Successful Bladder Cancer Programs: What Should You Be Offering Your Patients Today and Tomorrow? "Presentation" - Daniel Saltzstein, Jonathan Henderson & Jay Krishnan

November 14, 2023

Tom Jayram hosts a panel of experts to discuss advancements in bladder cancer treatment, emphasizing personalized therapies, clinical trials, and the importance of a comprehensive approach. They highlight the role of nephron-sparing techniques and new tests in improving traditional diagnostic methods.


Tom Jayram, MD, Urology Associates P.C, Nashville, TN

Daniel Saltzstein, MD, Urology San Antonio, San Antonio, TX

Jonathan Henderson, MD, Arkansas Urology, Little Rock, AR

Jay Krishnan, MD, New Jersey Urology, NJ

Read the Full Video Transcript

Jason Hafron: Our first session, "Successful Bladder Cancer Programs: What Should You Be Offering Your Patients?" I ask the moderators and the panels to come up and take their seats. This session will be moderated by Dr. Tom Jayram.

Dr. Jayram is a urologic oncologist and the director of the Advanced Therapeutic Center in Nashville. Tom is a clinical associate professor of urology at Vanderbilt, and has developed one of the first urology-specific comprehensive immuno-oncology programs where patients can receive novel personalized therapies or trials, which will significantly impact their life. Tom also runs one of the largest bladder cancer research programs in the country.

On his panel is Dr. Jayram Krishnan. Dr. Krishnan is a member of Summit Health Urology, and his practice focuses primarily on urological oncology. We have Dr. Dan Saltzstein who is the Medical Director of Research and the Director of Vance Therapeutic Clinic at Urology San Antonio. Dan has been the principal investigator of over 150 clinical trials, and has authored numerous papers over the last 30 years.

Last but not least is Dr. Jonathan Henderson from Arkansas Urology in Little Rock, Arkansas. Dr. Henderson is an expert in urologic oncology and is the immediate past president of LUGPA, and has been on the LUGPA board since 2011. Here we go, Tom. Thank you.

Tom Jayram:
Awesome. Well, thanks for coming, Dr. Hafron and Dr. Brown. Thank you for asking us to talk about this and putting us first. That's really important. Bladder cancer is the most dangerous disease that we as urologists treat, and it's very exciting to see the progress that has been made over the last few years by big groups consolidating their resources, and really trying to improve the structure of our programs, improve some of the gaps that we had previously encountered in bladder cancer care.

Now, we're in a position where all groups know the importance of what's happening, and all of the new therapies and modalities that are coming into this space, we all know about, but the goal for this session is to talk really to members of large groups and people who do a lot of bladder cancer and see, how are things moving? What does the real world look like? What's happening on the front lines with bladder cancer? And how can we get better? And really, what does good look like in this space?

We'll go over a few slides, but I'm going to kick this out to our panelists, and really everyone and anyone feel free to chime in, and if you have any questions or comments.

I put this slide up. I think it resonates with this group, one of the real modern success stories of big community urology is what we've done in prostate cancer, how we've integrated advanced prostate cancer programs and centers of excellence into our groups, and really, it's materialized into very successful outcomes for our patients.

This resonates with me, as someone who was interested in building a bladder cancer program. You can see here, a lot of these things are kind of interchangeable now with what's happening with bladder cancer. The consolidation and regionalization of surgical therapy, I think, is very important.

Most of our groups have one or two or three high-volume providers that are doing cystectomies. Some practices are even regionalizing their TURBTs, but also, there are new therapies: immuno-oncology drugs, targeted agents are starting to come in. We are having to respond to this, and say, "Well, are we going to do this? How are we going to hand this off to our colleagues? Who are we going to hand this off to?" It's something that's starting a new dialogue in a lot of our groups.

Cancer trials and clinical trials is a passion of mine, and many groups in this room are involved in clinical trials, but really, the busiest space in urologic oncology is now bladder cancer and BCG unresponsive disease, as well as BCG naïve disease, so there is really an opportunity here for groups that are interested in trials or groups that are looking to expand their footprint to try and offer their patients something a little bit different and improve the menu of options.

This second slide really just mirrors the first slide. I think the goal here is to improve outcomes in an otherwise very dangerous disease, and that's really what we're starting to see. We're starting to see groups become better at rationing BCG; we're starting to see groups be better in regionalizing surgery; we're starting to see groups administer their own systemic therapy so that patients can have a little bit more of an easy and predictable experience in the process.

