Transcript: What You Need to Know About Upper Tract Urothelial Carcinoma:

May 23, 2024

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Voice over:

This is Bladder Cancer Matters. The podcast for bladder cancer patients, caregivers, advocates, and medical and research professionals. It’s brought to you by the Bladder Cancer Advocacy Network, otherwise known as BCAN. BCAN works to increase public awareness about bladder cancer, advances bladder cancer research, and provides educational and support services for bladder cancer patients and their loved ones. To learn more, please visit BCAN.org.

Rick Bangs:

Hi, I am Rick Bangs, the host of Bladder Cancer Matters, a podcast for by and about the bladder cancer community. I’m also a survivor of muscle invasive bladder cancer, the proud owner of a 2006 model year neobladder, and a patient advocate supporting cancer research at the Bladder Cancer Advocacy Network, or as many call it, BCAN, producers of this podcast. I’m pleased to welcome today’s guests, Dr. Jeannie Hoffman-Censits and Dr. Phil Pierorazio. Dr. Hoffman-Censits is a genitourinary medical oncologist at the Greenberg Bladder Cancer Institute and the Co-Director Women’s Bladder Cancer Program at Sidney Kimmel Cancer Center at Johns Hopkins. She attended Jefferson Medical College Medical School, and then spent her residency in fellowship at Thomas Jefferson University Hospital and the Fox Chase Cancer Center in Philadelphia, Pennsylvania respectively. Her clinical and research interests is in the development and treatment of novel therapies for cancers of the bladder ureter and renal pelvis.

Dr. Hoffman-Censits research focuses on urothelial cancers. Her clinical research has helped identify urothelial cancer subtypes and establish new treatments for bladder and upper tract urothelial cancers. She participates in the AUA/SUO Guideline panel for Upper Tract Cancers and is also a member of the BCAN Scientific Advisory Board.

Dr. Phil Pierorazio is professor of surgery at the hospital at University of Pennsylvania. He received his undergraduate degree from Georgetown University in Washington DC and his medical degree from Columbia University, where he also completed a Doris Duke Clinical Research Fellowship in Urologic Oncology. He is a board certified urologist with training and expertise in urologic cancers, and focuses on upper tract urothelial cancer, kidney cancer, testicular cancer, and prostate cancer. Dr. Pierorazio’s research focuses on access to care cancer biomarkers, improving outcomes for complex surgeries, evaluating quality of care throughout a cancer journey, quality of life for cancer survivors, and minimizing the impact of surgical treatments. He’s also involved in several national guideline panels, including the AUA, the American Urological Association, and the NCCN, National Comprehensive Cancer Network guidelines Committees for kidney, testicular and upper tract urothelial cancer. Dr. Hoffman-Censits and Dr. Pierorazio, thank you for joining our podcast.

Dr. Hoffman-Censits:

Thanks, Rick. It’s great to be here.

Dr. Pierorazio:

Yeah, wonderful being here, Rick.

Rick Bangs:

Glad to have you. So our focus today is on upper tract urothelial cancer. And so I wanted to start with some fundamentals, because, I think people would want to understand what exactly is the upper tract, where is it, and is it more than just the ureters, the tubes from the kidneys to the bladder?

Dr. Hoffman-Censits:

Rick, I’ll jump in and take this one. So I think a lot of people have heard about the bladder and we talk a lot about bladder cancer even you mentioned BCAN, the Bladder Cancer Advocacy Network, but the most common kind of bladder cancer is urothelial cancer and urothelium lines. It’s a tissue that lines the inside of the bladder and that bladder is contiguous with ureters, which are tubes that connect the kidneys, which filter blood and make urine. And then that urine is then transmitted into something called the renal pelvis, which is a small reservoir and into the ureters, which are straws that connect the bladder to the ureters.

So, if Dr. Pierorazio actually were to drive a scope through the urethra and then up into the bladder and into the ureters and renal pelvis on the inside, that’s all line with the same contiguous tissue and cancers that develop in the bladder, the ureters and the renal pelvis are all turned to urothelial cancer, if that’s the appearance and the histology that they have under the microscope.

