Transcript of “Bladder Cancer and the Slippery Slope of Radical Cystectomies” with Dr. Ashish Kamat

March 9, 2021

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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 B-C-A-N dot O-R-G.

Rick Bangs:

Hi, I’m 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. This podcast is sponsored by FerGene and Merck. I’m excited to have Dr. Ashish Kamat back for a return visit. If you didn’t catch him on our inaugural podcast regarding BCG, where I went through his impressive bio, Dr. Kamat is a professor of urology and director of eulogic oncology fellowship at MD Anderson Cancer Center in Houston, Texas. He’s also a member of the Bladder Cancer Advocacy Network’s scientific advisory board. In today’s episode, we are going to talk about what I call the slippery slope, high grade non-muscle invasive bladder cancer.

Rick Bangs:

I call it the slippery slope because in some cases, the patient may at a later time need to have the bladder removed along with the prostate in men in a hysterectomy and women. Decide too late, and the cancer may have progressed. Decide too early, and your quality of life is negatively impacted sooner than necessary. Knowing when the patient should make this decision is both an art and a science and requires clear guidance from an expert medical team. Dr. Kamat, welcome back and thank you so much for joining us to talk about the slippery slope today.

Dr. Ashish Kamat:

It’s always a pleasure to be with you, Rick, and answer any and all questions that you have ready to throw at me.

Rick Bangs:

Okay, here it comes. I want to start with some foundational information because this is really all about managing risk. Suppose I just got diagnosed with bladder cancer and the doctor told me the grade of my bladder cancer, what is grade and what are the relative risks of the various grades?

Dr. Ashish Kamat:

Yeah, one of the first things that patients will often be told when they sit down and hear about the diagnosis of bladder cancer is the grade of disease and the stage of disease. And essentially the way to think of grade is the personality of the bladder cancer that the patient has. So when we look at grade, essentially under the… Scientifically speaking, we’re looking at the cancer cell under microscope, we’re looking for clues as to how aggressive it looks, what its potential behavior is. And that’s what high grade cancers are. Those are cancers that have features that make them aggressive.

Dr. Ashish Kamat:

And then low grade cancers are still cancers, but they have features that are less aggressive. And in the case of bladder cancer, when you have a low grade or a less aggressive cancer, that is called low grade, those tumors will very rarely be a threat to the patient’s life. But the high grade cancers can be a threat to the patient’s life, even if they’re small. So the grade essentially, is a way of thinking of personality of the cancer cell and for bladder cancer is they’re broadly divided into low grade and high grade cancer.

Rick Bangs:

Okay. So I’m wondering if the personality of the cancer can change, can low-grade eventually become high-grade?

Dr. Ashish Kamat:

Yes and no. So from a patient perspective, it matters. The question often is asked, I have low grade cancer now, can I ever get high grade cancer? And from that specific question point of view, yes, a patient can certainly develop high-grade cancer after having initially be diagnosed by with low grade cancer, but there is a growing body of evidence to suggest that it’s not actually the low grade cancer that became high-grade cancer. It was just that that patient eventually develop a separate high-grade cancer, or maybe the high grade part of the initial tumor was missed on the initial diagnosis.

Dr. Ashish Kamat:

But if you’re asking me a purely scientific question in the sense that can a tumor that’s low grade today, that specific tumor become high grade? That is extremely rare. But can a patient have high grade cancer months or years after having had low grade cancer? Then the answer to that question is absolutely. And that’s why we monitor patients even if they have low grade cancers that are not really a threat to his or her life, because that tumor can become high grade in the sense that that patient can develop a high grade tumor down the road.

Rick Bangs:

So it sounds like the risk is relatively low for most patients who are low grade.

Dr. Ashish Kamat:

In absolute numbers, the risk of a low grade tumor becoming high grade is less than 10% at about 10 years.

Rick Bangs:

Okay. All right. So let’s get back to the pathology and what does stage refer to?

Dr. Ashish Kamat:

So if you sort of follow the analogy that I was alluding to, as far as the grade being the personality of the cell, then stage is how aggressive that cell has actually behaved already. So if it’s a high grade tumor that tumor could have been picked up early when the stage was low, even though that tumor has the potential to become more aggressive in the sense of more invasive, which correlates with stage. So in other words, when we stage a tumor, we’re now not looking at the personality of the cell per se, but we’re looking to see what actually that tumor has done. And if you think of the bladder, like a balloon, it’s got the same shape as a balloon, it’s got the cap, the sides, and then the neck. Now think of that balloon, the rubber of the balloon being the muscle of the bladder.