I'll kick this question out to the panel. What do you guys see in terms of similarities between what's happened in your practices with advanced prostate cancer and bladder? And how do you see an overlap with these?

Jay Krishnan:
I can go first. Thank you. First of all, thank you, Tom, for inviting me to this panel. Thank you, Gordon and Jason, for putting this together. I think the biggest thing is immuno-oncology, and I think we've seen that already in advanced prostate cancer. We've already done that in our practices.

We never really thought about it for bladder cancer, and I think that's where we have a huge opportunity to embrace immuno-oncology (IO) therapy within our groups, and take that back from medical oncology and keep that within our own groups. I think that's what I've seen. Do you guys agree?

Daniel Saltzstein: Yeah. Again, in similarity to prostate cancer, there was a bunch of new diagnostic tests, then we had some drugs that were very effective in treating patients, and we're starting to see the same thing in bladder cancer: better imaging modalities, better biomarkers, clinical trial opportunities where we can move drugs into earlier stages of disease, so definitely following a similar pathway.

Jonathan Henderson: Tom, I think it's been about six years since somebody, probably Neil, first said, "Hey guys, this is the next frontier. Time to get on board." And much like with prostate cancer, when our group said, "Wait, we're not used to giving prednisone with ABI. We're not used to infusing it." There was so much pushback because it was outside of our comfort zone, that here we are, six years later, and very few of us have really gone into that next phase, as I think we should have.

We're starting to see more uptake of infusions and systemic therapies, but the disingenuity of it all is, it doesn't take many BCG treatments before you get somebody BCG septic to realize that we've been giving systemic therapy all along.

Tom Jayram: Absolutely, absolutely. Urologists were the first really to give immunotherapy for bladder cancer. What's interesting is, on our pre-call for this session, one common thing came out, and it's funny, with all these new things coming out and imaging agents and drugs and trials, IO therapies, one thing we all agreed on should be really highlighted in this talk: bladder cancer is fundamentally still a surgical disease, and really the most impactful thing we can do for a patient is a good transurethral resection.

It was just a really common thing that everyone said. We can't lose the big picture here. Yes, there's a lot of options. There's a lot of things we can put in bladders these days, but really, on two levels, TURBT, as we all know, is paramount in optimizing outcomes, especially for papillary disease. Risk stratification is something that notoriously we are bad at, but doing a good TURBT helps.

Restaging TURBTs. Historically, the compliance to doing a restaging or a repeat TURBT for high-grade disease is quite low, but there is immense value in doing that for patients. And then even if patients don't choose to go towards a radical cystectomy, or opt for something else, we know that keeping their bladders as clean as possible before they get radiation or before they get other therapies is really good for optimizing outcomes.

And then I think radical cystectomy, 20 years ago, I would say there would be a small number of community urologists who were doing a lot of radical cystectomies. I don't know many big groups or many groups here that are sending away their radical cystectomies at this point. Most of our groups have urologic oncologists; they're doing these surgeries, and we know it's volume-based outcomes. People who do a lot get good results.

Doing things like centralizing postoperative pathways appropriately, discussing when and when not to get chemotherapy, these are things that urologic oncologists do well, have great training in, they know the data, so centralizing care for those patients is really important.

Any comments from the panel? I know this was something we talked about on our call, and people were quite passionate about, about the importance of good surgery for these patients.

Daniel Saltzstein: Yeah. In San Antonio, we realized the importance, whether it's for trimodal therapy, whether it's how they're going to respond as a recurrent, as a progressive, when they get their immunotherapy and things like that. We actively pursued getting a fellowship-trained urologic oncologist. We centralized our care. We brought all BCG into one central station.

We could monitor how they were progressing on BCG and created what we would call a bladder cancer champion, somebody that was going to be the disease state champion to monitor when they really needed a cystectomy, versus leaving it to 25 people in the group to make that decision.

Tom Jayram: Any comments?

Jay Krishnan: Yeah. One thing, Tom, I would say about resection. I hammer this with the residents all the time. The best resection happens with you, and I'm not sure the residents understand that until they become the chiefs, or even get into practice, but that's the paramount of diagnosing the disease: finding those high-risk patients early, identifying the CIS component immediately.