Dr. Pierorazio:

And we have the distinction of upper and lower tract urothelial cancers for two major reasons. The first is, as Jeannie mentioned, clinically we look into the bladder. That’s kind of the downstream lower urinary tract. And then it takes a different set of tools and different skill set to get into the upper tract, which are the ureters and kidneys. And then the other reason is embryologically they actually form differently. Even though they have the same lining in our lifetime and especially in adulthood as an embryo, the kidneys and ureters develop in a different way than the bladder does.

Rick Bangs:

Wow, okay. So how would upper tract urothelial cancer be diagnosed? And is it harder to diagnose than the standard plain vanilla urothelial cancer?

Dr. Pierorazio:

Yeah, upper tract cancers are typically found the same way as bladder cancers with hematuria or blood in the urine. The trick is they are much more rare, so there’s only between nine and 10,000 cases per year in the U.S. You can extrapolate that around the world. Whereas there’s tens or hundreds of thousands, even patients walking around with bladder cancer or history of bladder cancer in the US at the same time. And the hematuria, or blood in the urine, tends to be more pronounced for bladder tumors. And so there often has to be a high degree of suspicion when you see hematuria or blood in the urine of somebody with upper tract disease. Rarely is it what we call gross hematuria where you look in the toilet and you see blood. Often it can be what’s called microscopic hematuria, which is only diagnosed by lab tests and a very astute physician.

Rick Bangs:

And so other than the blood in the urine, are there different symptoms for this as well?

Dr. Hoffman-Censits:

So Rick, that can depend. A lot of times these tumors are quite small and sometimes the blood in the urine, as Phil mentioned, can even be intermittent. True of both upper tract urothelial cancer as well as bladder cancer. And one of the reasons sometimes it takes patients, sometimes a long time to even come to a doctor’s appointment or have a diagnosis is you can bleed one day and then not be bleeding the next based on activity. Or there may be concomitant medications that someone takes aspirin or a nonsteroidal or something like that.

If upper tract tumors get big enough, they can cause pain, like flank pain, almost like a kidney stone would. But different than a kidney stone. These things tend to grow slowly over time. And the problem with that is the body can adjust to any kind of blockage that that tumor may have as opposed to a kidney stone, which there’s no blockage, one moment and a blockage next, and the body reacts to that. So sometimes there are no symptoms, sometimes blood and urine, sometimes again, flank pain like a kidney stone pain. Because of the blockage that can also sometimes lead to infections, something called pilot nephritis, which is a closed infection that can happen in the kidney. But unfortunately a lot of times the symptoms are quite subtle and either intermittent pink urine or even blood in the urine that’s too small to be detected.

Rick Bangs:

So it’s a little bit tricky. So can I have both bladder cancer, the plenal urothelial cancer and upper tract at the same time?

Dr. Hoffman-Censits:

You actually can have both at the same time. And in fact, if you have upper tract urothelial cancer, we worry that you could have a future lower tract or bladder cancer. So when you think about the anatomy of the kidneys, the ureters in the bladder, a tumor that starts from the renal pelvis, those cancer cells have to go somewhere so the urine carries them through the ureter and down into the bladder. So if a patient has an upper tract urothelial cancer that Phil resects, one of the workflows for surveillances, a need to look into the bladder with a cystoscope on an intermittent basis because we worry about a new bladder cancer coming about. Sometimes we see that initial presentation. Sometimes these things will happen in sequence.

Dr. Pierorazio:

And because these are a similar type of cancer, they’re both urothelial cancers, we think about two main of cancer that play off each other. One is the underlying genetics, these are the genetics of those cells, not necessarily the germline genetics we talk about that you’re born with. But there’s some kind of genetic defect in your urothelium that makes you more prone to a cancer. And then there’s exposure to toxins or urine. And because we think the urine sits much longer in the bladder than it does in the upper tract, you’re more likely to have bladder tumors and bladder cancers and upper tract disease. But Jeannie’s absolutely right. You can form them in both places. And we do worry about seeding with these cancers. Meaning tumor cells can kind of poke off or float off of the upper tract and they’ll land in the bladder. Because of the natural mechanisms we have in our urinary system, urine tends not to flow upwards into the kidney. So it’d be rare for a bladder cancer to ascend, although that certainly can happen as well.

Rick Bangs:

Okay. So, Dr. Pierorazio, Let me ask you a question. If you suspect I’ve got blood in the urine, you suspect something’s going on and you do the cystoscope, how would you rule out that I didn’t have any upper tract at the same time? Is that based on imaging or how are you figuring out that there’s also no upper tract?

