Alicia Morgans: Hi, this is Alicia Morgans, Associate Professor of Medicine and GU medical oncologist at Northwestern University in Chicago, Illinois. I am so pleased to have here with me today, a friend and colleague Dr. Toni Choueiri, who is a Professor of Medicine at Harvard Medical School and Director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute. Thank you so much for being here with me today, Dr. Choueiri.

Toni Choueiri: Thank you, Dr. Morgans.

Alicia Morgans: Wonderful. Toni, we spoke a number of weeks ago as COVID-19 was starting to influence our day-to-day practices. Certainly, as the director of the GU Oncology group at the Dana-Farber, you had a lot of insights on how this was impacting day-to-day care and certainly your colleagues at the center. Now that we are in the next phase, or many of us are, I have really appreciated seeing that you and the team have put together a set of clinical guidelines to help yourselves and others think through how we might approach the treatment of GU cancers in the setting of COVID-19. Can you tell us a little bit about why you put that together and what it took to get all of that work done? Certainly, I'm sure a lot of Zoom calls?

Toni Choueiri: Yes. Well, thank you. Actually, really, we're very proud of this document. And it stems from the fact that COVID-19 pandemic has put significant stress on the health system overall, and on oncology. We really were forced to adjust our practice because we want to continue to optimize care for patients with cancer, but at the same time keep the patient safe and keep the healthcare worker safe. And it stems from the fact that originally, from all the original research as you know that is coming at hundreds of documents, it's sometimes not being reviewed. And with cancer and COVID-19 that these patients may be twice as likely to die even with no comorbid condition. We don't know yet what is the reason for that. But why can't we continue to optimize our care and adjust specifically for our patient needs?

So we came up with a document, we know the four diseases well, kidney, bladder, prostate, and testis cancer. And we know the guideline, how to follow the patient, what therapies to get, what surgery, what radiation at what time. But actually, can we take an approach where we adjust these visits and adjust overall the schedule of the patient? So there was some general consideration that we developed. First is to avoid, if possible, using immunosuppressive steroids because we do believe that these patients that are immunosuppressed, at least our GU oncology patient, may be at higher risk with COVID-19, especially with the toll it takes on their immune system and the viral entry and all that pathology. Then the biggest thing is, how can we minimize hospital exposure in providing great care? And when can we have an approach that is sensible to the first clinic visit and pursue therapies with fewer infusion cycles while increasing the use of telemedicine? So for every disease, we took those two potential changes into consideration.

Finally, for patients receiving chemotherapy that are associated with neutropenia. So think about docetaxel, cabazitaxel, BEP chemotherapy, and testis cancer, how should they receive GCSF support and self-quarantine as much as possible for medical visits because these are the patient at higher risk? Then we developed these guidelines with these three principles in mind for each of the cancers. And I'll be happy to talk to you through these or perhaps provide you the document that we worked on.

Alicia Morgans: Well, absolutely we will post a copy of these guidelines for the listeners to download and review, and potentially implement it to whatever extent is appropriate at that their own sites. We'll definitely do that. But let's walk through some of the highlights in each of the tumor types so that we can get at least a high-level understanding of some of these. I appreciate, certainly, the general considerations that we've discussed. But let's go through each of them in terms of the specifics for the tumor type just to lend a little more guidance on this audio recording.

Thinking about bladder cancer first, certainly there's non-muscle invasive disease and then there's muscle-invasive disease, and the guidance is very different for both of these. When we think about bladder cancer in general, are there some highlights that you wanted to point out?

Toni Choueiri: Yeah, definitely. So for bladder cancer, and just to let you know, when we did this, it's a multidisciplinary approach. And while the medical oncology led these recommendations, this was in perfect harmony with the Brigham and Women's Hospital with our GU radiation oncologist and our surgeons because work in a multidisciplinary fashion. So for bladder cancer for example, Dr. Morgans, for low-grade patients and even intermediate both of intermediate-risk and low-risk for noninvasive bladder cancer, we suggested extending the intervals between surveillance cystoscopy and maintenance regimen. And we go case by case with patients. With high-risk disease, we try to keep the guidelines for cystoscopy the same. For muscle-invasive bladder cancer, this generated a lot of debate because we know that the standard is neoadjuvant when possible cisplatin-based chemotherapy. So on one hand you could say, I do want to delay a bit radical cystectomy despite its curative radical cystectomy and definitely insist on neoadjuvant chemotherapy, especially in situation where it's not clear enough. And I think this was our approach especially with less and less surgeries happens at the hospital.