I try to hammer it home with the residents right away. You got to really do the best resection possible for every patient that comes through the door.

Jonathan Henderson: Yeah, I'd echo that. And I'd say you have to do re-resections regularly.

Jay Krishnan: Absolutely.

Jonathan Henderson: And I don't make any apology when a patient gets sent to me from outside, and I say, "I need to take you to the OR myself. No disrespect to your referring doc, but I've got to see what's going on."

Tom Jayram: Let's pop out a little bit into what's new, what's happening in diagnostics. Historically, what we've all done when we've monitored patients is a cystoscopy and a cytology. We've all heard that and we've all used that as observation on surveillance patients, and potentially even patients who have new high-risk features: microhematuria, gross hematuria.

The world of biomarkers is changing. There's not any great option out there. We all know the limitations of urinary cytology, but there are some new things that are coming out. I would ask the group, and we'll talk about enhanced cystoscopy in a second, but from a biomarker standpoint, there are a couple of different things.

The way I look at it is that there are cytopathology markers, which are markers that you look at under the microscope that are similar to cytology that are maybe adding some value; and then there are sequencing types of markers, where you're sending urines out and you're getting some results back.

What do you guys think is where we're at today? What does good look like from a biomarker standpoint? Are you using markers all the time? How do you feel about incorporating those into your management?

Daniel Saltzstein: On clinical trials, we're definitely using the biomarkers, usually cytology, and then following up with a Reflex, UroVysion, or FISH. There was a point in time where patients were challenged to get into the office, and we were always looking for that Holy Grail to maybe avoid a cystoscopy. I don't know if there's a biomarker out there at this point in time that can truly do that.

Again, as we get started in more of the advanced bladder cancer trials, FGFR and PD-L1 status are important, but it's not ready for prime time yet, as far as how we manage a patient going forward.

Jay Krishnan: Yeah, I'd echo that completely. Cytology and FISH have been the mainstays for us.

Jonathan Henderson: Yeah, I think there's been a decline in cytology utilization, and I'm not sure that that's all good, because I don't know that we have an adequate replacement, but that's just my sense.

Tom Jayram: Yeah, I would definitely agree with all that. And I would say, to Dan's point, I think the important thing is that this stuff is coming. Our experience with genetic testing and tumor testing for prostate cancer is becoming pretty robust. And again, I think it's something we can lean on, because that's going to start coming into bladder cancer a little bit more, but likely not ready for prime time yet.

Jonathan Henderson: Tom, can I interrupt you?

Tom Jayram: Yeah.

Jonathan Henderson: Yeah. Circulating tumor DNA, I guess B and CME, we're not supposed to use names.

Tom Jayram: Yes.

Jonathan Henderson: Do you use that? And I'd be interested to see how many people in the audience are using that.

Tom Jayram: Yeah. Is anyone using ctDNA in bladder cancer? I think it still falls under the umbrella of a couple of people. It falls under the umbrella of very interesting. There's a lot of data, especially in other tumor types, a little bit in bladder. I do think there now is a movement, now that we have options in the adjuvant space, so you can give patients IO post-cystectomy if they have active disease or if they have high-risk disease.

I do think that's probably the space that makes most sense, so you test someone post-cystectomy, and if they have circulating tumor DNA, they would likely be a good candidate for IO. The situation is a little bit more complicated than that, but that's probably the space that's being used the most.

I do have some patients, not a lot, but I have some patients who, they're frail, they're post-cystectomy. I don't want to just treat them blanket with IO. I've had a couple of patients that if they've come back with high circulating tumor DNA, I'd say that it makes a little bit more sense.

Jonathan Henderson: Yeah. I've also seen a pretty big uptick in bladder sparing, and it seems like there'd be a good utilization there.

Tom Jayram: Yeah, absolutely. I think in patients who have trimodal therapy, chemo, radiation, this could be a marker that could basically be like an ultrasensitive PSA, where you can potentially use it every time they come into the office along with a cysto or cytology, or maybe it'll help modify how often you're doing a cysto on those patients.

I've heard the ultra-sensitive PSA concept mentioned before. I would caution people, though, that we're still a long way from that, but that's the goal, is to try and make something like that. Let me go back one.

