Transcript of The Pluses and Minuses of Cystoscopies, TURBT and Other Diagnostic Tools with Dr. Alexander Kutikov

July 28, 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 BCAN.org.

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 of the bladder cancer efficacy network, or as many call it, BCAN, producers of this podcast.

This is podcast is sponsored by Merck and FerGene. I’m excited to have Dr. Alexander Kutikov, chief of urology at Fox Chase Cancer Center in Philadelphia as our guest today. Dr. Kutikov, I’m really excited about talking about the challenges of judging how far a patient’s bladder cancer has progressed.

Dr. Alexander Kutikov:         

Yes, it’s a very important topic and it comes up in clinical practice quite routinely, and some critical pivotal clinical decisions stem from sort of the uncertainty that surrounds that particular issue.

Rick Bangs:    

Okay, so let’s kind of walk through the life cycle here from a patient point of view. One of the first things that a patient is going to be when they’re diagnosed is the stage of the bladder cancer. That describes how far the bladder cancer has progressed, and less is clearly better here. So as a urologist, you first estimate the stage during cystoscopy and so what does the cystoscopy actually tell you?

Dr. Alexander Kutikov:         

Right, so this is actually quite confusing in bladder cancer. Staging is, unlike for some other cancers, is not very clear cut. I’ll sort of try to explain why. So generally, staging for most cancers is divided into two parts. One is clinical staging and one is pathologic staging. Now what does that mean? Clinical staging is staging that’s determined from CAT scans, from scans and from the clinical presentation of patients in general. Pathologic staging is determined from resection of a particular cancerous tumor.

So, you can have one stage as your clinical stage and then your pathologic stage can be either the same or it can go up or it can go down. Bladder cancer is particularly challenging where in the clinical part of the staging there are sort of various phases of how a person is staged. Why is that? Because just of the nature of bladder cancer. So to walk folks through that, people come in and they may have blood in their urine and they may get a CAT scan first, and so you have that piece of information. Then, they may have an office cystoscopy and then you have that piece of information.

And from those two pieces of information we can get some staging data, but it’s often not fully definitive. And then we have what’s called the transurethral resection of bladder tumor or TURBT, and a TURBT we actually scrape the tumor and get pathological assessment of how deep into the bladder wall the tumor has gone. And so, that’s still all considered clinical staging although, as you can see, it’s very different than from most tumors. Now, pathologic staging in bladder cancer is obtained when the bladder is removed, which doesn’t happen in the vast majority of folks with bladder cancer.

Rick Bangs:    

Okay, so there’s some progression here. But if you use blue light cystoscopy do you get better results from that part of the process?

Dr. Alexander Kutikov:         

Right, so blue light cystoscopy is this really quite marvelous technology that allows you to put a tracer into the bladder that is preferentially concentrated in cancer cells but not in healthy cells. Basically, cancer cells lose their ability to pump out this tracer so under a different wave length of light, the tumors show up as pink to the urologist when they’re assessing the bladder. So, what blue light cystoscopy allows you to do is, it allows you to see tumors that are maybe difficult to see in white light in regular cystoscopy.

So, it allows you to sort of get a cleaner slate when you’re resecting and treating non-muscle invasive bladder cancer. Whether blue light cystoscopy actually allows you to better stage, and let’s pause for a second here and let me just walk folks through kind of what staging… give a little bit more details about staging. All these tumors in the bladder, they start in the inner lining of the bladder. It’s like the inner lining of your cheek. Okay? And they come in two varieties.

They come in high grade and they come in low grade. And that’s called grade, it’s different from stage which sometimes is confusing. Grade is a determination by pathology under the microscope on seeing how aggressive the cells look. It doesn’t tell you how deep in the wall they go. How deep in the wall they go, that’s stage. And so, you can have a stage where it’s still in the mucosa, it still hasn’t penetrated any of the lining, and that’s either TA or carcinoma in situ.

