Transcript of the 2023 Ask the Experts Event

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Rebecca Johnson:

Welcome to Ask the Experts. I’m Rebecca Johnson, the Director of Research for BCAN, the Bladder Cancer Advocacy Network. I’m honored to be hosting this evening’s event where our guest experts will be discussing what we know currently about bladder cancer treatment and advancements, and answering questions that many of you submitted during the registration process. We received well over 100 questions from participants, and we will do our best to capture all of the major issues and concerns raised, but we apologize in advance if we don’t get to your particular question.

We hope that you’ll remain with us until the end of the program when we announced the 2023 BCAN of Hope Award winner, as well as the recipients of BCAN’s 2023 Young Investigator and Patient-Centered Clinical Research Young Investigator awards.

BCAN was founded in 2005 by Diane Zipursky Quale and her late husband, John Quale, after they realized just how little information was available for patients with bladder cancer treatments and how little was being done to research new and better treatment options. Their goal was to build an organization that focused on improving bladder cancer patients’ lives, while also increasing attention to bladder cancer research efforts.

Today, that is exactly what BCAN aims to do. Advancing bladder cancer research is a critical part of BCAN’s mission, and we strive to do just that each year through our multiple research award programs. BCAN’s research awards focus on funding innovative science and addressing gaps in research and funding the best and brightest researchers. One way we do this is through our Young Investigator Award Program that supports early career researchers and clinicians who want to dedicate their expertise and talents to a career focused on bladder cancer.

Today’s program not only provides an opportunity to have your questions answered by bladder cancer experts, but also provides BCAN with the opportunity to showcase our Young Investigator Program as both of the experts joining us today were past recipients of this award. Over the past 10 or 11 years, BCAN has made over 30 Young Investigator awards, and tonight, we will be announcing the five recipients of the 2023 Young Investigator awards.

It is because of support from people like you that BCAN has played a transformative role in increasing the support and resources available for bladder cancer patients and in funding research to help advance treatments. BCAN’s research program exists due to generosity of our donors and people like you. So if you would like to help us continue to build and expand our research program, I encourage you to make a gift at bcan.org/researchfund. Your contribution will support individuals who are working to conduct better research, improve patient-focused care, and find new and novel approaches to diagnosing and treating bladder cancer. We thank you so much in advance for your generosity and support.

Now, it’s an honor for me to introduce our guest experts, Dr. Tracy Rose, who is in our 2017 cohort of young investigators. Dr. Rose is a medical oncologist at the University of North Carolina Lineberger Comprehensive Cancer Center. Welcome, Tracy, and thank you so much for joining us.

Dr. Tracy Rose:

Thanks, Rebecca. Glad to be here.

Rebecca Johnson:

I’m also honored to welcome Dr. Philip Abbosh, recipient of Young Investigator Award in 2018. Dr. Abbosh is a urologic oncologist at Albert Einstein Medical Center and a translational researcher at Fox Chase Cancer Center. We’re thrilled to have you here.

Dr. Philip Abbosh:

Good evening, everybody.

Rebecca Johnson:

Both Tracy and Phil are actively engaged in the BCAN community in many ways, and we’re grateful to have them here with us today. Lastly, before we get started, I want to mention that you do not need to take notes tonight during the program. This video will be available on BCAN’s website, bcan.org in just a couple of days. So with that, let’s get started.

I’d like to ask you to start with both answering a couple of questions, general questions that I’ll direct for both of you to respond to. The first, if you could share an exciting development in bladder cancer research or treatment that you feel either has the potential to or is currently impacting patient treatment outcomes and lives for the better, how would you describe that? I think, Tracy, we’ll start with you.

Dr. Tracy Rose:

Sure. So my answer comes with the medical oncology flavor, I think, because most of how I treat bladder cancer is by treating the whole body with systemic therapy. So that is the line of where did I go when I get asked such a question, but as we improve care, it’s been a really exciting few years in bladder cancer because we’ve seen lots of new drugs and new mechanisms and also moving earlier with response rates we’ve never seen before. So I think my answer to exciting recent development in research comes in the type of therapy. So historically, we’ve just used standard chemotherapy for bladder cancer, and then we had immunotherapy, and now we have this new type called antibody drug conjugates, which is basically chemotherapy attached to a protein that targets the chemo directly to the cancer or to a certain protein that cancer’s expressed.

So it’s really targeted chemotherapy, and because of that, we’re seeing some really nice response rates, but also some really exciting research opportunities and some drugs coming out that are really targeted based on the patient’s cancer and what proteins it expresses, and then we can take chemo and deliver it directly to the cancer.

So I think that that’s where the field is starting to go in terms of systemic therapy. It’s really exciting time where we’re actually probably going to start really selecting therapies and potentially even in the first line on what proteins or DNA expression we see in people’s cancers, really, really actually seeing this personalized medicine that has taken a while for us to actually get to.

I think we’re already saving lives with some of these drugs. The one that’s approved is called enfortumab vedotin, but there’s a number in the pipeline that are pretty exciting. So I think that would be my answer is for novel therapies and ways to deliver therapy better in terms of side effects and how well they work.

Rebecca Johnson:

Thank you. Just to follow up before we hear your response, Phil, Tracy, when you talk about some of these novel therapies and antibody drug conjugates, is that for all patients at any stage or for advanced patients or who specifically would those be appropriate for?