Enhanced cystoscopic techniques are now part of the NCCN guidelines, blue light and narrow band imaging, and I would say that this is not something that's still not ready for prime time. The data supports it. How many people out there have access, either in their hospital or in their office, to some sort of enhanced cystoscopic technique?

Daniel Saltzstein: Are we supposed to raise our hands?

Tom Jayram: Maybe about half, so it's still not that prevalent, or as prevalent as I would've thought. What are the panel's thoughts on enhanced cysto? I think where we're moving is that in order to better stage and understand our patients, hopefully we get a better biomarker. Hopefully we start doing better. What are your guys' thoughts?

Daniel Saltzstein: Again, I think it helps you do a better TUR, which is what we talked about earlier. I think it helps you diagnose CIS, which is important, especially in the clinical trial realm. There's some logistical issues in coordinating the patient and how they come into the office versus a routine cysto. And then, again, there's now some issues financially with their sun setting, the maintenance of some of the equipment, so you've got to put all that together to decide on how you're going to utilize it in your group.

Tom Jayram: Okay. And then imaging, I think it's important also to mention imaging. A lot of us are thinking about or moving towards potentially bringing PET scanning in-house or into our facilities because of PSMA, and a change that has made for our patients.

I think it's important to realize that FDG PET is a very, very good staging option for patients with bladder cancer. There's going to be a renal cell carcinoma-specific tracer that probably will be approved in the next year or two. And certainly not for every patient or not every patient needs it, but in bladder cancer, you have a high incidence of patients that can't get contrast, that potentially it's a little bit harder to stage them with an infused CT, so to me, utilizing PET in that group makes sense.

And then MRI, there's a lot of interest in whether we can stage patients' cancer with MRI. You may have heard of the VI-RAD scale, similar to the PI-RAD scale in prostate, where they're looking at being able to stage patients' disease by getting an MRI first. There's some thought that that could be a good adjunct or may even be better than what we could do surgically, so that's interesting and that's something that's coming.

The BCG shortage is still an issue for many groups. Show of hands, how many groups are actively dealing with the BCG shortage? Okay, so that's probably three-fourths of that. Obviously, this has forced us to change a little bit of what we do. I think it's important for the group to know that the AUA has kind of responded to the BCG shortage by giving us updated guidelines to suggest that we don't give BCG for low-grade disease and we limit BCG to one year of maintenance instead of three.

We've had discussions about this before. This is a good place to start a bladder cancer program, by trying to observe or monitor your BCG practices in your own group. I think it gives you a lot of information about what's happening. Can you guys comment at all about your experience with the BCG shortage and where you're at with that today? Anything that's been revealing in your group?

Jay Krishnan: I can say that when we first had the issues, I immediately converted to gemcitabine docetaxel, and now the data is coming out with excellent results, so I think early adoption of BCG shortage, transitioning, getting everybody up to speed in your group, transitioning, setting up a program, like you were talking about, where it's just a pathway, where a patient, if there's no BCG, they immediately go into either gemcitabine or combo gemcitabine docetaxel.

Tom Jayram: How many people can give Gem/Doce either in their office or in the hospital? How many people are doing that? Okay, a good number. That's an important point, Dr. Krishnan, is that Gem/Doce has shown outstanding data. It's a little bit tricky to give. There are some issues with giving it in your office, and potentially with the compounding, etc., but I think a lot of groups are finding a way to do it.

Daniel Saltzstein: Tom, this was definitely the trigger that got us all into the space, and it forced us to centralize, it forced us to get a navigator to help manage these patients, identify the CIS and make sure that they were getting to the right doctor at the right time, forced us to adopt Gem/Doce, things like that, or push people into clinical trials when we had the shortage, so it was kind of the thing that started the whole thing rolling.

Tom Jayram: I get this question all the time: do I need a bladder cancer navigator? Does it help? Are they going to make me any money? Are they going to make a difference for my patients? What's the answer to that question?

Daniel Saltzstein: I would say yes. It takes a while to get that bladder cancer navigator up to snuff, but absolutely. It's helped us identify a lot of patients for clinical trials, and again, get it to the bladder cancer champion person.

Jonathan Henderson: I think that champion is paramount. We've got Jay Hewlett who's here. He's sort of the bladder cancer champion, which is going to be most important in the group, is having that physician who's your champion. He's like the Monty Python Black Knight. None shall pass.