Dr. Pierorazio:

Yeah, this is called the hematuria workup, and this is standard, and there are very good guidelines from the American Urologic Association about how to work up patients who present with hematuria, either gross or microscopic. And without going into too much details because that’s beyond this podcast, basically patients need an evaluation of their lower tract, which is a cystoscopy, and they need an evaluation of the upper tract, some form of imaging to show us that the kidneys and ureters are okay. Depending on their risk factors developing disease, depending on their history, family and personal, depends how invasive and what kind of testing we order. But yeah, you’re absolutely right. We need some kind of imaging of the kidney and ureters and we need some direct evaluation of the bladder, typically a cystoscopy.

Rick Bangs:

And are these cells different? And obviously they’re in a different location, but is it more than that? Are they actually different in adulthood?

Dr. Pierorazio:

No, they’re actually identical, the urothelium and it actually turns over. So every few days the urothelium is changing itself over cells or sloughed off, destroyed part of the body’s natural process just like your hair grows or your fingernails, same kind of thing. The urothelium is constantly regenerating and regrowing. The cancers are similar yet slightly different though. There are similar genetic defects in upper tract urothelial cancers as there are in bladder and vice versa. But the predominance of genetic defects are slightly different. So we don’t need to necessarily get into the genes, but there are certain genes that tend to drive upper tract tumors as opposed to lower tract or bladder cancers.

Rick Bangs:

Okay. All right. And so Dr. Pierorazio, this question is for you. So the location seems like it would make treatment challenging, and I’m going to start with you. So what are some of those challenges?

Dr. Pierorazio:

Yeah, it’s actually one of our most challenging diseases, because we lack really good diagnostic tools. And most of the reason we lack the tools is because of our anatomy. In most people, the ureter is about the size of a shoelace, and so now you have to be able to get an instrument up that shoelace to be able to see and then get an instrument that’s even smaller through that to be able to get biopsies or tissue or some form of evaluation. So yeah, we have lots of diagnostic challenges in this space. The first one is getting tissue and really getting an answer. And that’s why the new AUA/SUO guidelines really mandate that we should be driving our management decisions based on tissue and we should be doing everything we can to get a tissue diagnosis for patients with upper tract tumors.

Rick Bangs:

And so what’s the prognosis for a patient with upper tract? Is it more or less deadly than the plain vanilla urothelial bladder cancer?

Dr. Pierorazio:

We’ll say it this way, grade for grade and stage for stage, they’re actually similar. Grade refers to how aggressive a cancer looks under the microscope. Stage refers to its invasion either into the urinary system or beyond. And so they’re actually relatively similar. So the prognosis is excellent if you have a low-grade non-invasive tumor in terms of your overall survival, meaning your likelihood of dying of this kind of cancer is incredibly low if it’s low-grade and non-invasive. But on the flip side, high-grade invasive urothelial cancers are the ones that are more likely to spread. And if they spread, the prognosis is really challenging. And these are patients who are going to need to be treated with systemic, the chemotherapies, immunotherapies, et cetera, which Jeannie is an expert in. And even with great responses, the prognosis is still guarded. We don’t know who’s going to respond well and who’s ultimately going to succumb to the disease.

Rick Bangs:

And are you more likely to find, diagnose me later if I have upper tract versus the blood?

Dr. Pierorazio:

Yeah, that’s the major difference, is we are more likely to find more advanced high-grade disease in the upper tract because of the diagnostic issues. They’re less likely to present with gross hematuria. They are often mistaken for urinary tract infections because there’s not a lot of other symptoms related to them. And so patients are more likely to present with advanced stage, with advanced stage less favorable survival.

Rick Bangs:

All right. And so now let’s talk a little bit more about the treatments that are available. So where do we usually start the treatments?

Dr. Pierorazio:

Yeah, so the first part, as I said, is you’re really going to need a good diagnostic workup. So that is typically a ureteroscopy with a biopsy and sampling of that tumor. We’ll often take washings of the urine around the tumor as well because we’re trying to maximize our ability to distinguish a low-grade versus a high-grade cancer. And that will really determine the next treatment steps. In general, low-grade tumors are non-invasive. It’s very rarely will they invade into the urinary tract. So we have all forms of topical or what we call endoscopic treatments available to us.