Another point of confusion in bladder cancer where there are some tumors that are called TA tumors and some tumors that are called carcinoma in situ. And without sort of delving into the details on that, these are basically tumors that are right on the surface. Then there is T1, which is tumors that penetrate into the first layer of lining under the mucosa, which is called the lamina propria, but basically it’s tumors that are invasive but are not muscle invasive. They haven’t got into the true muscle of the bladder.

Those are stage one tumors, T1. Then T2 tumors are ones that penetrate into the muscle of the bladder. Now, whether blue light cystoscopy allows you to better predict muscle invasion is sort of orthogonal to what blue light cystoscopy does. In other words, that’s not what its purpose is. It’s purpose is to help you find tumors on the surface and then to scrape them and then a pathologist determines the depth of invasion. If that makes sense?

Rick Bangs:    

Yeah, that does. So, there was an article you recently co-authored that talked about the limitations of this cystoscopy, this visual inspection, and some limitations regarding how urologists try to estimate how far the cancer has progressed. Tell us about the study and also what you personally believed before the study and what you came to understand after the study was completed.

Dr. Alexander Kutikov:         

Right. So, this study was a bit of a journey, and interrupt me if I need to clarify anything, but let me just start from sort of the beginning on why we did this study and what questions we were trying to answer. So when folks have muscle invasive bladder cancer, when tumors have penetrated the muscle of the bladder, we know that that’s a gateway to progression. That’s a gateway to bladder cancer spreading to the lymph nodes and to spreading to other parts of the body. So, the gold standard recommendation is to get chemotherapy, which is called neoadjuvant chemotherapy which means before surgery, and then get surgery which is removal of the bladder and then a urinary diversion.

What we know is that about 30% of people who get neoadjuvant chemotherapy and then go on to have their bladders taken out actually don’t have any evidence of cancer in their bladder upon removal, which we usually celebrate and say that the prognosis is excellent. The rates of recurrence are on the order of no higher than 10% in those folks. And we say this was necessary to do and then we move on and patients usually do quite well.

But another way to look at this is that this is really an untapped opportunity. There are 30% of people who get chemotherapy before bladder removal who may be able to keep their bladders. However, there are multiple reports throughout the years, and really this general dogma in the field, that you cannot predict these PT0 bladders. PT0 means pathologic T0, so you have no cancer at cystectomy. You cannot predict these PT0 bladders accurately because after chemotherapy… and remember, the way we diagnosed their muscle invasive disease, we already scraped these tumors. Right?

So, we scrape these tumors and if you scrape a tumor and remove some of the bladder without chemotherapy, they actually have a 15% chance of not having any cancer left in their bladder. So, these people’s tumors were scraped and then they get chemotherapy and then they are undergoing bladder removal. And again, there was this really sense in the field with some retrospective data supporting it, that you’re really going to miss some people who have bladder cancer under the surface, under the inner lining of the bladder.

And cystoscopy in those folks would look like you walking into a room and looking at the walls, and looking at the wallpaper looking just fine, but in the wall itself there is cancer. So, the bladder puts up a new lining over the previous tumor site, it looks good and then you basically say, “Hey, you have nothing in your bladder,” but you miss a certain number of people. And what number of people you actually miss, what percentage of people whose bladders look completely clean on cystoscopy, but then if you took out their bladders they still have bladder cancer under the surface, was a point of contention.

I personally, when I set out to study this, I thought we were overestimating the percentage of tumors that were actually what’s called submucosal, that were under the surface. Now Rick, stop me if this is too confusing, if there is anything to clarify.

Rick Bangs:    

No, I think what you’re really helping us understand is that there’s limitations based on what you can look at, so your analogy of the wallpaper, right, so we don’t know if there’s rot under there or whatever. And so, there’s some constraints around that. We certainly want there to be no evidence of a tumor, but visually there’s only so far you can go.

Dr. Alexander Kutikov:         

That’s exactly right. That’s exactly right. So the question I wanted to answer is, what is the true negative predictive value? How much can we trust a scope that is negative? My hypothesis was that if you really set up a program where you systematically evaluate the bladder, and then you biopsy and scrape the previous scars and you really are methodical about it, that you could actually drive down this miss-rate of submucosal tumors, of tumors that are deeper than that wallpaper, to something that is acceptable.