Dr. Ashish Kamat:

There are two layers on the inside of this rubber, there’s the rubber itself and there’s layer on the outside. So when these tumors start, they all start on the innermost layer and that’s what gives them a stage TA or CIS. And then they go down and send the roots down towards the muscle of the bladder or the rubber of the balloon, so to speak. So once they get into the muscle of the bladder they’re stage T2. When they get beyond it, they can be T3. If they go to the lymph nodes, they can be M plus and metastatic diseases, M plus. But that’s all stage. So a high-grade tumor is the one that is likely to go from low stage non-invasive or TA T1 to invasive T2 and more. Low grade tumors are very unlikely to go from a low stage to a high stage.

Rick Bangs:

Okay. And what percent of patients would start inside the balloon or non-muscle invasive bladder cancer?

Dr. Ashish Kamat:

That’s a question that I will answer, but I do want to preface that by saying that a lot of the stage distribution data that we and everybody quotes is based on historic series. More modern data haven’t really been robust enough to give absolute numbers. But if you look at historic series, on an average about 75% of patients will present or initially be diagnosed with non-muscle invasive disease and roughly 25% will have more advanced stages of disease, which includes metastatic disease. So when we’re actually looking at the burden that our patients face, the majority of patients by far will initially be diagnosed with noninvasive disease, and it’s a little bit unfair to just the way things move in our bladder cancer community that these patients used to be called or used to be classified as having superficial disease, which clearly is not something that should be used anymore because they’re non muscle invasive, but they’re not superficial per se. They’re just superficial to the actual muscle layer of the bladder.

Rick Bangs:

Yeah. I’m glad we changed the name of that because it just sounds so innocuous to be superficial.

Dr. Ashish Kamat:

Right.

Rick Bangs:

When you get a pathology report, is the staging ever wrong?

Dr. Ashish Kamat:

So let me answer that in two ways. Number one, can the pathologist make a mistake? Yes. Mistakes can occur and they may be pure human error, or there may be an error that’s made because the sample that was sent to the pathologist by the surgeon that removed the tumor was not adequate. It wasn’t handled properly. It wasn’t assessed properly. So if you’re asking me that short, I mean that can occur, but let’s assume that the urologist and the pathologist, all did their jobs just exactly the way they should, even then the staging can be incorrect. And clinical under staging is a big problem in patients with bladder cancer. Because what happens is that these tumors invade the different layers of the bladder that I was talking about, and the balloon analogy. But now, again, switching back to these layers, the bladder is not very thick.

Dr. Ashish Kamat:

It’s a very thin Oregon. In men, it’s not thicker than maybe a pair of jeans folded over, right? And we’re looking at the invasion of the tumor within these different layers. And people have tried to use CT scan and MRI. And in studies that we did here at MD Anderson and many others have replicated imaging is worse than flipping a coin because a CT scan is wrong more than half the time when it comes to differentiating between stage TA, T1 and T2, for example. It’s better when it comes to staging metastatic disease and MRI is a little bit better than CT in some situations. But it’s very important that we as the physicians taking care of the patient and the patient themselves recognize that staging is not 100%. And that’s why we’re constantly working on ways to improve the way we stage our patients.

Rick Bangs:

Okay. So the risks here are becoming a little bit clear. I want to go back to the high grade non-muscle invasive bladder cancer patient. How often would a patient in that category move into muscle invasive bladder cancer?

Dr. Ashish Kamat:

You know, right there, assuming the patient gets treatment the way they should. Fortunately today in the year 2021, that number is much lower than was the case even say 20 years ago when we first started looking at this. So let’s assume somebody has a high grade non muscle invasive has a bladder cancer today has been appropriately diagnosed and resected, and then is put on appropriate therapy, which is immunotherapy with BCG. The risk of that patient progressing to muscle invasive disease is 10% or so. It’s not much higher than that.