We try and spare kidneys and try and save as much as we can, because we know patients are at risk of developing tumors down the road. And so we don’t want to just take out a kidney or take out a ureter because there was a tumor in it. We try and keep those things intact. High-grade cancers are very different and we’ll talk a lot more about them. Yes, some patients may be eligible for what we call ablative strategies, but most patients with high-grade tumors, we’re talking about radical surgery, which is removal of the entire kidney and ureter as well as systemic therapies.

Rick Bangs:

So someone who’s had a kidney stone, I need to ask is the scoping and the equivalent to I guess the T-U-R-B-T, is that going to be more painful and uncomfortable for me?

Dr. Pierorazio:

Yeah, it’s usually not, believe it or not. It’s usually less. And the reason is we are not often up there as long as you are when you’re having a kidney stone treated. And the idea is when you have a kidney stone, the urologist needs to go up there and relieve that obstruction, and that obstruction is a hard piece typically of calcium that needs to be blasted apart with a laser. It needs to be washed around and all of those fragments need to be retrieved or removed from kidney. So there’s a lot of manipulation of the ureter and the kidney. The first ureteroscopy you’re going to have for a upper tract urothelial cancer is typically relatively straightforward under an hour. We kind of like to use the term diagnostic urethroscopy. We’re going up, we’re getting tissue, we’re learning everything we can about this. We may do some manipulation, may try and burn or buzz a tumor, but in general, we’re not spending an extended period of time up there.

Most of us no longer like leaving stents in after treating these tumors. Stents are soft plastic tubes that allow urine to drain after a procedure. Sometimes after ureteroscopy, particularly after a stone procedure, the ureter can get really swollen and block off urine and then you feel like you still have the stone. In upper tract disease, we tend not to do as much drastic manipulation, so there tends to be less swelling. And we know leaving a stent in can increase that phenomenon I talked about before of seeding. So we don’t like to leave a stent in because that can promote actually tumor cells coming down the ureter and implanting in the bladder. Sometimes we don’t have a choice and we have to leave a stent, but often we try to leave patients stentless as well.

Rick Bangs:

And my recollection is that stents are a little tiny bit uncomfortable.

Dr. Pierorazio:

This is the way I always put it. 95% of patients know they have a stent there. A hundred percent of patients know they have a stent there. 95% of them, it’s tolerable. The other 5%, it’s miserable. Everybody knows there’s a stent in place.

Rick Bangs:

Okay. All right. So when I was having trouble sleeping with a stent in, it was not my imagination. So who do I get my treatment from if I’ve got upper tract? Are there specific specialists, urologists that specialize in the upper tract, and is the urologist playing the same role that they normally play in bladder cancer? How does that work?

Dr. Pierorazio:

Yeah, this is one of those times where you really to ask your urologist’s experience, most people are going to be diagnosed by a general urologist, someone in their community who sees this and does the initial workup. That is completely appropriate and that person should be putting a ureteroscope up, they should be trying to find out what’s going on and they should be trying to make a diagnosis particularly of an upper tract urothelial cancer, low versus high grade. This is one of those diseases that’s rare enough, only nine to 10,000 per year in the US, that you really should feel comfortable asking your urologist how many of these do you see and treat? If you don’t do a ton of them, who in your practice or what academic center nearby sees a lot of these? Because the decisions are actually very nuanced in the management of this disease, because it is so rare and because there’s so many variables at play.

Rick Bangs:

Okay. And I know a lot of patients are going to be concerned about their kidneys. So do kidneys have to be removed always if a patient’s been diagnosed with upper tract? Can you save the kidney? And what are the differences in treatments between low and high grade?

Dr. Pierorazio:

Yeah, great question Rick. And the question first starts with what is someone’s baseline kidney function and how many kidneys do they have? So most people have two kidneys. Most people’s kidney function is at a level where if a kidney was removed, they would not experience any detriments in their lifetime. And for a normal healthy patient with two kidneys who has a kidney removed for any reason, the chance of progressing to what we call chronic kidney disease and stage renal disease and dialysis is less than 2%. It’s incredibly rare. However, upper tract urothelial cancer tends to be disease of the elderly. Not always, but tends to be patients who are older and sicker. And all of us, as we get older, we don’t run as fast and jump as high as we did when we were younger. And our kidneys don’t filter as well as they do when they’re younger either.