And then, all of a sudden you open a path to these 30% of patients who have clean bladders upon bladder removal to actually enroll them into trials and try to save their bladders. So the way to study this, and it had actually not been done, was to ask patients who were going to have their bladders removed to volunteer as part of a clinical trial to have us quickly look in their bladders and do this mapping. Okay? Right before bladder removal.

And then, remove their bladders regardless of what we saw. These bladders were being removed anyway as per the standard of care, and we were basically, as we were doing this, we’re going to grab this information in order to help patients down the road. And so, we did this trial and it reached what we call futility quite quickly with about 70 patients, where we saw that our miss-rate for missing muscle invasive bladder cancer on these very systemic endoscopic, cystoscopic, evaluations was about 25%. So, in 25% of people in who we were as sure as we can possibly be that there was nothing in the bladder actually ended up having muscle invasive bladder cancer once their bladder was removed.

So, it was a very sobering finding, but an important one because it really outlines the challenge in our field of what we need to figure out. We need to figure out how we can accurately diagnose out of the folks who really have no evidence of cancer in their bladder after neoadjuvant chemotherapy, how can we pick up that quarter folks whose tumors are wolves in sheep’s clothing so to speak? Their bladders look clean but there is an aggressive cancer deeper in. There is lots of sort of work being done in trying to figure out that problem. This trial, at least to me, really identified this problem and defined it in a way that helps us understand it.

Rick Bangs:    

25% is a lot of people, so obviously we’ve got to do something to make it better. So, what might you learn from a CT scan or some of the other imaging that you would do that might supplement what you would have uncovered during the cystoscopy?

Dr. Alexander Kutikov:         

Yeah, so a great question and an important one as well. So, how can imaging help you? Imaging in bladder cancer folks is also very challenging because once you’ve scraped the bladder, the scar at the scraping site really can mimic a tumor. On the other hand, imaging is not sensitive enough. It can sometimes not be able to pick up a tumor that’s hiding in the wall. Now, there’s been a lot of progress in imaging in studies from the UK with MRI where folks are getting MRIs before they ever got a TURBT, before they ever got a transurethral resection of the bladder. And there, there is some evidence now that you can actually have quite good predictive ability in diagnosing muscle invasion versus no muscle invasion.

But the challenge really remains in folks who’ve already had a TURBT because they have the scar, they get this edema which is this swelling at the area of resection, and we don’t quite an imaging modality that helps us clinically where we can kind of hang our clinical hat on the imaging findings. Just to speak a little bit more on imaging, people ask, “Why can’t I get a PET scan to see if I have muscle invasion or not?” Remember, a lot of these positron emission tomography PET scan tracers are excreted in the urine, so there’s such high uptake in the urine that it basically makes interpretation of the bladder wall very difficult because urine lights up so bright. So, there’s inherent challenges to imaging bladder cancer that there’s a lot of groups that are trying to work to overcome them, but clinically we’re not there yet.

Rick Bangs:    

Yeah, so a lot of challenges here that aren’t necessarily seen in some other cancers. It sounded like MRIs seemed to be directionally promising but it has to be done before the TURBT and more studies would have to be done.

Dr. Alexander Kutikov:         

Yeah, I mean to be fair, there are some studies that are showing some promise in post-TURBT settings, but still this is still ongoing work.

Rick Bangs:    

Okay. All right, so let’s go back to that TURBT, which is the surgery which is done under anesthesia and it’s removing the tumor. So, what additional information are you getting from that, that you didn’t get from the imaging as well as the cystoscopy that is a visual examination?

Dr. Alexander Kutikov:         

Right. So, one of the things to determine is to make sure that there’s a deep resection, that the resection is deep enough to obtain the muscularis propria, the muscle. Okay? That’s sort of priority number one. Priority number two is to figure out what kind of disease is in the bladder. Is it multi-focal? Is there more than one tumor? Is there presence of carcinoma in situ, which is these aggressive flat tumors that really up the risk of progression in certain patients? The other important piece of information on pathology, when the pathologists look under the microscope, is lymphovascular invasion, another big risk factor.

