Alicia Morgans: Hi, this is Alicia Morgans, Medical Oncologist and Associate Professor of Medicine at Northwestern University. I am so excited to have here with me today, Dr. Petros Grivas, who is a Medical Oncologist and the Director of the University of Washington Medicine's GU Oncology Program, and an Associate Professor as well there at the University of Washington in Seattle. Thank you so much for being here with me today, Petros.

Petros Grivas: Thank you so much, Alicia, for having me.

Alicia Morgans: Of course. So, Petros, we're really kind of trying to connect to folks to hear voices of clinicians, of leaders across the country, around the world, who are dealing with the COVID-19 pandemic right now that is hitting all of us, as well as our GU oncology patients. And I would love to hear your thoughts, both from an outpatient perspective as well as how it's affecting your patients on the inpatient side. And what you see as problems and ways to overcome. What are your thoughts?

Petros Grivas: Thank you, Alicia. Well, I agree with you. We're living in a pandemic global crisis here, and we try to learn as we go, day by day, hour by hour, minute by minute. In medicine, you always get information changes very quickly, but what we're experiencing these days is, I think, once in a lifetime. Having said that, I think one of the take-home messages for the audience is, stay informed and keep open the channels and the lines of communication, and send information globally, along the channels of communication across each other, because we can learn from what each other is doing.

In that context, I think there is a clear need for data. As the situation's evolving rapidly, we don't have enough data to guide our decisions day by day. So we need data publications, we need communication, and we need even anecdotes and cases to be searched, so we can get some input on how we can handle things. In that context, I just want to give a shout out, in the cancer registry, that we're developing actively real-time with colleagues from the university and Vanderbilt University in Nashville, Dr. Jeremy Warner, Brian Rini, colleagues at the University of Austin, and Fred Hutch, and many other institutions [inaudible] The Cancer Letter just came out today, outlining this important initiative to get people to fill out this registry from different cancer centers so we can learn together many bits of information regarding cancer and COVID.

Having said that, we have to make decisions already in the clinic. So a few, I would say, kinds of rules of engagement regarding the outpatient clinic. In our cancer center we, early on, even a few weeks ago when the whole story started, we decided to implement an instant command strategy and we have a very well structured, I would say, planning. We have people in specific roles and every few hours a day they provide updates of where we are and what we do. One of the first things we try to do is to put some people in the main entrance of the cancer center screening everybody who comes in, provider or patient, about symptoms. Do you have symptoms? Yes or no? If yes, what type of symptoms you have? And if someone meets a criteria then they are being triaged to the appropriate area of the cancer center for testing, swab tests, for COVID-19. At the same time, the provider and the team are being notified that their patient is being tested and then depending on that, the patient might or not come upstairs to be evaluated in the clinic. So that's a nice kind of screening and triaging system implemented.

Now, we try also to create a mechanism that we can address mild or moderate issues in the ambulatory cancer center, in the outpatient setting, by having a fully staffed infusion room, pretty much trying to keep people away from the emergency room if we can. This, of course, requires planning, resource, and infrastructure, and we're trying hard to, as much as possible, to address those issues for people who do not need to go to the emergency room to be monitored in outpatient.

Being a little bit more specific regarding GU cancers, I think there's a lot to be said about how to manage those patients. But just a few examples, we are all struggling I think worldwide to define which procedures and surgeries can be considered elective and therefore can be postponed, versus procedures that need to be happening right now and are urgent or emergent. So I think it's significant variability in those definitions. The American College of Surgeons recently put out some guidelines and I think it's very important, and a take-home message for the audience, for each institution to develop some kind of algorithm or guidelines with which procedures they are considering elective and which are not.

To give you an example, we have patients with high-risk, high-grade urothelial carcinoma that require radical surgery, we say aggressive cancer that might progress in this patient, we try to move on with surgery if they're due for surgery as planned before. However, if the other procedures are elective and not requiring attention, those could potentially be postponed. And I think it's very important for patients and providers to have this dialogue and discussion case by case. So patients can ask the questions and make an informed decision after talking to providers which procedures are urgent and what can be postponed.