Tom Jayram: Okay. That was interesting. Okay, so BCG, unresponsive. I was chastised to say, "Make sure we include the definition," which I think is a good point, because sometimes we glance over this and say, "Well, the BCG unresponsive space is an important space, and that's where a lot of the trials and the drugs are."

But really, I think it's important to flesh it out that if you have a patient that has persistent disease, despite what we call "adequate BCG," you may have heard the five plus two rule, which basically means an induction course plus either a second maintenance or induction course.

Within CIS, they're BCG unresponsive. That really just means they're unlikely to gain further benefit from BCG. That doesn't necessarily mean that giving them more BCG is the worst thing in the world, because honestly, sometimes that's what you have and you give them another course, but it means that that group of patients is unlikely to respond.

And then again, it's important to know that patients who have high-grade T1 after induction BCG is the highest risk group, so if you scope somebody after putting six of BCG in their bladder and they still have high-grade T1, that patient probably should have a strong discussion about a radical cystectomy.

But there are really four options now in this space for BCG unresponsive disease, and we'll just go through them really quickly. Pembrolizumab, which was approved now about two and a half years ago for BCG unresponsive CIS. I think we all have had some experience either giving it or referring patients now for this.

There are some strengths. I think the strengths are is that some patients don't want further intravesical therapy. They don't want a catheter, they don't want more treatments through a catheter. But I think the data suggests that this disease is going to recur over time, about a 19% complete response rate at one year, and then you got to deal with the side effects, and we'll talk a little bit about some of the side effects at the end, and urologists are still kind of getting comfortable.

Where do you guys stand on IO in this space? Are you using it? And what are your thoughts?

Jonathan Henderson: Yeah, using it sparingly, it just hasn't gained traction, and I don't know why, other than these are patients we've historically given intravesical therapy to, and it seems like maybe a long reach to give something with the toxicities it does. I think practices like ours that have had relationships with oncology are more likely to uptake that, but I don't know if it's not a long run for a short slide.

Tom Jayram: How many groups are giving this in their centers? Our survey data shows about 20%, which I think is probably pretty accurate, of groups are giving this in-house now. Gemcitabine/docetaxel, we talked about the data is really good. There's some discussion that the trials weren't randomized and they had cherry-picked patients, but I can tell you that all the trials in the space have some problems to them, but the data's really good. Mike O'Donnell keeps publishing follow-ups to the initial data, and it really continues to be strong.

The problem is, as we've hinted on this, is it's difficult to give in your facility. It's difficult to compound it, and you need a hood, you need a specific type of equipment. How do you bill for it outside of service where you give it?

There are a lot of different ways to do it, and I would say that I give it in the hospital because it's easier for us, and then I've given them my protocol, and they send them back to me after they're done. I know some people are doing it in the office.

It is a painful day for the patient. They have to stay there for three or four hours getting both drugs, but I think the take-home message is you should be offering it somehow, because the data is really good. Dan, I know you guys are doing it in your facility.

Daniel Saltzstein: We've designated a day, and we have a hood close by, we mix the drug. Usually, they're only in the office for about an hour, hour and a half. We'd instill the first drug, take it out, put the new drug in, and then let them go home, something like that.

The issue sometimes is billing and reimbursement, but it ends up being the right thing for the patient, of course, and then it's a break-even, if not a little bit, if you figure out the administration fee, so we try to do it on a day where it's not going to affect a doctor's clinic and the flow in the clinic, that kind of thing.

Tom Jayram: I think that's an important point. We talk about the escalating cost of cancer drugs over and over again. I think it's important to note, for the bang for your buck, it's really good for the patient. Nadofaragene was recently FDA approved. It is basically interferon gene therapy that is placed in the bladder. The data is good, but as you can see, at one year, you still see, especially with CIS patients, 24% CR is somewhat comparable to what we see with Pembro.

One dose every three months. There is a little bit of toxicity, but for the most part it's intravesical, it's comfortable for urologists. It's very new. There's an early access program that some of us are utilizing, but there are still some concerns about buy and bill. It's an expensive drug, and these are things that are being worked out.

And then also, the administration of it. With an expensive drug, you worry about when is it getting delivered, what happens if a patient doesn't show up, and all of these things, so we haven't done one yet. I know there are a few people in this room that have. Any thoughts on nadofaragene and where we're going with this?