Dr. Ashish Kamat:

And if you look at older series, just as recently, as from the 1990s or even early 2000s, that was quoted as being as high as 30%. So clearly with better diagnosis, better optical enhanced cystoscopy, better recognition of the fact that patients should get not only induction BCG, but go on a full three year course of maintenance therapy if they have very high risk disease, the progression to muscle invasive disease is now 10% plus or minus a few percent. So 90% of patients will not progress. But again, we have to recognize that these tumors can recur. And it is very, very important that when these tumors recur they’re treated appropriately, because if they’re not treated appropriately, then clearly that 10% number is no longer true because poorly treated tumors will progress much more than just 10% of the time.

Rick Bangs:

It’s great to hear about the progress that’s being made because 30% down to 10% that seems to be a pretty decent improvement. Let’s pause for a moment, for a word from the Bladder Cancer Advocacy Network.

Speaker 1:

The Bladder Cancer Advocacy Network, BCAN, invites you to join us for our 10th annual virtual walk to end bladder cancer, Saturday May 1st, 2021 at 11:00 AM Eastern time. Our virtual walk is an interactive nationwide alternative to in-person walk events that involve thousands of participants walking from the place of their choosing. The overarching walk theme is no one walks alone as we make people aware that they are not walking alone during their difficult bladder cancer journey and important reminder during this time of social distancing. Critical funds raised through the virtual walk, help BCAN increase awareness about one of the most commonly diagnosed cancers in the US support hundreds of thousands of people living with this disease and raise funds for much needed bladder cancer research. The virtual walk will be broadcast on BCAN social media channels, and we’ll include compelling videos from bladder cancer patients, caregivers, doctors, and more. Learn more about the May 1st virtual walk to in bladder cancer at beaconwalk.org. That’s B-C-A-N, walk.org, or contact us at (301) 215-9099.

Rick Bangs:

We’re back with Dr. Kamat talking about high grade non-muscle invasive bladder cancer, AKA the slippery slope. So I want to kind of close the risk factors by talking about the TURBT, which is that surgery that you would perform to remove the tumor and that would be used to do the pathology. And I think most patients think, “Well, if the doctors removed the tumor, then the cancer has been removed.” But is that true? Is that something people should think that when they have the TURBT the cancer is gone?

Dr. Ashish Kamat:

So boy, Rick, you’re asking me all the tough questions today. Let me try my best to answer that in a succinct manner. So first off the Transurethral Resection of a Bladder Tumor is probably one of the most complicated surgeries that we perform for patients with bladder tumor. And that may come as a surprise to you because people talk about radical cystectomy, creating neobladder. Everyone’s focused on advanced in robotics and what have you, but the incremental benefit in those fields to the patient per se, for example, what the robotic cystectomy it is minimal. I mean, in hands of good surgeons, there is no difference between robot and open surgery other than maybe half a day less in the hospital. But there’s so much, so many dollars and hours at conferences that are poured into that debate and discussion.

Dr. Ashish Kamat:

On the other hand, the TURBT, which is the resection of the tumor, which was the first most critical step that the patient undergoes in his or her journey through robotic cancer is often ignored. In fact, in many parts of the world, it’s relegated to the junior most trainee or the junior most faculty, but that initial step where we go in, we look in the bladder, we identify the tumor, we resect either all the tumor as deep as you need to go, if it’s a high grade tumor or do as minimal a resection as you need to do if it’s a low grade tumor so we’re not unnecessarily traumatizing the bladder, that is a very complex procedure.

Dr. Ashish Kamat:

And in fact, not just me, I mean, the whole community is trying to get people to recognize that. And just very recently in the last couple of months, we published white papers and almost a call to arms that we need to improve the quality of the resection. Now, if the resection is done well, and by an experienced surgeon, then yes. The goal is to remove all papillary tumor. All visible papular tumors should be removed. and when the patient is started on treatment for his or her bladder cancer, there should be no tumor present in the bladder because intra vesical immunotherapy, even chemotherapy doesn’t really work well if this tumor left behind in the bladder.

Dr. Ashish Kamat:

Now it’s a little different when you’re talking about carcinoma inside tube because that is cancer. And in the bladder, a CIS is a little bit different than CIS in the breast or any other organ where it’s sometimes considered to be pre-cancerous. In the bladder CIS is still cancer. All it implies is that there’s a field defect and multiple areas in the bladder are one thing to form tumors, but haven’t actually formed a papillary tumor yet. So it’s very hard to CCIS and this remove the entire lining of the bladder. So in patients that have CIS all the visible areas are removed or cauterize, but there can still be cancer cells, CIS left behind in the bladder when that patient starts treatment.