Dr. Tracy Rose:

Right now, we only have one antibody drug conjugate that’s actually FDA-approved, and it’s only approved in the metastatic or advanced disease setting, but we’ve seen already some data for enfortumab given before surgery for muscle invasive disease. As we get these therapies to be more tolerable and work better, you can imagine them moving earlier and earlier in the course of treatment, but right now, it’s for advanced disease.

Rebecca Johnson:

Okay. Thank you. Phil, same question, what would you say is an exciting development in research or treatment right now?

Dr. Philip Abbosh:

So I would I have a two-part answer to this. It piggybacks on what Tracy mentioned. So the idea of biomarkers to assign a therapy to the disease, that makes the therapy more likely to work. We are actually doing this already for patients with mutations in a gene called FGFR3, which is a really important growth-signaling kinase in bladder cancer. So my two parts are biomarkers such as FGFR3 and then FGFR3-targeted therapies. I think we use those sparingly now, but my hope and my dream is that we start using those a lot more, especially for patients maybe with upper tract cancers, cancers of the inner lining of the kidney and the ureter, and then also for some patients with either localized or metastatic bladder cancer as well.

Rebecca Johnson:

Then that ties in well to the second question I’d like to pose to you both, and you might have just touched on it in your initial response, but we’ll start with you, Phil, is, what is one area or can be multiple areas that you think is a really critical research priority for bladder cancer right now? What do we need to know more about right now?

Dr. Philip Abbosh:

So I will stick with what I know. I’m a biomarker person. So our lab is developing urine-based biomarkers for patients with bladder cancer. I think the idea of using urine to either detect residual disease after a therapy or try to figure out which drug a patient needs to get for their therapy is something we’re doing a little bit of now, but I really think we should be doing a lot more. There’s a ton of opportunity to build those kinds of research or clinical paradigms for treating patients.

We do urine, but I think there’s opportunity for blood biomarkers, tissue-based biomarkers when a patient has a biopsy, again, and those all could be used to direct the next line of therapy. Everybody always points to breast cancer as the golden child of your targeted therapy with estrogen receptor, HER2, triple negative breast cancer, BRCA mutations. Those are things where you know what the tumor’s makeup is, and the oncologist like Dr. Rose would give a therapy that’s intended to knock out a tumor that has that defect. So I guess that would be my answer. What I’m hopeful we see more of is biomarker, biomarker, biomarker.

Rebecca Johnson:

Yup. Great. Thank you. Tracy, same question, what do you think is the research priority right now?

Dr. Tracy Rose:

I think Phil is right in the biomarker answer, so I’ll just change my answer because he already took that one, but I do really think that figuring out what is the right treatment for the right patient, avoiding overtreatment in the people that don’t need all that treatment, but then also not undertreating the people that shouldn’t be on surveillance or need more aggressive therapy. We do this in pretty brute population-based ways right now. Really, the answer for how to figure out who needs what, I think, comes from the science of the tumor and the person and, obviously, we need to learn more about that.

I think what I’ll change my answer to, which goes along with it, is right now as we develop new therapies or even new techniques for therapies, whether that be surgery or whatever, we tend to do these large trials, and especially with drug companies, they like to test it and everyone approve it works on a population level so that we order it and give it to everyone, but really, that may not be the best approach from a patient-centered perspective.

Really, I think the research focus should be on designing our trials novelly so that we can really test these drugs in the patients that need them to be tested in, and then also designing our trials to really help compare therapies instead of having several single arm trial, for example, we’ll get into this I think later, but if you look at the non-muscle invasive bladder cancer space, we have a bunch of therapies that have been approved based on single-arm trials or some retrospective data, but we’ve never actually compared them.

So I think our research priority for the community is really coming up with studies that answer questions that really tell us what we should use for each patient. I think BCAN’s a great place to develop a lot of these thoughts and concepts and research priorities.

Rebecca Johnson:

Absolutely, yup. Comparative effectiveness research is key right now for some of these new therapies. I think you both touched on this in your responses that bladder cancer presents very differently in different patients. Some may have non-muscle invasive, others muscle invasive or even advanced disease where it’s metastasized to other parts of the body. We might jump back and forth between them, but I do want to start with some questions about screening and then surveillance and recurrence because we did get quite a few questions on those topics. I think, Phil, we’ll start with you, and you talked about urine already. Are there any other ways to detect bladder cancer other than through urine cytology or through cystoscopy?

Dr. Philip Abbosh:

So there are imaging tests. It’s unusual, but sometimes people have a CT scan for some unrelated reason like they had vague abdominal pain or they fell off a ladder or were in a car accident and, lo and behold, they have a tumor in their bladder or maybe in their renal pelvis and that it gets identified that way. That’s not really a screening test, that’s just found Incidentally. There are groups that are working on screening tests. I think the one that to me makes the most sense is a screening test that doesn’t just work for bladder cancer, but maybe works for multiple cancers.

So a company called Grail has something that’s a blood test that detects … I forget how many cancers, but they say that it’s sensitive to pick up a bunch of different kinds of cancers in early stages. There’s other companies that are working on stuff like that too. I don’t think right now there’s a … I’ve spoken with them about they’re interested in doing a urine-based test, but they’re not anywhere close to having something like that ready yet.