And so depending on how much kidney function we’ve lost as we age can really help or it’s really important consideration in trying to pick treatment. So in someone who removing a kidney would put them on dialysis, that’s a really big decision and we will do almost anything we can to keep somebody off dialysis because we know that’s a huge detriment to quality of life, and it actually has long-term implications for their life expectancy. In someone who has two healthy kidneys, depending on the tumor, low grade versus high grade, it is completely acceptable to remove a kidney when and if we need to.

Rick Bangs:

Okay. So I’ve heard about surgical treatments, but I think there’s a new mitomycin gel. So mitomycin is often used in bladder cancer, but now this is gel version. How does that work and for whom is that relevant?

Dr. Pierorazio:

Yeah, it’s a great question, Rick. I’ll try and keep this brief and then ask questions if you want me to be more specific. But in general, bladder cancers have been treated for decades with topical therapies. There is something called BCG, which is basically an immune booster that helps prevent bladder cancers from coming back once they’ve been removed. There are topical chemotherapies like mitomycin or gemcitabine are the most common ones used now, that will actually destroy or kill bladder cancers where they sit in the bladder with a little bit of dwell time. But the key is these chemotherapies need to touch the tumor for them to be effective and work. In the upper tract, because the kidneys are constantly making urine, it’s hard to get these agents to dwell.

So for decades we’ve been using BCG in the upper tract, it has to be dripped in, and these are patients who have carcinoma in situ you and no evidence of a tumor, but a high-grade cytology that is an effective therapy. And now, as of the last few years, there’s a product called Mitagel or the eUROGEN 101 product, which is a hydrogel, a reverse thermal hydrogel, which is really complicated sounding. But basically this is a liquid at room temperature or actually when cooled a little bit when it is injected into the kidney or anywhere in the body and it warms up, it actually solidifies, which is not typically how we think about liquids.

But then as it solidifies, it dissolves and it can be impregnated with a variety of medications. And in this case it’s impregnated with mitomycin C, which is a chemotherapy which is highly effective at killing urothelial cancers. So for patients who have low grade upper tract urothelial cancer, mitomycin gel is extremely effective with greater than 60% efficacy in majority of patients who were treated at eradicating or ablating, low-grade, upper tract urothelial cancers. And then of late for patients who have high-grade disease, we know that that mitomycin product is not terribly effective. There’s been new data out of the University of Iowa using topical gemcitabine and docetaxel, which is a cocktail that was developed for the bladder in treating some patients who have high-grade, upper tract urothelial cancers. The response rate is a little bit less. It’s probably more in the range of 30 to 50% depending on the size of the tumor and the patient. But we do have topical ablative strategies for both patients with low-grade and high-grade tumors now.

Rick Bangs:

Wow. So the gel brings along mitomycin, and the gel is the platform which is at body temperature solidifying and the mitomycin is included in the gel.

Dr. Pierorazio:

Correct.

Rick Bangs:

Fascinating.

Dr. Pierorazio:

And actually there’s a product for the bladder as well.

Rick Bangs:

Wow. A gel.

Dr. Pierorazio:

A gel.

Rick Bangs:

Wow. Interesting. All right, Dr. Hoffman-Censits, talk to me about clinical trials and promising treatments that you are aware of?

Dr. Hoffman-Censits:

So in terms of thinking about the medical oncologist role in systemic or intravenous chemotherapy for upper tract urothelial cancer, I think Phil defined the differences between low-grade disease, again, more often treated with topical therapy with the goal of keeping the kidney intact. But for high-grade disease, those patients ultimately are best served with a surgery for the kidney to come out. Because we’re treating urothelial cancer, we really borrow or extrapolate what we do as a medical oncologist from how we know how to treat lower tract disease or bladder cancers. So for muscle-invasive bladder cancer, for decades we’ve been using a cocktail of chemotherapy, either one of two cocktails, both of which have a backbone with a drug called cisplatin. It’s an effective drug, but also one that has a lot of toxicities that go along with it. And unfortunately in our older population that have other medical problems, about half the patients who we feel like would be good candidates from a tumor perspective really are not eligible. It’s not safe to give them that medication.

