Alicia Morgans: Hi, my name is Alicia Morgans and I'm a medical oncologist at Northwestern University where I have the pleasure of working with a friend and colleague, Dr. Josh Meeks, who is an Assistant Professor of Urology and Biochemistry and Molecular Genetics. We work together in the Polsky Urologic Cancer Institute and I am so appreciative that you're coming to speak with me today, Josh, about the BCG shortage that's been hitting everyone.

Joshua Meeks: Thanks, Alicia. I really appreciate you hitting this topic. It's an important thing that we can still continue to talk about, what to do in this setting and if you remember, we're probably anywhere from 10 to 12 months into the point where many places have not really had adequate BCG. We hear updates that there may be more, potentially, BCG on the way. I think the way that we've really tried to address that, I think there's two things that most urologists can do.

The first is figure out do patients really need BCG? Because BCG is really only recommended for high-risk bladder cancer and that's carcinoma in situ T1 tumors, or very bulky multifocal Ta high-grade tumors. So I think if you look at the AUA and the EORTC risk categories, high-risk is about 20%, maybe 25% at most. So if we restrict the use to the highest risk patients, I think that's the application of the drug is the first thing.

The second is for those that are intermediate risk, which is a smaller Ta high-grade, those are patients that we usually would give intravesical chemotherapy too, so gemcitabine or mitomycin, and I tend to, if they have recurrence on those drugs, then I would go ahead and consider them for BCG. But if we just use the drugs for the patients that are at the highest risk, I mean, if we apply BCG for the high-risk patients and chemotherapy for the others, I think that's going to take care of a lot of patients. Because if you look at the shortage, the shortage developed right around the time where we've really implemented our guidelines from 2016 which is recommending considering maintenance BCG, and the number of bladder cancer patients hasn't increased. There hasn't been a production shortage per se. I wonder how much of this is an application shortage. We're trying to use more BCG because it works, but are there other options we should really consider for patients, especially those who have intermediate-risk bladder cancer that can be treated with other things?

Alicia Morgans: So Josh, are there studies that are trying to figure that out? Because from what I can understand, it looks like Merck, who's the sole manufacturer of BCG, and the reason I think that we were kind of encountering this shortage, you know, there's only one manufacturer, they've actually increased their production by quite a bit. So recognizing that this something that may be here to stay for some time, are there studies that are looking, like you said, at alternative opportunities for some of these patients?

Joshua Meeks: Yeah. And the real question that people... So there's a lot of folks trying to think about both the intermediate and high-risk space for the BCG-naïve space and how you develop those trials. Because I think the big problem with BCG that we faced from a scientific perspective is it works really, really well. And so you have to design something that's going to go head-to-head with BCG and do better than BCG. But then the problem is you're not always guaranteed you're going to get BCG, right? So if you're thinking about designing a rather large study that's going to be challenging BCG, you have to have enough access to BCG to carry out the study.

Alicia Morgans: Absolutely.

Joshua Meeks: So there's definitely some international trials going on right now. So for example, POTOMAC is a trial where it's comparing durvalumab, BCG plus durvalumab, to BCG alone. So there are those studies going on and there's definitely an interest in people doing that. But I think the challenge of structuring a trial, going head-to-head with BCG when you know that you may not have access to it. So I would say that those trials are still in their early infancy for things that are "BCG replacements" at this point.

Alicia Morgans: Okay. Well, any guidance other than really choosing the right patient and then trying to use your BCG, the BCG that you have on hand, use it judiciously. Any other guidance for clinicians and teams who are trying to just really stretch the BCG that they have to cover as many patients as possible? What else can they do?

Joshua Meeks: Well I think number one, as surgeons, we should continue to do a great job. I mean to me, I would argue if you have the option to do blue light cystoscopy, you can see the carcinoma in situ better. All the data suggests that you potentially are doing a better TUR with blue light cystoscopy. So that surgical resection of CIS, we don't know what that contributes, but it certainly affects recurrence rates. So you can do a better operation. I think the second part, obviously, we're heavily involved in the SWOG 1602 PRIME study. That study was temporarily on hold for several months, but now it's open again. So I mean, it's a 900 patient study, we're about 500 patients into it. So there are 400 more patients that can go on that trial. It's a non-inferiority study compared to Tokyo-172. It's not meant as a registration trial for Tokyo-172 but in the era of shortages, as much as you can do to give an option, you never know what that's going to longterm do.

Alicia Morgans: Absolutely. So before we wrap up, I just want to hear your thoughts. I know that the community around bladder cancer patients and the clinicians, the urologists, and others who treat them have really come together around this particular shortage. I know BCAN is doing all that they can to support clinicians as they are trying to move forward, and of course, support patients as they're trying to figure out how to best move forward. AUA, SUO, LUGPA, any comments on the outpouring, really, of groups that have come forth to really try to make a difference in this shortage, expecting that we don't have an easy fix for it in the short term?

Joshua Meeks: Yeah, I mean I think the big thing that I've seen around our region is that people pretty selflessly send patients to centers that have ample BCG. You really don't see that as much, or I had not seen that anywhere in urology as I have with this, where people know where the BCG is and if there's high-risk patients, trying to get them into either trial or get them in for consideration of getting the standard of care BCG that we have in stock. So I've been impressed by our colleagues here in the Midwest that are pretty good about sending patients out instead of, for example, trying to treat them suboptimally if they're a high-risk patient, they really do try to get them to spots with BCG.

Alicia Morgans: Absolutely. So we're going to continue to do what we can to deal with this shortage, continue to get patients the care that they need as we can see that people are already doing, they are adapting to this shortage. It doesn't look like it's going anywhere. But I love the message of number one, be a good surgeon, take care of your patient, use blue light if that helps, do the best resection that you can do. Get your patients to BCG, they will come back to you. But get them the BCG, the treatments that they need in the short term. And it sounds like we're doing that and work is being done to find alternatives for BCG. It's just going to take some time and we need to continue to come together as a community to make it happen. So thank you so much for your time and your discussion on this, Dr. Meeks, I really appreciate it.

Joshua Meeks: Thanks again, Alicia.