Rebecca Johnson:

Along those lines, are we close to having anything that would replace an annual cystoscopy?

Dr. Philip Abbosh:

Well, biomarkers. I think that that’s the idea. There are now, again, companies that are working on urine-based tests to maybe not completely avoid cystoscopy, but at least put it off or maybe do less cystoscopy. I know nobody wants having their camera put in a … So it’s meant to be a one-way street, but there are people that are working on biomarkers for cystoscopy avoidance.

Rebecca Johnson:

Tracy, once a patient has received a diagnosis of bladder cancer and they’re working with a urologist, should they also see an oncologist immediately, especially if they have a personal history of cancer, and why or why not?

Dr. Tracy Rose:

I think it depends on the situation. Certainly, academic urologists and most community urologists are pretty good at the localized, noninvasive or early stage bladder cancer paradigm. Some rare bladder cancers are caused by what we call germline mutations or inherited predispositions to cancer, especially upper tract cancers. We see it relatively often actually here at UNC. If you get diagnosed with an upper tract cancer, you automatically get some protein staining to look for something called Lynch syndrome. If there’s a very strong family history, certainly either meeting with a medical oncologist or even straight to a genetic counselor would be really potentially helpful.

A lot of the localized bladder cancers don’t really need a medical oncologist, at least at the beginning. Our role comes in once that cancer becomes more advanced or hits the muscle layer in the bladder, muscle invasive bladder cancer. So many patients don’t meet with a medical oncologist. Obviously. All of us are always happy to meet with anyone that has certain questions, but sometimes I think if there was a specific concern about genetic predisposition or cancer history, genetic counselors are actually pretty available these days and do this all the time as we learn more and more about the genetics of cancer. So that would be a good place to stop too.

Rebecca Johnson:

Okay. Great. We know that bladder cancer has a high rate of recurrence. Phil, first of all, why is that? Can you talk about why that happens?

Dr. Philip Abbosh:

Yeah. This is something my lab’s interested in. So there’s something called a field defect. So we think that bladder cancer, well, we know the bladder cancer is caused by smoking, although it’s not exactly cancer of the lung that’s caused by smoking. There’s a little bit of a different genetic fingerprint with tobacco-associated bladder cancers than, say, tobacco-associated lung or head and neck cancers, but what ends up happening is in those patients who smoke, the carcinogens in tobacco, inhaled tobacco, I guess byproducts, those carcinogens cause genetic alterations, mutations in all of the patient’s bladder cells, the lining of the bladder, which is called the urothelium.

So some of those mutations are cancerous and some of them are pre-cancerous. So what we think ends up happening is a tumor forms and then it’s treated, and genetic defects that were inherent in the bladder still persist in the normal-appearing bladder. So that reservoir of pre-malignant cells can grow out again into a second or a third or a fourth tumor. I think that explains it for tobacco-associated bladder cancers.

There’s probably a similar phenomenon that happens in patients who don’t smoke. There’s probably other carcinogens that are excreted that we ingest, breathe, drink, et cetera. Those get excreted in the bladder, in the urine. The carcinogens affect the bladder. There’s a field defect in the bladder as well from those carcinogens that, again, a tumor may be resected and then a second tumor grows out from that pre-malignant normal-appearing urothelium.

Rebecca Johnson:

One more for you, Phil, about recurrence and then we’ll get back to you, Tracy. I’m a patient. I had a T1 tumor 10 years ago with no recurrence. How long do I have to have cystoscopies to check on this?

Dr. Philip Abbosh:

Well, if you were my patient, I probably would’ve stopped by now if you haven’t had any recurrences in 10 years. I definitely have patients like this where … I haven’t been practicing for 10 years, but maybe seven years, but at any rate, those patients, I give them a little bit of a longer leash each time, and maybe they just come back and I say, “Have you had blood in your urine? Do we check a urine test?” I think in my opinion, it’s probably overkill at 10 years, but I think every patient and clinician have a different opinion on that at 10 years out.

So I guess I’ll just suggest to that patient to try to engage in shared decision making. I think there’s some benefit, obviously, to not having a cystoscopy every year, there’s also some risk, and it really just depends on what the patient’s and the doctor’s risk tolerance is.

Rebecca Johnson:

So that’s optimizing the treatment plan for the patient, specific to the patient. Tracy, on the opposite end of the spectrum, what about for a patient who’s in their fifth recurrence, has already tried lots of treatments including BCG, is that maybe when they might see you and what would some possible treatments be at that point?

Dr. Tracy Rose:

I think the answer to this somewhat depends on exactly how high risk, if you will, their cancer is. Is this fifth recurrence of a tiny low-grade cancer over 20 years or is this a high-grade cancer that they’ve gone through multiple things and keeps coming back? Because I think that those answers are really different. Still, if it’s non-muscle invasive bladder cancer, sometimes they don’t even need to meet with me, and urology will recommend either a cystectomy or another intravesical treatment. There is one FDA-approved systemic immunotherapy called pembrolizumab for a very certain non-muscle invasive bladder cancer after BCG if you meet all these other criteria.