I also want to know whether the tumor is in the diverticulum or not, which are these out-pouchings in the bladder, because tumors in diverticula can progress more quickly because the lining is thinner. Is the tumor blocking the kidney? Is there hydronephrosis? Usually that’s obtained from the CAT scans that are done before TURBT, but sometimes it’s a little bit hard to tell how the tumor is related to what’s called the ureteral orifice, which is this rice grain sized little opening that allows drainage of the kidney and the ureter into the bladder.

We look for varied histologies, which is a fancy way of saying is this bladder cancer, does it have another pattern under the microscope that makes it higher risk, things like micropapillary or plasmacytoid, those are words that we use to risk stratify folks further. Is there carcinoma in the prostatic urethra which also adds additional risk? So, there’s a lot of information that a urologic oncologist who’s experienced in bladder cancer is looking for during the TURBT.

And why is this important? This is important not only for folks who have muscle invasive bladder cancer, but it’s also very important in folks who have high risk non-muscle invasive bladder cancer. One of the biggest challenges in bladder cancer are patients with high grade T1. Remember I told you that some of these tumors go into the first lining, into that lamina propria? Those T1 cancers? Those T1 cancers really need to be handled with kid gloves. Those cancers can progress under one’s nose. A high percentage of those patients who may require cystectomies down the road, so those patients need to be monitored carefully.

And what’s really, really important that sometimes, unfortunately, is not done routinely is that if somebody’s diagnosed with a T1, with a bladder cancer that’s invading the lamina propria, that a re-resection is done. And what does that mean? That means in three to six weeks somebody goes back in and re-scrapes that scar, allows the scar to pull in and basically re-scrapes that scar. And why is that important? Because no matter how good of a resection somebody did at the onset, there is a 45 to 75% chance that patient will exhibit residual tumor cells. Okay?

And there’s up to a 40% chance that those patients whom we thought were T1 would turn out to be T2, which have muscle invasion. So, it’s very important for basically therapeutic purposes for treating patients along this journey, but also for appropriately diagnosing T2, a muscle invasive disease, that a re-resection is done. And also, a re-resection can be used as a prognosticator. If there is residual, sort of substantial residual disease at re-resection, those patients have a higher risk of disease progression, those patients that had clean bladders on re-resection.

So, re-resection is very, very important for patients with that T1 disease and I cannot over emphasize that more. I really sort of encourage the BCAN community to… especially those… I send patients to the message boards all the time because it’s such a greatly curated and such a helpful resource for our patients. But this T1 re-resection, it’s very important for the patient community to be aware of it and to make sure that it’s done, because it’s absolutely mandatory.

Rick Bangs:    

Yeah, we spent a whole podcast on what was described as the slippery slope, which is this T1, stage one, with high grade and how you kind of manage that. I mean, I think you’ve reinforced some of the challenges with that here. I’m sure our listeners are a little bit curious about something, and I know there’s risk involved here, so the more tumor you get… and obviously you want to get it all… but the deeper you scrape the more likely you would be to get more tumor out. So, why wouldn’t you just continue to scrape deeper in patients?

Dr. Alexander Kutikov:         

Yes, it’s a great question and as you say, you hit the nail on the head. It’s a risk balance. I teach residents, we’re at a cancer center, we do some of the biggest surgeries that are done in surgery, but I tell them a TURBT is arguably one of the most important surgeries that one needs to master because it really determines patient’s destinies. It has to be done well. It’s easy to harm a patient with a TURBT and it’s easy to not get enough diagnostic tissue. So, this is a balance where you want to get muscle but you don’t want to perforate. You don’t want to go through the wall because perforation carries its own significant risks both immediately and long term.

