Joshua Meeks joins Alicia Morgans to review his approach to cystoscopy using blue light and Cysview®, and how to best choose patients that will maximally benefit from that kind of technology. Dr. Meeks and Dr. Morgans also review the new approval of pembrolizumab in the BCG unresponsive high-risk non-muscle invasive bladder cancer (NMIBC).
Josh J. Meeks, MD, Ph.D., Assistant Professor of Urology and Biochemistry and Molecular Genetics at Northwestern University Feinberg School of Medicine, Chicago Illinois
Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.
Read the Full Video Transcript:
Alicia Morgans: Hi, this is Alicia Morgans, Associate Professor of Medicine and GI medical oncologist at Northwestern University in Chicago. I'm so excited to talk with a friend and colleague, Dr. Joshua Meeks, who is an Assistant Professor of Urology and Biochemistry and Molecular Genetics, has a lab, is a practicing urologist, just an all-around extraordinaire. Thank you so much for talking with us today, Josh.
Joshua Meeks: Thanks, Alicia, great to be here.
Alicia Morgans: So Josh, your focus really has been on all things urologic oncology, but you have a lab and you really practice quite a lot of bladder cancer management. I'm just wondering if you could talk to us a little bit about how you think about Cysview® and blue light cystoscopy, choosing patients that might maximally benefit from that kind of technology.
Joshua Meeks: Yeah, so gosh, in May of 2020 I think the biggest challenges that we deal with for patients is a risk-benefit for them to come into the hospital for an endoscopic resection. And for most patients, when we have that discussion with them, they say, "Well, how do we know we're not going to be exposed to COVID-19 or exposed to a virus or put at risk?" Because many of the patients we have, it's rare, as you know, that there's anyone without a medical comorbidity. Many of the patients we manage, the average age is in the late 60s, many have had smoking exposure. Many of them have a number of other medical comorbidities that put them at risk for some serious consequences if they are symptomatic from the virus.
So for them the first question, even when we talk about surgery is, is that safe? And I think at a hospital obviously that's safe. But I think the point where that drives into the blue light to me is that I feel like that patient's gone through an awful lot to make the decision to come to the hospital and have a procedure. So for my part, the best that I can do for them is to give them the very best surgery we can. And that usually involves not only looking with white light but blue light as well. Because every analysis of Cysview® has suggested that when you use blue light cystoscopy you see more lesions. Not every one of those is going to necessarily be cancer, but you do a better job with your surgery.
So I think for the person that is willing to come into the hospital, that is willing to do an operation, willing to do a procedure, our goal is to really do the best operation we can for them and to provide them the best quality of care so that that's hopefully the last one of these that they need. Because I wouldn't say that before bringing someone into the hospital is something that we would do without thinking. We always want to do the best job we can. But in these times where, to schedule surgery, it's not easy for us. There are hospitals reopening and it's opening at a time that is a somewhat titrated rate, where there's a lot of patients that need procedures. So every minute I'm in the operating room, someone else can't be.
And so that's a resource for our hospital, for the rest of our patients that we take care of, but also for that patient who's willing to undergo an operation. So we want to do the very best job we can. And that's where I feel that this plays a major role, that by seeing that extra tumor with a blue light that I wouldn't see with white light, that's one less recurrence that we need to manage. And so I really feel that no matter what we do, that's a better way to do that and that we can provide a better quality of care to our patients when we use that. And that's really where it fits in in this relatively tight resource environment as everything is opening back up.
Alicia Morgans: So I think that is completely in line with what I was thinking. And ensuring that you're truly seeing what's actually there and not missing it because you don't have that technology I think is critical, as you said when we're trying to maximize the efficiency and effectiveness of our procedures in a setting where we may not have as many ORs as we would like to have and everybody is stretched a little bit thin. One of the things that has been driven home by some of the guidance around caring for non-muscle invasive bladder cancer is that it's really critically important to ensure that you understand if your patient really has a lower risk non-muscle invasive disease or a high-risk non-muscle invasive disease, and certainly if that patient's developing muscle-invasive disease, that's going to be important to sort out. And do you feel like Cysview® and blue light can help with that?
Joshua Meeks: Yeah, I think in general, so generally there are two groups of tumors that we see. So we see papillary tumors, and then we see flat lesions or carcinoma in situ. Papillary tumors we tend to see a little ... I would say I still think there's a number of these small tumors that you still see better with blue light, and you can see the edges of these better. But certainly, for the flat tumors, there's a bit of a shadow or an area around the tumor that is a carcinoma in situ lesion. And so there's a lot of debate in our field about, what's the best patient to treat with this and is surgical resection part of how we treat cancer? I think there's a lot of shades of gray here where there are patients that you can see carcinoma in situ, and while we think that that's a field effect, there's certainly a role for surgery resecting them.
There's many patients that, with a good resection, you can reset the clock on their carcinoma in situ. And even though it is a field effect and it's unlikely that you've removed all of it, I personally believe you give them a running start to getting a better response to intravesical therapy. It's also a major disease, that if you can resect their cancer, that that puts them potentially in a better risk group. So I do think you compare that with better outcomes clinically. So that's part of the reason how I use it. So when I think about patients, it's relatively few people that I think wouldn't benefit from the Cysview® blue light. Because even people who come in with a primary tumor that's a solitary tumor that I've seen in the office that's ever had a resection, there's often tumors around there that you haven't seen.