Jonathan Henderson: The way you have it shown here is perfect, because in my mind, you look at your CRs and you say, "Why would you give anything but gemcitabine/docetaxel?" But nadofaragene is an alternative, and I anticipate probably running through all of the above for that patient trying to avoid cystectomy.

Tom Jayram: And then the last thing we'll say is clinical trials. If you're interested, there's really four things that are being studied: the pretzel, which is a small device that's placed into the bladder that elutes chemotherapy or a targeted therapy; photodynamic therapy, which is basically light energy or some form of radiation therapy that's being put into the bladder; combinations with BCG and IO; and then I call them BCG alternatives: these are gene therapy drugs, things like nadofaragene that are being looked at.

But a very, very busy time for bladder cancer. There are a lot of active trials coming out, and I would say that those of us that have trials programs are probably seeing more activity in bladder than we are in prostate. I know, Dan, you're really active in trials. Any thoughts on this?

Daniel Saltzstein: Yeah, it's a really exciting time, whether it's an IL-15 super agonist that we should hear some readouts out coming forward pretty soon; the pretzel, we've been doing that for a while, and they tolerate it very well. It's easy to insert and remove. Good outcomes. Whether it's with gemcitabine or whether it's with erdafitinib, things like that. I think the clinical trial space is really exciting at this point in time.

Tom Jayram: Last couple things is we were asked, "Well, if you're going to build a bladder cancer program, where do you start?" And honestly, I kind of go back to the prostate cancer slide: I think you can utilize a lot of the same resources and the same planning that you use for your prostate cancer program.

Obviously, you need a champion provider. I think that's really important, someone that's interested in this, someone that knows the data, and someone that honestly kind of geeks out about it. I think that's what you need. This is a dangerous disease, and you need someone who is really passionate about this stuff.

And then the team, I don't know that the team has to be that elaborate, but I think that these are some features of the team that would help. I think having a navigator, we talked about. I think having navigation and data analytics now are kind of side by side a way to identify your patients.

I would argue that a navigator or having an analytics program for bladder is just as important, if not more important in bladder, because a patient that has a missed cysto or has lost a follow-up comes back in your practice, that could be very, very important for both the patient and it generates procedures and downstream revenue for the group. I always tell people that for patient per patient, it's more important to have a bladder analytics program, I think.

And there's now this big world of cancer survivorship. As someone who does, unfortunately, a lot of radical cystectomies, I can tell you, that's important. You need close relationships with ostomy nurses, with other specialties. You need nurses who are familiar with neobladders and catheterizing and those things, and a lot of our groups already have things like that.

But those are, I think, loose pieces that can somehow be put together to make a bladder cancer program. I don't know if anyone has any comments on structure and staff and what you guys have found that you've needed over time.

Jay Krishnan: I think it goes back to the navigator. I think one individual or a small group of individuals who are focusing on these patients, making sure they're following up for their appointments, making sure that they're getting on the right treatment pathway, I think that's the best investment you can make to retain these patients and give them the best care possible.

Daniel Saltzstein: Yeah, I would also add that it's very important in how you enter the data into the EMR so that it's manageable, structured data that you can track and getting everybody on the same wavelength, getting everybody to swim in lanes is very important in how you manage the data, too.

Jay Krishnan: Yeah, EPIC has helped us with that.

Tom Jayram: To close out, Gordon and Jason, I don't know why you did this to me, but you asked me to speak a little bit about immune related adverse events. This is important if you're adopting an IO program, but honestly, even if you're not, this is becoming so prevalent in bladder and kidney cancer that it's really important to understand what happens here with these drugs.

This is a new set of toxicities. It's not chemotherapy related treatments. I tell patients that it's not that it doesn't have any side effects, but it's different side effects, and they're usually milder than chemotherapy. It basically stimulates your body to generate an inflammatory response, and that inflammatory response can affect any and every organ system in your body.

This is really in the weeds from a course that we gave at the AUA about how to manage IO-tox, but basically what you need to know is the vast majority of toxicities are low grade. That's the fundamental take home message. Yes, severe things can happen. Grade three, grade four toxicities are possible and need to be monitored and managed, and you have to set a structure up where you're not telling your staff to just ignore a rash or ignore diarrhea.