So sometimes I meet with these people, and that’s actually a pretty recent … That’s only been a couple years since we’ve been seeing them on the medical oncology side. So I think it really matters exactly what kind of recurrence this is and how high is the risk of progression to a worse cancer metastatic disease, and that really informs next treatment. Certainly if it’s a high-grade or high risk and someone’s recurred several times, that’s when urology will start talking about cystectomies.

Rebecca Johnson:

On that point, I’m going to stick with you for a minute because you talked a little bit about immunotherapy, and we did get a lot of questions about that at multiple stages and types of bladder cancer. Can you provide a high level overview of immunotherapy? How does it work? How is it changing the standard of care and treatment? The loaded question, I know.

Dr. Tracy Rose:

Actually, it’s a very much evolving field and evolving definition too. You could actually consider many treatments, quote, “immunotherapy” depending on how you define it, but basically, it’s treatment that’s intended to stimulate the immune system, which then will recognize a cancer as foreign. The immune system’s job is to get rid of something in the body that’s not supposed to be there. So you get a virus or a bacteria or a cell that starts growing uncontrollably like cancer, and your immune system’s supposed to recognize it and get rid of it, and for whatever reason, bladder cancers can form and the immune system doesn’t recognize it.

So actually, BCG, which is used for localized bladder cancer put in the bladder is the first immunotherapy and was like that. So we talk about it now as this whole new category, but in fact, it’s been around for decades. The whole point of that is put this bacteria into the bladder, which then stimulates this immune response, and as the immune system reacts to the bacteria that’s there, it gets recognized, gets rid of the cancer too.

So we’ve now developed therapies through IVs and even some subcutaneous that have the same effect. The most popular ones, pembrolizumab, which I just me mentioned, but there’s a number of different ones are actually antibodies that block some of the proteins that essentially are expressed on cancer cells or immune cells that allow the cancer to hide from the immune system. So if you block that interaction, you can stimulate the immune system and all of a sudden it’ll recognize that cancer.

So it’s actually a very novel, it’s very different than standard chemotherapy because we’re using a person’s own immune system to go after a cancer. The immune system is an incredibly complex machine. So there’s a whole number of different ways, and actually, as we’re learning more about our old standard chemotherapies, we’re learning some of the way that those worked, where it’s actually breaking up things and stimulating immune response too. So as the field evolves, it’s an evolving definition too, but both BCG and some of the IV immunotherapies are really centered on the same concept.

Rebecca Johnson:

We know that it’s novel and there’s still a lot of research going on about immunotherapy, but is there a standard of care right now involving immunotherapy?

Dr. Tracy Rose:

Certainly, there is in the localized bladder cancer setting with BCG, and then certainly, there is in the advanced bladder cancer setting, both now with an FDA approval for after surgery for muscle invasive bladder cancer for certain patients with high-risk features, but also as a standard therapy for stage four metastatic patients. It’s pretty much integrated into everybody’s treatment, and many now integrated in first line treatment or, at the very least, second line.

Rebecca Johnson:

I’m sure, Phil, we received a lot of questions about BCG, and a lot of patients are familiar with the fact that there is a shortage of BCG. Can you share any latest information about that or its availability and whether the shortage is going to improve?

Dr. Philip Abbosh:

Yeah, I haven’t been able to give patients in my clinic BCG for six years or something. Crazy. Personally, I think, I’m not sure that BCGs coming back. I think there’s this hope that it’s coming back. I’ve lost hope and maybe that’s cynical or dark. I apologize if it’s pessimistic. There are conspiracy theories about whether the drug companies want to bring it back because it’s a very cheap, very effective method, and there are other methods that may be more financially lucrative for companies, some of the ones that Tracy mentioned.

So whether you subscribe to those or not, I’m not sure. Of course, the drug company would never say that, but I don’t see it changing anytime soon. I think the hope, I think the most likely hope is that there’s other strains of BCG that people are trying to develop, and maybe those other strains might be as effective or more effective and available soon, but I stopped paying attention because I think I’ve resigned to the end of BCG here.

Rebecca Johnson:

For patients that are still receiving BCG or received BCG, can you talk a little bit about some of the side effects that might accompany that treatment or what they can expect? We received questions about, is long-term tiredness or fatigue a likely side effect, and what about nausea or pain with urination?

Dr. Philip Abbosh:

The long-term effects, I’m not so sure about. I think the immediate things … When I was a resident, we were giving a lot of BCG that I was very familiar with, definitely pain during urination, burning urination. That’s called dysuria. You’re putting a bacteria into someone’s bladder. That is, you’re giving them a bladder infection. So the common side effects we would hear about when patients are getting BCG were certainly burning, urgency, frequency, “I feel like I have to go really bad. I go to the toilet and just dribbles and drops coming out and there’s nothing there.” That’s certainly common. Very unusual to have a systemic illness, whereby a fever or someone gets genuinely sick. That’s called BCGosis. That’s pretty unusual.

I would imagine you would feel rundown during the time of treatment. People probably have to wake up a lot at night to go pee, can’t go back to sleep. That happens a lot in patients who are of the age where they’re getting bladder cancer anyway, 60s, 70s, 80s. People wake up at night, and I’m sure a fitful sleep makes you fatigued, but I think if someone’s having long-term pain with urination, long-term frequency, urgency, waking up at night, if that was not present before BCG, that would be a surprise.