On the other hand, we have seen people coming up and saying, we should not do chemotherapy neoadjuvant approaches or adjuvant approaches that give you a survival benefit, but the survival benefit that is in the single-digit and we should go directly to surgery. But then in the era of COVID-19, if you think all the hospital is full of patients with COVID-19, is it the time to do radical cystectomy that is a morbid operation in general with several days in the hospital, or I would say operation associated with certain morbidity rather than declaring it morbid? So we have tools of use here, but we have decided that the neoadjuvant approach makes a lot of sense.

For metastatic disease, certainly, when we use dose-dense MVAC or gem/cis, we insist on avoiding myelosuppression with gross factor. And I think this was very, very important. With adjuvant disease, again, back to muscle-invasive bladder cancer, we delayed and made sure that treatment could be initiated up to three months after radical cystectomy. So these are all guidelines for all of these patients outside their treatment, their systemic treatment. We are trying for muscle-invasive and metastatic to space the imaging a bit from very good with three months to four and six months. When we discussed this as a group, all of us, there has been a lot of back and forth and agreement that we have to be as flexible as possible, but we have an overall agreement. So, that's bladder cancer in a nutshell.

Alicia Morgans: Absolutely really important principles. And I think it's really interesting to see that one of the overarching themes throughout this section is really limiting exposure of patients to the healthcare system as much as is safe. Trying to space out the intervals for imaging, as you said, there are some adjustments that might be made with administration of IV medication suggested. So I think that's really an important overarching theme. Then one other theme that was mentioned, and this is probably something that applies to most of our GU oncology patients. So of course, not necessarily those patients with testicular cancer, for example, who are really being given chemotherapy with curative intent in mind for most of those patients, but also to acknowledge when patients need to consider hospice as an option, which is something that's important always, but particularly in the setting of potential infection.

I was talking to someone yesterday who said patients who had been treated without curative intent, really palliative therapies, and who ended up in the hospital hadn't necessarily considered hospice or that they may not make it out of their cancer situation, let alone their cancer situation in a setting of a COVID infection. So acknowledging that in the guidelines, I think is a really important piece of what you put together.

Toni Choueiri: Yeah, thank you. We haven't touched base on the situation where you need hospice with a patient and how are you going to be able to do that with telemedicine, or a Zoom call cuts it. I had an experience, I luckily have to say I haven't needed to do that. I had a couple of patients hospitalized. I was able to talk to the families, but I know a couple of my colleagues were able to have Zoom calls with all the family calling in. And actually, what was reported later on that it was a very comfortable and very good discussion with the patient where all the family members were able to chime in and it was one-on-one.

I think that human interaction remains very important, the face-to-face is very important. But there is something to be told by telemedicine and the Zoom and the other platform that when you have a laptop or a desktop and the patient has it and you're just one-on-one, I heard a lot of comments that they feel even more linked and more attached and more one-on-one with their physician. Which we know that the past few years with the electronic medical record and running around, this has not been able to do. But maybe now there is a more, maybe in some situation is better and the focus is one-on-one more. So this is just the silver lining of this whole horrible pandemic.

Alicia Morgans: I'm glad to see that there are some, and certainly telemedicine is one of the silver linings that has consistently been coming to the fore in these conversations. So I certainly agree. To move on though, to our next disease site, one that is near and dear to your heart, a lot of the work that you do is really around patients with kidney cancer. What are your thoughts in terms of the guidelines and how did you and the team approach guidance for patients with kidney cancer?

Toni Choueiri: Yeah, I agree. We know that small kidney masses defined by three or four centimeters could have multiple treatment options from surgery to ablation to active surveillance. So in the right patient, we are pushing for active surveillance more after of course discussion with the patient. I get a lot of calls about that. So of course with the help of our colleagues, this is happening. Sometimes even without the biopsy and really small kidney masses, two centimeters or less because we're going to repeat the imaging at some point, hopefully soon. For high-risk patients, those are the ones that just had surgery outside or had surgery around or before the pandemic that are coming for adjuvant treatment, we still have trials open. Our trial portfolio with Dr. Taplin at the lead has been open and we have enrolled patients on trial and continue to. However, with the understanding and taking into consideration the number of visits, what is the trial in question and the other consternations. Sometimes the patient just doesn't, and we agree with, doesn't want to be exposed.