The same thing with visits. So we try hard to keep people away from the cancer center unless they need to come in. In that context, if someone needs to come in for a treatment or an urgent evaluation, they come in. But if someone has a longterm follow-up that does not require inpatient visit, oh I'm sorry, an outpatient visit at the cancer center, then we can try to utilize telehealth in order to evaluate these patients through telehealth, telemedicine appointments, or phone visits in some situations depending on credentials. So we can try to keep people at home if they can safely be managed that way. Of course, we can talk I believe more if you want about specific treatment considerations. But that's kind of an outline overview of how we think about it.

Alicia Morgans: I really appreciate that. And I think for patients and also for clinicians who are listening, just to really focus and think about what is absolutely necessary to pursue right now in terms of inpatient admission, surgical procedures, or other procedures. If these are routine cystoscopies for example, where we're just sort of assessing over time and it's been maybe a few years since definitive therapy, maybe with chemoradiation for example, for a patient with muscle-invasive bladder cancer, perhaps we could just delay the cystoscopy until the summertime where it may be a little bit after the urgent need of potential inpatient equipment and other things.

But there are going to be situations where patients have new metastatic disease and we need to make treatment choices now. So what are you thinking now, Petros, when it comes to patients who are coming to you with new metastatic urothelial cancer, for example? They are facing potentially a decision between chemotherapy, an antineoplastic agent, that does cause immunosuppression or immunotherapy, checkpoint inhibitors for example.

You know, we do have the guidance from the FDA that says that if a patient is eligible for antineoplastic chemotherapy, that is the way to go. And that guidance was really given to us in a non-pandemic situation and it's really based on clinical trials that suggest that first-line checkpoint inhibitors are less effective, have a lower response rate than first-line chemotherapy. So what are you doing now in your clinics? And not to put you on the spot, and I'll go first just so I assure myself that I'm not putting you on the spot, at this point I'm still using the guidance that we have from the FDA, but counseling patients really carefully that if they are chemotherapy candidates, they need to be super cautious about this.

And if they have reservations and then choose and hope to go for checkpoint, we can continue to have that conversation. But you may be facing more of those decisions than me because I think you have a larger bladder cancer volume. So what are you doing in your clinic?

Petros Grivas: Alicia, these are great questions and real-time problems. I think it's very important to have this individual discussion to each patient with each case one by one, because as you know and implied, one size may not fit all. I think, for now, I agree with you. I follow this FDA guidance. And I try to implement evidence-based medicine but council the patient of, you know, these are real risks of COVID-19 exposure, immunosuppression appears to increase the risk of infections and complications.

So we have to balance that, and it's every discussion I have with a patient now includes COVID-19 considerations in my balance of risks and benefits. And I document that in each note in the medical record. I think specifically, to answer your question directly if someone is fit for cisplatin and has metastatic urothelial carcinoma, I tend to still stick with the guidelines and consider after the balance discussions of risks and benefits, cisplatin-based chemotherapy for those who are fit for cisplatin, metastatic disease, first-line.

If someone is not fit for any chemotherapy, then either clinical trials or checkpoint inhibitors are the obvious answer and we can talk about clinical trials in a second. But if someone is kind of borderline, and you can argue either way, between carbo/gem and checkpoint inhibitor, then you can answer do you have PD-L1 assay available which you know helps us overall in this dilemma.

If you don't have and it's hard to get it within a reasonable amount of time, then you can potentially inform your discussion with the COVID-19. However, I don't think that, again, one size fits all, because we don't know exactly, we don't have the data, right? How its treatment influences the risk of complications. Immunotherapy for example, in theory, increases your immune system, but we don't have good data. How this interacts with COVID-19.

So far, to answer your question, I'm trying to counsel a patient's risks and benefits, but I tend to treat them by using the guidelines that I have been using so far, which is based on the cancer risk. And I'm using chemotherapy and immunotherapy based on the current evidence-based indications.