Dr. Ashish Kamat:

And in that case, the goal of the TURBT is not to remove the entire bladder, obviously, but we do knowingly put that patient on treatment with quote unquote cancer left in place. But to summarize the goal of a well performed TURBT should be to remove every visible papillary tumor. I think short of that is really suboptimal, but CIS by its definition will often remain because you just can’t remove that unless you remove the entire block.

Rick Bangs:

And CIS would fall into a high grade bladder cancer category?

Dr. Ashish Kamat:

Yes. So the personality of the cell that is classified as CIS is the same as a personality of a cell that’s high grade TA or T1, and they all fall in the high grade category. And if you look at different risk classifications, as far as high risk bladder cancer, CIS is a high risk bladder cancer.

Rick Bangs:

Okay, great. So I think we’ve kind of clarified some of the risks that define the slippery slope. Let’s move into a discussion around the radical cystectomy. So that’s a very serious operation that’s going to include not just the removal of a bladder, but prostatectomy in males, hysterectomies and females, and most patients are afraid of cancer and they want to get it removed from their bodies as quickly as possible. And I know I fell into that particular category. So patients may not properly consider the long-term quality of life issues, issues like sexual function and continence, ability to exercise and do physical activities. They’re very focused on saving their life and the radical cystectomy is seen as doing that. So how can patients be confident they are getting all the information they need to make informed decisions and that they won’t have bias remorse after choosing a radical cystectomy?

Dr. Ashish Kamat:

Quality of life is extremely important, right? And it’s important at all stages of bladder cancer as it is with all cancers. And it’s very, very important that patients in many ways consider themselves as equal partners in this journey that they’re going through with their creating physicians. So I encourage my patients always to go to BCAN’s website and look at all the information that’s on there to hear stories of other patients. And then if they haven’t already come back and ask questions that they still have in mind, because I will go through a thorough discussion with my patients. My team will go through a thorough discussion with my patients, but it’s the Q and A, the question and answer, kind of what we’re doing today. That really is where people get their doubts clarified. Quality of life is very important, but it’s also important to recognize that everybody has different requirements when it comes to what he or she considers important for their quality of life.

Dr. Ashish Kamat:

So for example, after a radical cystectomy, as you alluded to the different ways to divert the urine, right? You can make a neobladder, you can go with an ileal conduit and there is no one size fits all. I’ve had patients who to me would appear to be perfect candidates for neobladder, but when you talk to them and they do their research like, “You know what, I don’t want a neobladder. I want to need an ileal conduit. I don’t want to mess with this neobladder business. I just want to move on with things.” And the reverse is true, patients where you think that they would actually prefer an ileal conduit and like, “You know what, I really want the neobladder. I’m willing to put the time and effort that goes into doing that because it’s important for me to have that component of my quality of life.”

Dr. Ashish Kamat:

Same thing with sexual function. I tried to spare nerves and every patient, unless it’s going to compromise their cancer care. And that’s a discussion I have with the patient upfront, but patients need to be aware of all of this when they’re having the discussion and going into a radical cystectomy. All the advances we have nowadays, you’re a prime example of that, but the patients should expect to love as close to normal a life as they are used to after radical cystectomy, as they did before radical cystectomy.

Dr. Ashish Kamat:

And again, I have many examples, one that I’m really proud of as my patient, and I’m not going to mention her name, even though she’s asked me to, and she’s been in the news. She’s 19 years old now at a very rare, unusual type of bladder cancer that required her to undergo a radical cystectomy at the age of 17 ish. And she didn’t want, and also was not a candidate for a neobladder, chose a stoma, and then a year and a half after her surgery ended up getting a soccer scholarship to a major university in the country and plays on their team. So quality of life is something that is very important for us to provide our patients. And it’s very important for me, I think for our patients to be a partner in that discussion from day one.

Rick Bangs:

Yeah, that’s an amazing story and I hadn’t heard that one before. And so clearly getting information is really critical. And then you’ve pointed out BCAN has some really exceptional resources and can connect people with other patients that can talk through the day to day. So getting information to avoid that buyer’s remorse is, I think there were the critical solution there. At what point would you urge a patient with non-muscle invasive bladder cancer to go ahead and get the radical cystectomy? What would be the criteria that you and the patient would use to decide?