Rebecca Johnson:

Tracy, and either of you’re welcome to comment on this, but, Tracy, given that we are still experiencing a shortage of BCG, we know that patients may not be receiving the same course that they would had we not been in a shortage or maybe not receiving maintenance courses, what do we know about the effectiveness of BCG treatment without maintenance versus with maintenance?

Dr. Tracy Rose:

Well, there’s a long answer to this question. It’s been somewhat standard to give third dose BCG at a lot of places, as well as in some of our clinical trials because of the shortage, basically, sharing vials between patients and then cutting maintenance short. We bucket non-muscle invasive disease into low risk, intermediate risk, high risk. So trying to really save what BCG we have for the high risk patients, but there’s been studies that clearly show rate of recurrences is lowered if you give maintenance and if you give maintenance for three years for a high-risk disease compared to shorter. Then we are basically forced to give at lower doses or lower amounts.

That being said, some of the long-term outcomes in terms of survival are not that different. So the community has really tried to make thoughtful decisions about who to preserve for and how to cut back in ways that we’re not really compromising long-term outcomes. I’m happy for Phil to weigh in here, who actually gives, I guess doesn’t give BCG probably as more than I am.

Dr. Philip Abbosh:

So I think I would piggyback on Dr. Rose’s comments. So in places where they do give BCG where they still have it, Tracy’s right. The centers will try to give one-third of the regular dose and split one … What used to be one dose for one patient is now one dose for three patients. There’s plenty of data that says that’s as effective or maybe almost as effective as giving a full dose. It also probably reduces the amount of side effects that patients have.

Then the other institutions will try to preserve the amount of BCG, as Tracy alluded to, reducing the amount of maintenance BCG that’s given. The reason for that is you get more bang for your buck by giving the first six doses of BCG. In other words, you’re really changing the clinical trajectory of someone’s outcome by giving them any BCG. Then once you’ve got some BCG, the amount of benefit that a patient gets from getting maintenance round number one, maintenance round number two, maintenance round number three is a diminishing return. So the benefit after the first couple doses is incremental. So not having maintenance doses doesn’t give you as much benefit as having the first six doses. So that’s a way to give more benefit to more people without losing all of the benefit for some people, I guess, is the way, the Mr. Spock answer, the greater deal.

Rebecca Johnson:

Okay. Thank you both. I know we … Oh, I’m sorry, Tracy. Go ahead.

Dr. Tracy Rose:

I was just going to add, this is a little bit off topic, but it’s on my mind because literally right before this, I came from a meeting because our hospital is running out of carboplatin and cisplatin and methotrexate, all of which are drugs used for bladder cancer and all of which are generic and similarly don’t cost nearly as much as some of the other options we have. We’re now rationing, including in bladder cancer, at our hospital as of this week. So this is not an isolated problem to BCG, and it certainly feels like it’s getting worse in terms of supply and generic drugs. I think we’re having to have some of these same conversations about, “Okay. We’ll give cisplatin to the curative intent patients, but we can’t give carboplatin to the metastatic patients at the moment,” is where we’re at.

Rebecca Johnson:

All of this really drives the point that we need more and we need better therapies in these shortages. So Tracy, you mentioned in one of your comments that there are different buckets of non-muscle invasive disease, higher grade or lower grade. Phil, I wanted to ask you a question that we got about a specific type of non-muscle invasive bladder cancer, which is CIS, which we know is a higher grade and higher risk of recurrence that can appear like a patch or flat tumor. Can CIS be invisible and can chronic cystitis hide patches of CIS?

Dr. Philip Abbosh:

Yeah, for sure. So CIS is notoriously difficult to detect by the eye or by the cystoscopic eye. That’s why people have developed something like blue light cystoscopy, which maybe some of the audience members may be familiar with. That’s a type of cystoscopy where a chemical is instilled into the bladder about an hour before the cystoscope is put in. Then instead of using a white light or maybe in addition to using a white light, a blue light is also used and the blue light, when it shines on the CIS after it’s been marinated in that chemical, the CIS turns pink and it makes it a little easier to see, makes it stick out a little more obscure, and so you can see it better. There are certainly cases where CIS is not seen by the naked eye or by the cystoscopic eye by white light and then is visible with blue light.

The excitement about blue light cystoscopy was very high when it first came out in the early 2010, 2012, 2013 timeframe. Now that we have more experience with it, there’s a little less excitement. The long-term survival of patients with CIS in terms of their recurrent … The idea was if you were detecting more tumors, patients would have less recurrences over time. As it turns out, that’s probably not true or at least there’s some evidence anyway that it’s not true.

I think that probably goes back to this idea that I alluded to earlier about the field defect, field cancerization defect of the bladder, where the entire urothelium is just at risk for becoming malignant at any time after someone has been diagnosed with bladder cancer. So certainly, blue light helps, but how much it helps I think is maybe a little more debatable now than it was 10 years ago.

In terms of CIS being able to hide in chronic cystitis, I’d say yes, for sure. If it can hide in a seemingly normal bladder, it can surely hide in cystitis, chronic cystitis bladders. We see that in patients who have had multiple bladder tumor resections, multiple urinary tract infections. Maybe they have a catheter, things that cause inflammation in the bladder, cystitis. That can certainly mask CIS, for sure.