What has changed is that the discussion includes the COVID-19 risk. Even in the neoadjuvant setting, someone can argue, do you give neoadjuvant chemotherapy cisplatin-based? In a fit-based sense? Or you go straight for cystectomy? And that's a big debate. So far, and this is just my personal bias, but people may have different opinions, we have significant challenges even getting people into the operating room. So I tend to have a balanced discussion with the patient, but I tend to offer cisplatin-based neoadjuvant chemotherapy in this curative-intent setting for those who are fit for cisplatin.

And again, after the counseling, and then consider surgery after neoadjuvant chemotherapy. But again this happens case by case. We don't know, as I mentioned, regarding immune checkpoint inhibition. The other question is, you know it's a very important therapy and we use it very frequently in GU cancers, specifically in urothelial cancer, kidney cancer.

If someone has a near-complete response and they are two years out on therapy, you know we'll have the debate. Do we continue beyond two years? Or we stop? You know, in the era of COVID-19, again we don't know, we have no data, but that may be another factor to consider to potentially give them a treatment break if they're in complete response, two years on a checkpoint inhibitor, give them a holiday of treatment, reevaluate as a consideration. Again, after you discuss the base on a case by case.

The other thing is do you utilize our standard dosing? Do you do pembrolizumab every six weeks? As far as I know, the application of the company to the FDA, I think it was not approved. So the two-six-week pembro is not approved as far as I know, and our pharmacy cannot use a blanket approval for that.

So for now, we stick with every three weeks. But the question comes, do you skip a dose in patients with good disease control so they can come less frequently to the cancer center? These are real questions. We don't have the answers, but it's a case by case discussion with each patient, how comfortable they are to come over.

As an overall theme, especially in patients with good disease control, we have informed discussion about telehealth and if they're worried, we may try to keep them away from the cancer center at least for a reasonably brief amount of time.

Alicia Morgans: I completely agree. And just to round up the discussion with a quick comment on clinical trials, you alluded to this as you were talking, our clinical trials, certainly non-therapeutic trials have been placed on hold. Therapeutic trials are really at the discretion of providers and only in the best interest of patients, as they always are, but really kind of kept to a minimum. I'm curious to hear how things are for you in Seattle.

Petros Grivas: That's another fantastic question, Alicia. So I think that it comes down to each individual institution following the guidance from authorities like the FDA, which recently published some guidelines. Considerations from ASCO, that published frequently asked questions.

In our center here, the university took the approach to temporarily halt some, meaning a portion of research activities, especially for trials that do not appear to have a very high chance to benefit patients. For example, the Fred Hutch Cancer Center came out and said Phase I studies, dose-escalation, mostly safety-seeking trials that are not prominently aiming to benefit the patient may be on hold for now, as well as Phase III trials that have an equivalent option of trial. If you, for example, compare treatment X versus standard of care, then you have a standard of care available, so this patient may go to the standard of care. So those trials may be potentially on hold, and other trials may continue if the trials we think they'd benefit the patient, and it's a good option for the patient, we may continue. For example, Phase II studies for patients who need treatment.

So what do we did in our group is we went through each trial one by one in our GU group, and we put out the trial, discussed as a group, but the benefits or risks, and we made a table, even yesterday we did that, and which trials continue accrual, which trials suspend accrual of new patients. However, all of the trials, we continued to take care of the patients of the old trial. So we continue, of course with precautions, study procedures that are unnecessary for patients who are already enrolled.

Alicia Morgans: Agreed. Well, thank you and thank you for sharing your experience and giving your guidance for us to understand how you're thinking about things in an outpatient clinic, at the inpatient clinic, with clinical trials, how you're making treatment choices, or at least having really informed conversations with your patients. We so appreciate hearing how things are for you, knowing that it is not easy where you are in Seattle, and even less easy I guess I should say, in the upcoming weeks. So thank you for your time, for your expertise, for your guidance. And I hope that you and your loved ones stay safe. Thank you so much, Dr. Grivas.

Petros Grivas: Thank you so much, Alicia, and everybody stays healthy and safe out there.