But for those who can tolerate it, we know that giving cisplatin in the pre-operative setting before bladder cancer is removed, that then improves overall survival. So we’ve done some work in trying to do that same treatment paradigm for patients with upper tract disease. Again, carefully selecting patients that may be good candidates for that. A little bit more tricky in thinking about that for upper tract urothelial cancer and the timing, we like to offer it in the pre-operative setting, but as Phil said, these tumors can be pretty hard to stage and from a biopsy perspective as well as a radiographic perspective. And then also the implications of giving that treatment maybe even higher because the patient at the end of the day is going to lose a kidney. And cisplatin is both potentially toxic to the kidneys as well as metabolized by the kidneys.

So the nuances I think are, like Phil mentioned, are really important thinking about how we would use those medications importantly, both for bladder cancer as well as upper tract urothelial cancer. If a patient has a high-grade tumor and we’re concerned about invasion and they get chemotherapy, finish their chemotherapy, move on to surgery, the pathologist that works with us after Phil would remove a kidney, gives us this vital information about did the tumor live through that chemotherapy, and if so, what is the final pathologic stage? And were lymph nodes involved. That’s incredibly important information to help us guide next steps in care.

As you can imagine, those patients that have a tumor that’s super sensitive to that chemotherapy where there’s, what we call a complete pathologic response, just a wasteland where the cancer used to be, those patients have the better long-term outcomes. We’re continuing to do follow-up with surveillance scans cystoscopies, but for those that understandably, if the tumor lives through that chemotherapy, especially if lymph nodes are positive, we really worry that that cancer can come back and come back quickly. And so we then have the opportunity to counsel those patients about other kinds of treatments in the post-operative setting.

Rick Bangs:

Okay. So Dr. Pierorazio, any insights you want to provide on clinical trials, maybe diagnostic or surgery agents, customizing the right treatment of the right patient? Any and all of that and more?

Dr. Pierorazio:

To my knowledge, nothing really in the diagnostic realm. There’s some really smart bioengineers who are working on improved diagnostics for a variety of diseases. There’s nothing I’ve seen that’s been particularly exciting for upper tract disease to be honest with you. I think the two exciting avenues now are one, these topical or ablative strategies and that mitomycin product completely changed the way we think about urothelial cancer, and using ablative strategies, chemo or chemical ablative strategies to give us more effective kills rather than just relying on inadequate instrumentation, to be honest with you, in the upper tract. So I think that’s one really exciting area, and that’s just the tip of the iceberg of products I think we’ll see in the upcoming years.

I think the second area is really this inclusion of systemic therapy. We know invasive urothelial cancers are systemic disease. These are cancers that can spread around the body, that have spread around the body. And right now we err on the side of systemic therapy. Jeannie and I are both huge advocates for what we call neoadjuvant chemotherapy or neoadjuvant therapies because we understand that we may be hedging our bets a little bit. We may over-treat a few people, but in the case that you have a kidney removed and can’t get these life-saving therapies, that’s when we feel the worst, to be honest with you. And that’s when patients and their families feel the worst.

So now that we have better agents, now that we’re better understanding this disease, understanding how we can tailor the therapies and better select patients who needs therapy up front, what therapy should they get? What order should we do these things in? That’s becoming the nuanced and exciting part of this field. And then I’ll just add one last thing that I think is really important for people to hear too is bladder cancers in general are not genetically related, but there is a fair proportion of patients with upper tract disease that have genetic syndromes. The most common one is Lynch syndrome. We are understanding much more about Lynch syndrome, how that affects patients with upper tract disease and how they may respond differently than other patients. So I wouldn’t necessarily call these clinical trials, but I think these are three exciting areas for future discovery and future directions for this disease.

Rick Bangs:

Excellent. Well stay tuned. That sounds exciting. So Dr. Hoffman-Censits, any final thoughts?

Dr. Hoffman-Censits:

So I agree with what Phil was saying in terms of really understanding the biology of these tumors a lot better. Previously, I think upper tract urothelial cancer was a little bit forgotten, so rare, difficult to diagnose complications and things like that. I think more and more we’re thinking about this in the community of people who take care of the disease for a living, its own entity. As you earlier, both Phil and I are super proud of these new upper tract urothelial guidelines. This publicly available essentially book for neurologists and medical oncologists about how do you work this up in what order? Again, the nuances and the subtleties of windscope and how to do it, and then the use of these pre and post-operative therapies. Having that space, having that available published and actually even thinking about clinical trials in upper tract disease is a change from the last 5 to 10 years, which I think is really important.