Rebecca Johnson:

Okay. Thank you. So we’ve talked a bit about non-muscle invasive disease and some treatments for that. I want to shift a little bit now to talk about muscle invasive disease when the tumor has grown deeper into the layers of the bladder, and we know that one option some patients might pursue or might have is bladder removal. Tracy, what’s the current thinking about patient outcomes for a patient that has chemotherapy followed by bladder removal versus bladder removal only?

Dr. Tracy Rose:

So these studies are actually now measured in decades old. The initial study is looking at whether adding chemotherapy either before or after cystectomy improves long-term outcomes. The ones that tested it after had trouble with accrual and essentially never came out to be positive, and the ones that looked before pretty consistently show the modest benefit with the addition of chemotherapy before surgery.

I usually quote patients 5% to 10% improvement where I can really flip people from not cured with surgery to cured with surgery plus chemo at the five-year mark after surgery, but the caveat to that is that this is really only chemotherapy that has a cisplatin backbone, which is a chemotherapy drug that’s not always that easy to tolerate, can cause kidney problems, and so you have to have pretty pristine kidney function to get it safely, can cause hearing problems, nerve issues.

So roughly, at least at UNC, we’ve looked at our data. Just over half of patients are actually able to get the cisplatin safely. So we can’t treat everybody with it. The risk benefit favors chemotherapy certainly before surgery for most patients if we can do it safely, but it’s also not a gigantic benefit where people can’t get chemotherapy that they’re not going to get cured with surgery because surgery also cures a lot of people in itself too. So we give it if we can. Then there’s now an approval for immunotherapy after surgery, which at the moment has delayed time to cancer coming back. We’re hoping we’ll improve survival in general, but that data we haven’t seen yet.

Rebecca Johnson:

So you mentioned that I think you said only 50% of patients are cisplatin eligible. Can you talk about what would make me eligible or not eligible?

Dr. Tracy Rose:

Yeah. I think the number goes up a little bit with time because I think we’re getting a little bit better at managing chemotherapy and a little more aggressive about trying to treat people. The most common reason that people can’t get cisplatin is kidney function. So obviously, patients with bladder cancer are at risk of having secondary kidney problems, whether their kidneys are obstructed or a lot of our patients are older and have diabetes and hypertension and have chronic kidney disease from that. So that’s the most common reason, and then people who have hearing loss or people who have baseline neuropathy from diabetes or numbness or tingling in their fingers or toes.

Then there’s various other things, heart failure. Age is not really a contraindication. Typically, if someone is safely thought to undergo cystectomy, typically, I can safely give them chemotherapy too, and sometimes I just give them a little bit gentler doses, but sometimes we take that into account with the whole picture too.

Rebecca Johnson:

Okay. Phil, on that note, is there an age when bladder removal is too dangerous to do?

Dr. Philip Abbosh:

So I talk about this sometimes with patients. There’s a chronological age, which is how many years old you are, and then there’s a physiological age, which is how old you maybe feel. I think I go less by the chronological age and more by the physiological age. So for example, and I’m going to use very extreme examples here, but let’s say we had an 80-year-old patient who was really active, maybe plays golf every day and walks nine holes or 18 holes and has few medical conditions on one hand, and then on the other hand, maybe you have a 60-year-old patient who’s a heavy smoker and they’ve had strokes and heart attacks and everything, and they both have the same stage of disease.

I might feel actually better about taking someone who’s 80 in otherwise robust physiologic age for a cystectomy as opposed to a 60-year-old patient who’s been chronically ill and maybe not in as good shape. So I don’t think I’d put a number on it, but I haven’t done very many cystectomies on people who are 80 either. So again, it’s shared decision making. I think all of it goes back to what the patient wants to put themself through.

Rebecca Johnson:

Sure. Yup. On that note, I’m sure this also varies from patient to patient and is patient-specific, but in general, can you discuss some of the challenges or side effects that a patient could expect once their bladder is removed?

Dr. Philip Abbosh:

Well, it’s a multiple organ surgery. We take out the bladder, we hook up the kidneys to a new segment of bowel. So there’s a GI portion to this. We work on lymph nodes. So the preoperative, you’re going to maybe have a cystectomy discussion as a 45-minute discussion that is really aghast, a somber thing to put people through because it’s a really big surgery. You’re going to have at least one good size incision and maybe a couple of other ones depending on the way your surgeon does it. There’s a, I don’t know, 25% to 50% chance you’re going to need a blood transfusion. There’s all kinds of complications that happen from removing organs and putting them back together in an unnatural way. So those kinds of things are things I focus on when I talk to patients about this.

In terms of the other important … Sexual dysfunction is a very important thing for patients, especially now when people are more … That’s something people care about, and not only do they care about it, but I think it’s less taboo to talk about that with their doctor now than it ever has been, sexual side effects for both males and females who are undergoing surgery.

Then I think there’s also a very psychological component to this. People have sometimes body image issues. They’re worried about having an ostomy. They’re worried about going to the beach or taking their shirt off in public. Those are all real things. Patients often don’t believe me until they go through it, but I just try to help people understand that you’ll get to a point where this becomes your new norm. Instead of going pee, you’ll just pee into a bag or if you have a neobladder or a pouch or something, it’ll become your new norm. After a while, people just forget about it, and it really does become the new norm. It’s less scary once a patient gets used to it.