And so that's an important resection. And honestly, having no other tumors is actually very prognostic. I think there's many of us who think that if you don't see it with blue light, you don't see with white light, it's very unlikely that they'll have a multifocal disease in the bladder because that entity doesn't seem to occur. So I think, again, that there's benefit in early-stage papillary disease, there's certainly benefit in patients who have carcinoma in situ. By all means, we know that probably the biggest indication for blue light cystoscopy is patients who have a positive cytology but a negative endoscopic evaluation. Because those are people who have CIS somewhere but you just need to find it. And again, that's where many people have used it before.
But I honestly tend to use it in all my patients with bladder cancer, for re-TURs, for people who have a new tumor, because again, the better job I can do staging them and removing all their tumor endoscopically, the better discussion I can have with somebody. Because that data, both pathologic as well as what it looks like, we really use to inform what we're going to do from there.
Alicia Morgans: I think that's really important. Because as you were saying, if you can't collect adequate data, and if you're going to the OR you better collect adequate data. It's really hard to then stage that patient correctly, anticipate their prognosis, and correctly pair them with treatment. And this is a question mostly because I'm a medical oncologist, so I don't do these procedures. But one thing that I've heard us talk about in tumor board, and sometimes just when speaking with other urologists, is that it's really important too to have the flexibility when you're doing that scope to make sure you can see the entire bladder. So back by the bladder neck and through the entire bladder. Is this something that the Cysview® technology allows you to do, that you can angle and get in those areas that you need to really see things properly?
Joshua Meeks: Well, there is a bit of scattering for normal tissue at the bladder neck. So probably the value of Cysview® at the bladder neck is probably a little bit less clear. Because you're seeing the edges of the bladder, and you can get some reflection that looks like it's a little suspicious. But when you look at it a different way you don't really see that. So I would say that the areas around the bladder, the ureter orifices, the bladder neck, they can be a little challenging. Again, the more people do them, the more you see that, and the more you can say, "Well, that's tangential. I don't think that that's real." But I'll tell you, you'd be very surprised how many things that you see that ended up coming back with biopsies of dysplasia that are really subtle.
And again, I think that leads to, that's almost ahead of the curve for our pathologists because we're providing them with biopsies that they haven't always seen before. And so we're kind of, I wouldn't say forcing them to make calls on that, but I certainly believe that if they're having to say, "That's dysplasia, that's cancer, that's going to be tumor at some point in the near future, and we're trying to treat that as fast as we can." I think that may be what we're going to eventually be doing with flexible blue light once that's more ubiquitous in the clinical setting.
Alicia Morgans: Great. And just to continue on with our conversation about non-muscle invasive bladder cancer, you've done a lot of work with BCG unresponsive non-muscle invasive bladder cancer. And we recently had approval from the FDA for pembrolizumab to treat that population. So these patients who are ineligible to or refuse to undergo cystectomy, and that can't be uncommon, that happens, but who do have BCG unresponsive non-muscle invasive disease. Have you encountered this patient population? Have you started using pembrolizumab in that setting?
Joshua Meeks: Absolutely. I really think that prior to two years ago we really had very little for them. And that's where you had a lot of single-arm Phase III trials where you're just trying to see, do you get a biologic response that's better than valrubicin, which has about a 10% to 12% response over that first year? And so pembrolizumab, the strength is the durability, but also the strength of that is the lack of progression. That's ultimately what kills the patient, is not a positive cytology, it's progression to disease outside the bladder. And that early KEYNOTE-057 data suggests that there's a durable response there. So I really look forward to seeing what the long-term data shows. I think that when we talk to patients who come in and aren't responsive to BCG, we now have a bunch of options for them.
So with pembrolizumab being Q6 now as a possibility, and living in a major metropolitan area, that's fewer trips they have to take down. That's another opportunity for them to receive therapy here but still live in the suburbs and be able to be cared for. So it's great to have that option for folks, and we're pretty selective about who that's right for because of course there's that toxicity balance that we have to have a discussion with, that you can avoid somewhat with intravesical therapy. But I'll tell you, there's a lot of folks who are very interested and they take us up on that offer. And again, where that plays into how we evaluate patients is that you don't know they're refractory unless you've done the evaluation and you really see that carcinoma in situ. So again, better staging leads to moving people along when they really have recurred.
Alicia Morgans: Agreed. And just to reiterate that, it was only in the last couple of weeks that we heard from the FDA that there was a reanalysis. It's not a clinical trial, a prospective clinical trial to determine this, but modeling and reanalysis, looking at some of those dependent data, that the FDA has said that we can use 400 milligrams IV every six weeks of pembrolizumab instead of the 200 Q3 weeks, which we had been using previously. And so this is something that is certainly rolling out in medical oncology and urology clinics widely, I think, at this point.
Joshua Meeks: Yeah, again, a bunch of options for folks. If we're looking at cystectomy as a gold standard, having options before that gives us a chance to figure out what people will potentially respond to. It's not muscle-invasive disease, you likely have a window of opportunity to say, what is their disease going to respond to? I really talk to folks about finding the right key for the keyhole of the disease that we're treating. And we have a bunch of therapies, so how do we figure that out the fastest to try and treat their cancer? Obviously the concern is progression. So this gives us an opportunity to treat them, and I think it may or may not be the first one we go to, but I think it's great to have that for folks.
Alicia Morgans: I agree. Well, thank you so much for reviewing your approach to cystoscopy using blue light and Cysview®, and certainly reviewing this new approval of pembrolizumab in the BCG unresponsive high-risk non-muscle invasive patient population who really can't undergo cystectomy or are electing not to undergo cystectomy. I think this is all really important and evolving so quickly that it's great to hear from someone who's really on the cutting edge how to best think through these things. Thank you so much for your time.
Joshua Meeks: Thanks, Alicia.