care and talking to our providers throughout there. I think that's potentially decreased some of the anxiety that they don't have to go all the way into the city every single day that they can get their treatment potentially closer to home. Again, we try to, as best we can decrease the anxiety around those visits if possible.

Alicia Morgans: I agree. I think anything we can do to decrease anxiety, especially as we learn more and treat more patients in this particular setting, will be helpful to patients and certainly helpful to other providers. I sincerely appreciate you sharing your expertise today. I think that I certainly have learned a lot and as we continue to evolve in our understanding and our practices, we'll have to have you back on to share some more insights. Thank you so much for your time today.

Joshua Meeks: All right, Alicia, thank you, and stay safe.

Alicia Morgans: You too.