Rebecca Johnson:

Tracy, for patients who this either isn’t an option to have surgery or they’re not interested in having the surgery, what is the latest information on bladder sparing protocols for muscle invasive disease?

Dr. Tracy Rose:

So as an alternative to cystectomy, we commonly use a combination of maximal tumor resection followed by chemotherapy and radiation together. We know that some patients do really well, actually, arguably comparably well to patients who have cystectomies, especially certain tumor characteristics. As Phil was talking about, if you have multiple tumors all throughout your bladder, it’s very hard to successfully radiate all of them. So potentially, cystectomy might be a better option or if the tumors were all invasive and blocking things, sometimes radiation is not a great option, but for some patients, especially those with small focal tumors, results are really comparable to surgery and you get to keep your bladder.

So a lot of patients meet with … Everybody at UNC, pretty much with muscle invasive bladder cancer, meets with surgery, radiation, and medical oncology when they first get diagnosed. We typically will give chemotherapy concurrently and patients tolerate it pretty well. There’s side effects to radiation too, but some of the issues with having a pouch long term are not there.

There’s some newer data looking at length of radiation. That’s decreased from six and a half weeks to four weeks in a lot of patients based on some data in the last couple years. So it’s not even quite a time commitment as it used to be for some patients. So really, I think it’s a good alternative for some patients. There are still the patients that we relatively strongly favor surgery for if they have certain tumor characteristics, but for patients that either can’t have surgery or for those with good favorable tumor characteristics, I think it’s a really great option.

Rebecca Johnson:

Phil, for those that do have surgery, are there standards for surveillance post radical cystectomy or is it case by case?

Dr. Philip Abbosh:

No, there’s definitely a guideline. So there’s a couple of different guidelines. I think the ones that most people use, the ones that I use certainly are called the NCCN guidelines or the National Comprehensive Cancer Network guidelines. So typically, that means surveillance for the audience really means looking for the cancer to come back. So in anyone that has a cystectomy, they’re hopefully going to have a presumably disease-free interval after their surgery, and hopefully that disease-free interval goes until they pass away from some other cause, but in a good number of patients, the cancer will come back and it will spread. It could come back in the area of the pelvis, in a lymph node, the lungs, the liver, a bone, anywhere.

So that surveillance is important because we think that if the cancer recurrence is caught earlier, getting them from the surgeon’s care to Tracy’s care, to an oncologist’s care is going to help them have a better outcome to get treatment when the tumor’s small. So the general rule of thumb is every three months for two years, then every six months for two years, and then every year thereafter is typically the way the surveillance occurs or the timing.

What surveillance consists of is typically going to be some scan, usually a CT scan, a clinical evaluation. You come see your surgeon or your medical oncologist. They talk to you about how you’re feeling, examine you, et cetera, and then lab work that’s relevant to your other medical diseases.

Rebecca Johnson:

Tracy, for patients where the cancer does spread to other parts of the body as Phil was just mentioning could occur, what’s the best treatment plan once the bladder cancer has metastasized, and does it depend on where the bladder cancer has spread too? So if it’s metastasized to the pelvic cavity versus the brain, are we looking at different treatment options?

Dr. Tracy Rose:

So in the vast majority of cases, once the cancer has spread to other places, it’s really what I consider a systemic process. What I mean with that is it’s a cancer that’s in your whole body. So occasionally, we can see one or two or three tumors that we can measure on a CAT scan, but inevitably, there’s cancer cells elsewhere too. So because of that, typically, treatment is targeted at the whole body. Typically, that has historically been through intravenous treatment.

Now, we have erdafitinib, which is actually a pill, but either way, it goes through your bloodstream and gets all the sites of disease. The brain is a very special place that actually bladder cancer very rarely goes to the brain. If it does, usually we’ll handle it with radiation, but other than that, most of the time we treat with systemic IV or pill therapy that’ll treat all the locations. Occasionally, we do use radiation in really rare crisis where it’s just one spot and it’s been a long time or even surgery, but those are pretty much the exception. The norm is to give systemic therapy, which historically had been IV chemotherapy, but now, there’s a whole bunch of different classes with immunotherapy and then erdafitinib, which is a pill-targeted therapy against those patients Phil was talking about, FGFR3-mutated patients, and then we have these antibody drug conjugates. The landscape is changing very quickly in which ones we use first and which one in combo or without, but most of the time, it’s chemo.

Rebecca Johnson:

That’s a good segue to my next question for you, Tracy, which is for patients that are receiving immunotherapy, are all immunotherapy drugs basically the same and would you ever switch among them?

Dr. Tracy Rose:

So it’s a good question in a very confusing state because all at the same time, initially, we had five different, what we call, immune checkpoint inhibitors, which are IV immunotherapies approved at the same time, all targeting either one side of a protein interaction or the other side. Actually, the FDA’s withdrawn a couple of those. So now, it’s basically very similar drugs that have all just been studied in slightly different disease states and therefore have slightly different FDA approvals.