So, transurethral resection requires experience and it allows a comfort level and there are some… people who don’t treat bladder cancer a lot, they may not have that comfort level and that’s why a lot of the specimens that are obtained out there don’t have muscle in the specimen. People didn’t go deep enough because they’re trying to be safe. Which is fine, it’s just then somebody needs to seek another opinion with somebody who is very comfortable with these sort of procedures and perform a completion transurethral resection of bladder tumor, and sometimes in those instances you kind of count that second TURBT at a tertiary referral center as your first TURBT because this is the first time we actually got you completely clean and then you need another re-resection.

So, sometimes it’s sort of a series of these re-resections in order to make sure that we’re all comfortable to proceed with intravesical therapy, which is putting medicine in the bladder, things like BCG, which is kind of our main workhorse. And BCG only works if the bladder is clean. If there is residual tumor BCG will not get rid of it. So, it’s very important to have a clean slate. And this is where blue light comes in and helps somebody get a clean slate.

Rick Bangs:    

Okay, let’s talk a little bit about something you hinted at before, which is this clinical versus pathological staging of the tumor. So, you’ve got the cystoscopy as an input, you’ve got your imaging as an input, and you’ve got this very difficult surgery called a TURBT, which I think as patients we kind of assume is relatively simple but as you’ve pointed out and I’ve heard some of your counterpoints say, it’s a very tricky surgery and it needs to be done really well.

So, if we’ve got this data from the clinical side, it could vary from what would happen when the bladder is actually removed, right, the pathological staging? So could you talk a little bit more about that, and talk a little bit about something you suggested previously which was node involvement, lymph node involvement?

Dr. Alexander Kutikov:         

Yeah. So, staging from TURBT is not perfect, even in the best of hands. We know that when we take patients with stage one, T1 tumors, and we offer them early cystectomies… so sometimes they’re robust young patients with bladder cancer that just looks aggressive. It’s not muscle invasive yet, and it may be multi-focal, it may have carcinoma in situ associated with it, it sort of has high risk features, and after a discussion the treatment team and the patient and family decide to say, “Okay, let’s just go forward with an early cystectomy.” And their cystectomy is basically a cystectomy that is done before muscle invasion occurs. Here we know that, depending on the series, but approximately 30% of patients that had an early cystectomy will actually have muscle invasive disease where we basically did not make the diagnosis on TURBT, and really dovetails with that data from that PT0 trial that I described to you where the assessment of tumor status from inside the bladder is just not perfect.

We work within these limitations, I mean, medicine… we can only try to minimize uncertainty, there’s not way to eliminate it. Usually in those situations with grade T1 disease we’d go on to early cystectomy at most centers not that frequently because we know that giving one round of BCG with newly identified T1 disease is sort of the traditional approach, and that progression within the first six months of this diagnosis is rare. It’s on the order of less than 5%, sort of 4% gets thrown around sometimes. So, we generally try BCG. But cystoscopy always has to be remembered that, cystoscopy and TURBT, we have to remember that we may be missing some disease and that’s why it’s very important to just watch patients quite closely. Now, did I answer your question or was there another part to this question?

Rick Bangs:    

I think I want to talk a little bit more about the tumor versus the cancer, which you’re very nicely segue-waying into here.

Dr. Alexander Kutikov:         

All right, the lymph nodes, right. So yeah, progression, what does progression mean? So, progression means the tumor that started in the inner lining of the bladder, go deeper into the bladder, and generally it goes to T1 and then it goes to T2 and then it skips to lymph nodes, and then it can go to other parts of the body. With these T1 tumors, sometimes they skip the T2 stage and they actually progress into lymph nodes without us being able to detect muscle invasion. It’s rare but it can happen. How do we diagnose lymph node invasion? How do we diagnose metastatic disease in other sites of the body? That’s really done on imaging.

Usually cross-sectional imagine with CAT scans or MRIs is enough, and PET scans are used… unlike in lung cancer where PET scans are used in just about every patient… PET scans in bladder cancer patients are used selectively. And there are some opinions and caveats about it because sometimes after TURBT you can have some inflammation in the pelvis and some of the lymph nodes can take up that sugar from a PET scan and actually light up in absence of cancer. So, sometimes you can get a false positive from a PET scan. So, we’re a little bit careful of getting these PET scans right around the time of a TURBT.

