Ashish Kamat: Gives me great pleasure to welcome Josh Meeks here today, Assistant Professor at Northwestern and an expert, already, in the field of bladder cancer. So Josh, thank you for taking the time in being here today.

Joshua Meeks: Thanks, Ashish. It's my pleasure.

Ashish Kamat: Now, you're obviously doing a lot of stuff at GU ASCO this year, but one of the things that caught our eye was you are charged to come up and inform the field as to the top three or four research papers that have influenced your practice in the last year. So, I thought maybe you could share that with our audience as well.

Joshua Meeks: Sure. I think it's a very big challenge to try and understand what is the best, most impactful in our field. My thought really starts with the real concept of checkpoint therapy. And I think that really, as you know with the patients you take care of, there are clearly people that we care for now that wouldn't be alive if they didn't have the chance to get that therapy.

There's a reason why it was the Nobel prize. I think that looking from the metastatic setting all the way to muscle-invasive, non-muscle invasive now, that's absolutely changing how we care for our patients and it's not probably going to be that every single tumor is going to respond to it, but certainly, it's another tool, it's another group of patients that we can treat that really is changing how we care for patients. So, I would say to me, that that's probably number one.

I mean, what's been your experience with what you've seen? I imagine it's very similar.

Ashish Kamat: Absolutely. I agree with you. I think the IOs and of course, Jim Allison being at Anderson, we're a little bit biased, but even without that, it's really changed the whole playing field when it comes to patients and people who didn't have an option before now, now have an option.

But I want to ask you a question there because you have had an interest in immunotherapy for bladder cancer, BCG, interferon, et cetera. What's your view in the IO approval in the BCG unresponsive space and where it could possibly find a home in an earlier phase of a disease?

Joshua Meeks: So, I think the big thing that I think of is, when you talk to a patient at this point, these patients are very heterogeneous. There are some who have a good renal function, there's some have good performance status. And in them, they have now options to consider. Whereas there are many patients who don't have that and they like the fact that it's an every three-week installation. They like the fact that it has systemic delivery. So, for example, in a T1 who has a recurrence very quickly after BCG, and you're not worrying about CIS and cells being positive, you're worried about progression. And so, for them, I think it really makes a lot of sense.

So, it's something that I talk to every patient about, but it's going to be very specific. Again, I think if you're thinking about organ preservation, more of the solitary kidney with recurrent CIS in that kidney, I mean you're thinking about nephrectomy and dialysis versus this. The real question though is how do we measure when we go on to another drug because we don't have the same criteria. So, it's an exciting time, but I think that it definitely is a new tool that we have for patients.

Ashish Kamat: Absolutely. That's a great point. And we could talk forever on that topic, but you have three others you want to talk about.

Joshua Meeks: Yes. Number two, TCGA. So, The Cancer Genome Atlas published in 2014, the update in 2017. When I think about how I think about patients and their tumors, that's the blueprint, right? So, every patient that we see, we're thinking, "What are the alterations? How much mutation burden do they have?" I mean, the thought that tumors that have a higher mutation burden have better survival, a lot of that is probably the immune response that they have. Not to mention all the targeted therapies that are present now and coming down the road.

Just looking at FGF receptor 3 now, but there's going to be more in the future. I think once again, that's the blueprint for how we treat these tumors and who we give which therapies. So, I try and get my residents to, I tell them, "Print it out. Put it in your pocket. Keep taking a look at that." Because the nice thing about that is we paid for that. Our tax dollars went to that. It's free for everyone. You can go pull that data, you can look at that. If you have an idea, you can get all that preliminary information and it's available to everyone. So, the TCGA and really the mapping of our cancer, I think that's a critical piece of information.

Ashish Kamat: Yeah. And I liked the way you framed that. It's the blueprint on which we can base a lot of targeted therapies and understanding of the biology of the disease. Let me ask you a question that I often get, but I want your response. Because I will often get critics of TCGA or gene expression profiling coming and saying, "Well, it's not going to pan out. It's just a research tool. You guys are just wasting money doing this. It's all going to be about IFC and clinical stage." What would you have as your response to that?

Joshua Meeks: Well, that's our challenge. That's something we need to do a better job with. I mean, I agree that it's moving from, once again, the blueprint, which is frozen tissue at institutions that do a high volume of surgery. And it was meticulously controlled. Well, now we can translate that to paraffin, which we have available at our institutions. And really it's on our shoulders as the physician-scientist in this field to translate that to assays that can be employed for our patients. So, I agree that for now it's in a different space and it needs to be to apply to individual patients.

But the two things that need to happen are, the science needs to get better, we need to do a better job of applying that. And the second part is we need better trials to put that into place. So, when we're doing these clinical trials, we need to be asking who's the responders, who are not the responders? Are there people that are outliers that we should be looking at. So, I definitely see that that's a challenge, but I really think that that's our job to take that that's been produced and now put it into practice.

Ashish Kamat: Right. I mean, that should be a critical part of any clinical trial that's been done, and it is. I mean, nowadays all the trials moving forward always have that as part of it.