Nivolumab we use after surgery for patients with muscle invasive disease, but high risk features like big tumors that have grown into things in lymph node disease. Then pembrolizumab has an approval now in combination with enfortumab as initial treatment, but then also as second line treatment. Then avelumab has an FDA approval for what’s called maintenance, so after you get chemo, just to maintain a nice response.

Really, the reason that these have different approvals is just because the studies were done in different settings and the drug companies were all trying to figure out where to get their little place where they’d get an FDA approval. It’s very hard to tell there’s actually any difference between drugs. I will say that pembro and nivolumab are both anti-PD1 and have been successful in ways that atezolizumab didn’t meet its primary endpoint. It withdrew FDA approval. So whether there’s something to that, these PD1 versus PDL1, we’re not really sure, but people like to talk about it.

I don’t typically switch from one to another. There’s really not any good evidence that people will respond to one if they haven’t responded to another. Typically, our preference will be other treatments that we know work or clinical trials at that point.

Rebecca Johnson:

Thank you. I want to end with a question that’s not disease-specific but I think many patients probably grapple with and is relevant to any stage or diagnosis, and that’s the mental aspect of the diagnosis and of being diagnosed with cancer and going through treatment. How would you advise a patient or what would you say to them when they ask, “How do I get over the mental hurdle of worrying if today is the day the cancer returns or moves to another part of my body?” and either of you are welcome to comment on that.

Dr. Philip Abbosh:

I can start. It’s hard for me to … I haven’t had cancer, so for me to say, “Just forget about it,” is crazy. I can tell you my own experience with my family. Both my parents had cancer. My mom survived, my dad didn’t. My mom, every time she goes for her colonoscopy and for a CT scan, I worry. She was diagnosed in ’99. She had a really rough go with chemo and surgery and the whole thing, and then did great, and then had come back in her colon 12 years later. So that goes back to the question of, “Should I stop having cystoscopies from my T1 tumor that had happened 10 years ago?” Well, she was 12 years out and we stopped doing colonoscopies and CT scans and got kicked in the gut.

So certainly, not going gone through it myself, but having my mom go through it, I worry. I think it would be inhumane to not worry. Each person’s going to deal with that on their own way. I think my mom just gets quiet. I don’t really hear from her for a couple of days before. I know it’s coming. We both know it’s coming. I talked to her that night and you just hold your breath and brace for impact and hopefully everything will be fine.

So I think that’s a really tough question to answer. Just from my own experience with a family member, I don’t know that it gets any easier, and I apologize, there’s no magic recipe.

Rebecca Johnson:

Absolutely. Thank you for that answer. Tracy, I don’t want to cut you off if you want to contribute to that, but I want to make sure we have time to announce our awards as well.

Dr. Tracy Rose:

I don’t want to miss the awards too. I think Phil’s answer was beautiful. I think people are not alone and it is really hard.

Rebecca Johnson:

Absolutely. Well, as I said, we are coming to the end of our time. I want to thank you both so much for spending this time with us, answering the thoughtful questions that we had submitted by our patients and loved ones, and also just dedicating your careers and expertise to advancing the bladder cancer field in patients’ lives and partnering with BCAN. We’re very grateful to have your support and to work with both of you. So thank you so much.

Before we close, it’s my great pleasure to share with you the 2023 cohort of the BCAN Young Investigators. The recipient of our Patient-Centered Clinical Research Young Investigator Award, which is a unique Young Investigator award focused specifically on outcomes that are important and matter to patients is Dr. Rishi Sekar from the University of Michigan.

The recipients of our Young Investigator Awards are Jonathan Chou from the University of California, San Francisco, Sean Clark-Garvey at the University of North Carolina Chapel Hill, Kathryn Gessner, also at the University of North Carolina Chapel Hill, and Soonbum Park at Columbia University Medical Center. Congratulations to all of you and welcome to the BCAN Family.

I now also have the honor of announcing our BCAN of Hope Award recipient. As part of Bladder Cancer Awareness Month, we ask members of the BCAN community to nominate the special someone who served as a BCAN of hope and light in their bladder cancer journeys. We received over 120 nominations this year, and from those we had three finalists, Dr. Amy Luckenbaugh, an assistant professor in the Department of Urology and a surgeon at the Vanderbilt University Medical Center, Nancy Parrish, a bladder cancer survivor and the founder of the North Carolina Bladder Cancer Retreat, and Brian Billings, a bladder cancer survivor and the founder of the New York City Bladder Cancer Support Group.

BCAN received over 3,000 votes, a record, smashing the previous year, and it is my pleasure to announce the winner of the 2023 BCAN of Hope Award is Nancy Parrish. Nancy is a bladder cancer survivor and the founder of the North Carolina Bladder Cancer Retreat. One of the people who nominated Nancy said of her, “She is a bladder cancer survivor herself. Her dedication and love for others is evident from the moment you meet her. She paints and sells rocks to help raise money so that registration for the retreat can cost as little as possible for attendees. You are a stranger only once when you meet Nancy. From then on, you are a friend.” Congratulations, Nancy.

That brings us to the end of our program. Just a reminder that this will be available for viewing on the bcan.org website, that’s B-C-A-N dot org, in just a couple of days. I want to thank all of you for joining us, and thank you so much to our experts again, and for everyone’s support of BCAN and our bladder cancer community. Have a good evening.