But back to kidney cancer high-risk, do we do adjuvant therapy on or off trial? We know that no adjuvant therapy in the history of renal cell cancer, higher risk, have shown an overall survival benefit. So if a patient here is coming to see us for that, this will be our main explanation to strongly suggest following them with imaging rather than giving them adjuvant sunitinib, which is approved in this disease but would require more interaction with us face-to-face and all the side effects that can issue. So this was emphasized. For metastatic disease though, I think here we have taken an approach that is quite unique because we know today's therapies are not yesterday's therapy and certainly not going to be the therapies of the future. How the field is moving so fast, but in the center part of the field actually is immune checkpoint inhibitor and you know very well, we all know that these could be associated with an immune-related adverse event. Especially when you use two drugs instead of one, that will lead to corticosteroid with all the immune suppression.

I think around 20% is a good number for nivolumab and ipilimumab. So the question, would you do one drug plus one venture of tyrosine kinase inhibitor and what do you do for your patients on trial? So we have taken an approach where we have an open conversation with the patient about the side effects and the potential use of steroids, which is the thing really that comes to mind. You'll be surprised how people may react when you show them the efficacy and the adverse event profile. So a lot of our patients would be comfortable more so with a TKI or TKI plus IO.

Another issue with being around cytoreductive nephrectomy. I think most of us agreed here that potentially proceeding to systemic therapy initially rather than the hospitalization with surgery, it's not an overnight surgery, could be tried in this era of COVID-19. And for these IMTC risk groups that are favorable patient without risk factors, we know that observation and active surveillance is an option. So we are favoring this in patients with low volume disease if the physician and the healthcare provider and the patient are comfortable with. So this is in a nutshell, kidney cancer for you.

Alicia Morgans: Great. Moving on then to prostate cancer, thinking about localized prostate cancer and advanced cancer, what were your general recommendations for that?

Toni Choueiri: For that, Dr. Morgans, with localized prostate cancer, we know how many patients may not need therapy. And in those borderline cases where patients really have low-risk but they have maybe one feature that doesn't make them low-risk including sometimes anxiety and others, we are really trying to, as much as possible, discuss active surveillance on patients with rector followed with BSA and MRIs and keep a close eye on them. We know that also patients with unfavorable intermediate-risk or high-risk prostate cancer, perhaps here, especially if the OR is not open or surgeries are not happening, perhaps it shifts towards radiation and hormone here where we can start by one injection of LHRH agonist and then move to radiation or delay a bit radiation until months, instead of months two or three to months four, five, and six. Also, could be entertained without concern for a poorer outcome.

I think these are very reasonable choices. We do have actually also a neoadjuvant with Dr. Taplin, neoadjuvant Phase III trial by the name of PROTEUS, which targets the patient with high but also very high-risk prostate cancer plan for surgery. We're still really screening for that trial and discussing the risk-benefit of this approach with a patient. Biochemically recurrent prostate cancer, and as we know based on the PSA doubling time and other parameters, sometimes we can wait a bit to start something. So we're following that philosophy in a way rather than immediately starting something, especially if it's only a matter of weeks. So that's in a nutshell, and coming to metastatic prostate cancer, especially castration-sensitive prostate cancer, where of course the choice is going to be between androgen deprivation therapy with LHRH agonist, but also between chemotherapy docetaxel or AR antagonist.

Here, we're leaning towards AR antagonists, especially with the potential for the docetaxel to induce neutropenia and the hospital visit. So this was a no-brainer for us a bit, but we have to also discuss the data with docetaxel and have a discussion with the patient and perhaps defer docetaxel until later, or give definitely AR pathway inhibitor over docetaxel, even in a chemo-fit patient, and especially in the patient with advanced age.

I didn't mention that to you, but all the data I would say, I hate to say all, but the vast majority of data in cancer patients, non-cancer patients about COVID-19 risk of death and risk of morbidity and severe complication and ventilation seem to have age as a very important risk factor. And there are many, many reasons for that. There are physiologic reasons, but there are reasons related to COVID-19 itself. There's a lot of papers out there showing that maybe elderly people have higher risk too in their lung receptors, which puts them at risk, same as smokers for more viral entry. The data is not very clear, but at least age comes up always. When we think about these guidelines, take age into consideration. So a 45-year old that may insist on docetaxel, who is metastatic hormone-sensitive, prostate cancer is not like a 90-year-old or 75, 80-year-old, who in theory is chemo fit when you look at them, but may not understand that in the era of COVID-19 age is such, such an important factor. So we try to look at that into detail.