You've also done a good amount of work when it comes to actually understanding the nuances of the RNA, DNA. Obviously, again, that could be a whole other topic, but just for our viewers really quick, in the hierarchy of information versus costs versus the pain involved, what would you rank those?

Joshua Meeks: Well, I think, to start with the DNA is probably going to have more targets and it's going to tell you, similar to lung cancer, what are the alterations, right. But then going forward, the plasticity of RNA is going to be very helpful as far as characterizing these tumors. I mean, again, I'm an advocate of subtyping because I don't think we can describe these alterations like lung cancer where you have individual genes. We have few drivers, so few oncogenes and we have many more tumors that we need to divide the basket up, to say how do we best treat those.

So, I think right now if I had one test, it would probably be TMB plus alterations. But I think going forward there's going to be a lot of thought put into RNA. And the questions are going to be, inter-tumor heterogeneity. So, if you biopsy one part of the tumor versus another, are those the same? But again, those are assays that we need to develop. And I think there's going to be a lot of interest in that in the future.

Ashish Kamat: All right, great. And the third thing?

Joshua Meeks: So, I think the two randomized trials comparing open to robot cystectomy. And again, that is the sort of penultimate operation that we perform as urologists, but we've had two randomized trials saying that whether you do it open or you do it robotically if you do a good job, the outcomes are the same. Right, there are differences. There's length of stay differences, there's complication differences between the two. But unlike many fields, not just in urology, but all across cancer surgery, people haven't done these randomized trials. The technology has moved faster than the surgery can. For example, prostate cancer, you couldn't really pull it back and say, "What's better?" But for us in bladder cancer, we've done those trials and there's no difference, which just means that if you do a good job, you can do either one. And when I meet with patients and you have a discussion, they may have one idea. You can say, "Well I think your case may be better done this way." It just means that the technology doesn't trump the surgeon and the operation and the cancer.

So, I really give the groups, both the RAZOR group as well as Memorial a lot of credit for doing these randomized trials to look at what's the best and safest for the patients.

Ashish Kamat: I think you're making a good point there because clearly RAZOR and then Bernie Bochner at Memorial and then the European study that's going to be right out pretty soon. I suspect that those will finally, hopefully, put to rest this endless debate as to whether you should do it open or robotic because we can spend our energy in much more important questions without worrying about how you do it.

In your program though, if you choose between open or robotic or if you do both, how do you incorporate ERAS® into one or the other or do you think it's necessary or trumps, the technique of surgery?

Joshua Meeks: No, I think that's the point. If you do the right surgery and I benefit from having colleagues that do only open and I'll do open or robotic and we look at our outcomes. Really the ERAS® approach is what really is one of the bigger differences for patients. So, everybody in our institution gets ERAS® as a quality measure and then the surgery can be open or robotic. And again, I worry more about those patients that don't get an operation or don't get definitive therapy, whether that be chemoradiotherapy, but I think really just focusing on getting the treatments probably the most important. They all get ERAS®.

Ashish Kamat: All right. And then ERAS® is the great leveler, right? I mean, it levels the playing field and everything else is on top of that. This has been great. Any closing thoughts?

Joshua Meeks: I would add one more and that would be enhanced cystoscopy. And really those papers aren't just one year or two ago and we're moving from rigid cystoscopy to flexible cystoscopy. But, as you know, when you look at a patient's bladder and it's normal and then you flip over to that enhanced cystoscopy and you see lesions, I mean that changes both how you manage that patient as well as the therapies they're going to get and everything else.

Again, I've gone from doing some to essentially employing that for almost every one of our patients because it makes you do a better surgery and again, if we do our part as surgeons and do a better job with the resection, I think that's only going to add to the intravesical therapies we're giving. So, I would say the fourth would be an enhanced cystoscopy.

Ashish Kamat: Yep. I'm totally with you there. I mean that's out of my soapbox. I think the initial resection diagnosis, the QRBT has been downplayed a bit too much in the US and overseas and a good TURBT coupled with enhanced cystoscopy is key. One of the challenges in the US is the fact that the Blue Light agent is linked to just one manufacturer of the scope. But there are other companies coming in developing cameras that are agnostic to the actual resectoscope. And I think that would be another huge advantage for the field because as you probably know, there's a lot of centers in the US that can't invest in a brand new tower that goes with one manufacturer. But if they have a camera to just hook onto what they already have, that'd be great. And that is actually in front of the FDA and hopefully, we'll have it available for our community.

Joshua Meeks: That'll be great. Again, from an educational perspective, working with other surgeons, that even with surgeries that I do, just flipping over and seeing that there's a rim around a tumor that you thought you got, and then there are other targets. So, I think that's going to help. My guess is that that's going to be a long curve as far as recurrence, but I think that's going to put into that.

Ashish Kamat: Great. Well, thank you again for taking the time from a busy GU ASCO and I really enjoyed this.

Joshua Meeks: Thanks again, man.