There’s a lot more attention being paid to the space and the fact that there are some biological differences that I think we can potentially capitalize on, which is quite important. There’s a lot of new medical therapies, oral therapies as well as intravenous therapies that have been FDA approved for advanced urothelial cancer. That’s how most of the time drugs get approved. Maybe gel, a different approval process. But I think one thing to think about is how do we use those newer, more effective tools that are less toxic maybe than cisplatin-based chemotherapy? How do we use them in the pre and post-operative setting?

We’re starting to answer some of those questions, which I think is great. And then in terms of clinical trials, there is a large national clinical trial that we have ongoing. I’m proud to be leading that study that’s looking at a cisplatin backbone of chemotherapy with or without one of the intravenous immunotherapies that are FDA approved for urothelial cancers. We know that in the advanced setting for those with metastatic either bladder or upper tract tumors, in the last 12 months, two regimens have been FDA approved and shown survival benefit over just chemotherapy alone that the showed that chemotherapy plus immunotherapy and provides better outcomes. So we’re looking at that in the preoperative setting in this trial.

Rick Bangs:

Excellent. Really exciting. Really exciting. Dr. Pierorazio, how about you?

Dr. Pierorazio:

Yeah, I just want to echo what Jeannie had to say. I think it’s an exciting time for this disease. I think we’re seeing dramatic changes, and I think it’s finally getting recognition as an important disease states that warrants attention. And just, I think a good analogy to that is if you look at every major bladder cancer trial now has a carve out that there has to be so many upper tract urothelial cancer patients in there. And there’s two reasons for that. Well, there’s more than two reasons, but two major ones. First, we would never get that trial done in upper tract patients. There’s too few of those patients, too many sites around the world. And so bringing them into the urothelial cancer in general makes a ton of sense. And second of all, it really recognizes how important this disease is and how much we learn by taking care of these patients.

And it’ll help our understanding of cancers in general, help our understanding of bladder cancers as well. So I think that is a good analogy to understand why it is so important and how it’s getting recognition. But I think it’s a truly, as I said, exciting space to work in as a clinician, as an academic person, as a researcher, we have lots of really exciting questions. They’re getting answered. We have the opportunity to make big differences, and we have an opportunity to make big differences in people’s lives at an individual basis too, because Jeannie and I can tell you, we probably remember the vast majority of patients we’ve treated with this disease because there are relatively few of them compared to the other diseases we see. So thanks for your time, Rick.

Rick Bangs:

Yeah. Appreciate it. And Dr. Hoffman-Censits and Dr. Pierorazio, thank you for providing us an overview on upper tract urothelial cancer and what a patient should know about this diagnosis and treatment. If you’d more information on bladder cancer, please visit the BCAN website, www.bcan.org, in case people wanted to get in touch with one or both of you, could you share an email, a Twitter handle, or other information you would like people to have? Dr. Hoffman-Censits, how about you?

Dr. Hoffman-Censits:

Sure. On Twitter, I’m @JCensits.

Rick Bangs:

That would be J-C-E-N-

Dr. Hoffman-Censits:

S-I-T-S. Yep.

Rick Bangs:

Dr. Pierorazio, how about you?

Dr. Pierorazio:

I’m at the University of Pennsylvania now, and you can find my email on that website, or it’s my full name, philip.porazio@penmedicine.upenn.edu. Or you can also find me on social media. Twitter’s probably the easiest @doctorphil_urology.

Rick Bangs:

@doctorphil. Love it. Just a reminder, if you’d more information about bladder cancer, you can contact the Bladder Cancer Advocacy Network at 1-888-901-2226. That’s all the time we have today. Be sure to like, comment and subscribe to this podcast so we have your feedback. Thank you for listening, and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again and Dr. Hoffman-Censits and Dr. Pierorazio.

Speaker 1:

Thank you for listening to Bladder Cancer Matters, a podcast by the Bladder Cancer Advocacy Network, or BCAN. BCAN works to increase public awareness about bladder cancer, advanced bladder cancer research, and provide educational and support services for bladder cancer patients. For more information about this podcast and additional information about bladder cancer, please visit bcan.org.