Finally, for metastatic castration-resistant prostate cancer, where docetaxel, cabazitaxel, and others are important treatment, we use growth factor in a very judicious and reasonable fashion. Even when the guidelines say that this patient has enough bone marrow reserve, you should not give them growth factor, actually, we use it. We cannot afford a myelosuppression and [nephro brand 00:00:22:55] neutropenia in this situation. Whether it exposes them to COVID-19, it lowers their immunosuppression or whether it leads them to be hospitalized. So that's in a nutshell, and I'll stop here for prostate cancer.

Alicia Morgans: That is quite a tour de force of prostate cancer. Thank you for considering all of those things and certainly sharing them. And then to just conclude, the group also made comments about testicular cancer. Speaking about age, this is one of our younger age group populations typically, and usually, they are being treated or monitored with the intent for cure or in the belief that they've already been cured for patients who are following surveillance. So can you share your thoughts on testicular cancer?

Toni Choueiri: Yeah, I think with testicular cancer here, I think the most important thing to know with metastatic testicular cancer and that's probably out of our eight-page document, that's probably one-third of the pages. Because therapy for curative intent with metastatic testicular cancer should not be delayed and growth factors should be given. So here you can cure people. This is the chemotherapy, this platinum-based chemotherapy that cures people even with brain metastases from testicular cancer. So we're not going to play around here. Therapy needs to be on time, needs to be with a growth factor. However, with clinical stage one seminoma or non-seminoma after orchiectomy, we know that surveillance in both seminoma and non-seminoma is an option. So we're going to push that over adjuvant therapy and regardless, really of risk group.

For a patient that, we're talking more about stage two or three and metastatic germ cell tumor. The question is, should we give bleomycin a yes or no? We could give bleomycin, but we feel that it should be excluded to the degree possible. A patient should be given four cycles of BEP or four cycles of VIP. So rather than four cycles of BEP, four cycles of VIP, rather than three cycles of BEP four cycles of BEP, because of bleomycin potential lung toxicity. And if that's the case and the patient loses lung reserve and they have COVID-19 in addition, and they go to the hospital, all that we believe having bleomycin on board is not the best thing. So we're trying to avoid bleomycin knowing that the vast majority of testicular cancer patients tolerate bleomycin result in a lung problem. But in this situation, it may be really reasonable to avoid it.

Alicia Morgans: Well, I think these are all very sound recommendations, and I appreciate so much your willingness to share them with everyone, both in this audio podcast, but also as a document for individuals to review. Just briefly as we wrap up, do you see this document potentially evolving somewhat over time, or maybe having parts of this really applied during intense periods of COVID outbreak in areas whereas other things may be less important if COVID is present, but maybe just smoldering in the community rather than being so intense? Is this something that you anticipate may change over time?

Toni Choueiri: Yeah, I do think, it's almost like a living document because hopefully at some point, this nightmare will end and we're going to redeploy and hopefully we're going to redeploy in phases, not just deploy suddenly life like normal because it's not going to be normal for a time. Then we're going to go back to what we did previously and hopefully, we'll update the document little by little and there'll be versions before reverting back to what we did before COVID-19, let's say in September 2019. That's one. Second, we cannot exclude the fact that we may have another surge or another pandemic or we don't know if this is going to be like the flu where it's going to come every year with or without a vaccine. And what if there are clusters in places even if these places are sealed and they're contained, but still they involve a lot of patients with cancer. So perhaps this, we can revert back to that document at that time. So the answer is yes, every day we're changing things.

Alicia Morgans: Well, we look forward to referring to this document, considering it in our own practices, I'm sure. We also look forward to the updates that will come over time. Thank you so much for all of the efforts you and the team put forth to construct this document. And thank you also for sharing it with everyone so that we can have some understanding of suggested best practices. Thank you for your time today as well.

Toni Choueiri: Thank you very much. And thank you UroToday and Dr. Morgans and all your staff are always updating the GU community on the latest and having such a dynamic platform.

Alicia Morgans: Thank you.

Toni Choueiri: Thank you. Have a great day.