But I can tell you in this group of patients, and we have quite a bit of experience infusing this, is that really high grade tox, middle of the night ER calls, that stuff just doesn't really happen. But again, we also have a monitoring and management program where patients get called every couple of weeks when they're on treatment, and we're very involved. The physicians are very involved with the toxicity.

I've been to several programs where the medical oncologist will come up here and talk about how these are the worst drugs in the world, and I think you have to base it on who you're treating. In medical oncology, they're often treating cancer patients that are heavily pre-treated. They're sick, they have a lot of sites of disease, and those patients are likely going to be less tolerant of really any treatment you give them. But in this space, where we would be giving these drugs, these patients are non-metastatic. They tend to be healthier. And honestly, I think that translates to better outcomes for patients.

I don't want to get too much in the weeds here, but from our experience, and I think several people that I've talked to, if you develop a program for monitoring and managing these side effects, and if you're involved, these patients tend to do well, but certainly, you can have high grade adverse events.

We have an oncology nurse now who does a lot of education to these patients. And again, I think a lot of it is setting expectations. But when you look at all the other crazy stuff we do to patients, with surgery and with some of these other oral drugs that we're giving, PARP inhibitors, I don't know that this is that big of a stretch, honestly. Any thoughts?

Daniel Saltzstein: Yeah. Again, what we end up doing is we educate them. They give them a card, and if they present to an emergency room, we try to, if they do have an issue, coax them to certain emergency rooms. We have a medical oncologist in our group, and they get his after hours number if there's an issue. Distributed throughout our pods, we have the Uro-GPO handout on how to manage these things. They're few and far between, but you need to have those safeties in place.

Tom Jayram: And I think, again, this slide just tells you, it's a little bit unpredictable, but most toxicity, you can find a pattern. Early side effects tend to be rash and GI, and then the odd, weird side effects, Guillain-Barré or severe rash that becomes necrotizing, that kind of stuff tends to happen later on. But you can predict and educate patients as to what to expect. The vast majority of patients within the first three months, I tell them, "Rash, diarrhea in a dry cough, those are the things that are most common. You probably will experience some degree of that."

I think we've talked about this, but really, in closing, I think documenting and developing protocols, as painful sometimes as it is, I think it's really important for something like this. This is a new initiative. If you're going to do this, you don't want to just dabble. You don't want to just say, "Oh, well, let's infuse a patient, see how it goes."

I think you should put pen to paper, make protocols, have a couple of your mid-level providers or nurses that you work with really be involved in this, and I think it ends up being the safest thing for the patients.

Jonathan Henderson: Tom, let me interrupt. I think one key to putting together a program is identify a specialist in each of those affected organ systems before you start doing this, and tell them what you're going to do, and make sure that you have them on board for that call when you say, "Look, Mr. so-and-SO, he's gotten IOs and he's got pulmonitis. Can you help me?"

Tom Jayram: Absolutely.

Jonathan Henderson: You don't want to blindside them.

Tom Jayram: Absolutely. Engage your specialist: endocrine, optho, derm. I have all of those people on speed dial in case I see a patient that has an issue. And the take home for this is the treatment for adverse events is usually steroids, which is an oral steroid taper, which, like Jonathan said before, considering some of the other drugs that we give, it really isn't that big of a reach. Once you do it a few times, I promise you'll figure it out.

Real quick, just to close, we had talked a little bit about upper tract TCC, and now we have a new option for potentially nephron sparing. I think we're all doing this, or we all have some experience with this, and there's a lot of cool data now that's coming out about using this in the bladder, as well.

I think the real world experience for urologists has been favorable now that we have the option to put it through a nephrostomy tube, and I think it's something that is good, because it adds to the toolbox of options that we have for this disease.

In conclusion, the importance of the TURBT, this is a surgical disease still, and really, that's what we can do to improve the outcomes for patients. There are new tests that we are seeing that can improve upon our old-fashioned cysto/cytology, BCG stewardship, and developing a way to ration BCG should be adopted by every group at this point, risk stratification, and really understanding who's the champion in your group, who can do this the best.

This is a dangerous disease and we should all put our egos aside when it comes to these kinds of patients. And then again, like I said, even if you're not giving IO, you should understand the side effects, because you're going to see patients that are on these drugs. And then clinical trial opportunities in this space are really prevalent now, and can be a life changer for patients who are otherwise looking at having their bladder removed. Okay, that's all we got.