Dr. Ashish Kamat:

So there’s a simple way to go about that. And I look at it in my discussions with my patients as the following, we want to move away from trying to save the bladder when not doing so will present us with the loss of the opportunity for long-term cure, right? So I will allow my patients to try and save their bladder with multiple therapies so long as it’s not foolish. So as long as it’s not something I wouldn’t allow someone in my family to do. But as soon as that occurs where any more attempts of trying to save the bladder is risking my patient’s life at that point, I will say, no, we should move to radical cystectomy. And when is that? So that is when you have either a very, very aggressive disease that is still non-invasive, right? So the greatest, very aggressive, but the stage is non-invasive.

Dr. Ashish Kamat:

But we know from data on tens of thousands of patients, statistically speaking that patients that have very deep T1 disease, plus CIS, plus micro papillary, maybe some small cell, all of these variants thrown in, their likelihood of metastasizing while they are trying to save their bladder with BCG or something else is very high. So those patients should initially upfront be considering more definitive therapy, either radical cystectomy or in some situations of radiation therapy is appropriate, but something other than intra vesical therapy. And when a patient has been successfully treated with intra vesical therapy and has either had initial response or the treatment has failed, those patients also then are moving along the path where their tumor is trying to tell us that they’re not as what they see, even though the majority of these patients may have responded to BCG, for example.

Dr. Ashish Kamat:

If a particular patient’s tumor doesn’t respond, that tumor is progressing along a different pathway. It doesn’t mean they have to go to radical cystectomy right away, they can try other treatments, but beyond a certain time that the tumors are just recurring constantly, the time to pull the trigger on more definitive treatment, that’s before there’s any metastatic disease. Because as you know, once bladder cancer metastasizes cure is still in the minority of patients.

Rick Bangs:

Yeah. We still have to make some progress in that category, obviously. So that leads to an obvious question which is, what does the future look like for patients on the slippery slope?

Dr. Ashish Kamat:

Well, I think the slippery slope is gaining more traction. It’s not as slippery as it used to be. And I think it’s because of several things. Number one, we have better understanding of tumor biology in general. Number two, we have better tools with which to understand what we understand, but also importantly to recognize what we don’t know. And if you don’t know something, it’s perfectly fine to have a frank discussion with the patient and say your tumor is something that we don’t understand. A little more aggressive treatment might actually be safer for you. We have better tools to resect tumors. We have better tools with which to treat patients. The radical cystectomy that you mentioned is getting to a point where patients now, at least at our center are in the hospital three, four days and are ready to go home as opposed to 10 days.

Dr. Ashish Kamat:

And previously when they still felt lousy after surgery. And of course, recognizing that not all patients may need a radical cystectomy. Some can go on to get salvage treatment. There’s an approved drug pembrolizumab, and vergene is currently being looked at by the FDA for fingers crossed potential improvement, many others as well. And of course, radiation therapy in the well selected, appropriate patient. We can still save their bladder and not have to remove it and provide them with multimodal trimodal therapy. So there’s a lot more options. And I think the slippery slope is well-deserving of the fear that you alluded to that people should have a foot, but I think with the right partners on our side and your side and just with the whole beacon community coming together, I think that slippery slope is hopefully not going to be as slippery for most patients.

Rick Bangs:

Yeah. I think the partnership is so critical. Dr. Kamat, thank you for coming back and helping us understand the risks around the slippery slope. I know our listeners are going to appreciate this and it will help them make decisions.

Dr. Ashish Kamat:

Always a pleasure.

Rick Bangs:

In case people want to get in touch with you, and I know you shared this information in our previous podcast. Could you share your Twitter handle or any other information that you’d like people to have?

Dr. Ashish Kamat:

Sure. My Twitter handle is U-R-O-D-O-C-A-S edge, but I’ve found that actually what has worked really well is when they just contact BCAN and then I’ve received queries from BCAN’s support team and things like that. So I’m happy to help in whatever way works best, but if you want to do it through BCAN, that has really worked well and streamlined things for patients in the past, I think.

Rick Bangs:

That’s great. Thanks so much for this information. Just a reminder. If you’d like 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. Thank you for listening and we’ll be back soon with another interesting episode of bladder cancer matters. Thanks again, Dr. Kamat.

Voice over:

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 B-C-A-N.org.