Usually you can diagnose the abnormal lymph nodes just on CAT scans and MRIs alone. It’s important to get imaging of the chest where one of the main sites for bladder cancer is metastasis to the lungs and generally most patients with T1 and T2 get baseline chest imaging in order to compare to later on in the bladder cancer journey and make sure that there are no changes. Because sometimes people do have little nodules that are completely unrelated to bladder cancer that just need to be monitored. So, if I’m answering your question, it’s really imaging that drives identification of lymph node spread and of spread to other sites of the body.

Rick Bangs:    

Yeah, so like the actual staging of the tumor, there’s limitations on the imaging side as well both in terms of false positives, you think there’s a cancer but there really isn’t. Or, you don’t think there’s cancer but there really is. Right?

Dr. Alexander Kutikov:         

Yes, absolutely. Again, it comes up in clinical practice quite frequently where somebody is going for bladder removal and the scans don’t suggest any spread, and then the surgeons take out the lymph nodes and the lymph nodes have some cancer in them. So basically, the lymph nodes had some cancer but the cancer hadn’t grown, it wasn’t plump enough to actually show up on the scans.

Rick Bangs:    

Yeah, so I want to get back to the neoadjuvant chemotherapy, which is an attempt to get rid of the cancer, and I’m differentiating that from the tumor. So, the way I explain it to my fellow patients is, the tumor is like a beehive. It’s like a home for the cancer. If it’s high grade cancer these are like angry, nasty bees, and they may not all be in the hive, right, which is the tumor, the home. And so, part of the logic, as I understand it, and you can help me confirm, but part of the logic for patients getting neoadjuvant chemotherapy even if we think that the cancer has been staged down, is that these angry bees are looking for a new home and we want to kill all the angry bees before we remove the bladder. Does that make sense?

Dr. Alexander Kutikov:         

It’s a great analogy. It’s absolutely exactly how we think about neoadjuvant chemotherapy and it’s deliverables. But also, just to take that analogy even a little further, there’s probably always a few bees that are flying around, it’s just most of those bees, or even all of them, have not gained the mutation, have not gained the ability to actually form a new hive somewhere else. So, they’re kind of out there and they just disappear, they die out in the peripheral of the body. And it’s really this ability to implant into other tissues and grow outside of the bladder in other tissues where those are the cancers that are problematic and those are the cancers that you’re really trying to get rid of with neoadjuvant chemotherapy before you go to surgery. And also, surgery… it makes the beehive, the original beehive to use your analogy, it makes it smaller and it makes surgery more effective.

Rick Bangs:    

Right. Okay, so we know some patients are going to be reluctant to wait to have that chemo. I know when I was pre-cystectomy just getting that cystectomy done was really, really important. I wanted it done yesterday. But there’s also some folks that are going to refuse to have a cystectomy because they mistakenly believe that this TURBT, which theoretically removed the tumor, therefore maybe my cancer has been removed. But given what we’ve just talked about, that doesn’t make sense. That’s not a logical conclusion to draw as a patient.

Dr. Alexander Kutikov:         

Right. I mean, there’s sort of a lot of complexity here as well. So let’s talk about timing of cystectomy, and then we’ll talk about sort of if the tumor was removed… because there’s another layer here… there’s another option, there’s radiation therapy. Patients need to be aware of that, that’s a really good tool for the right patient. But let’s talk about timing. So, historically there was this big debate about neoadjuvant chemotherapy. The medical oncologists said, “Hey listen, you take out people’s bladders and 30 to 40% of them actually recur at some point in the first five years. You’ve got to have some better tools here, and let’s use two hammers to hit these tumors. Let’s use chemotherapy and then surgery.” The surgeons, on the other hand, said, “Well listen, I hear you but you may be doing harm here because you’re delaying the treatment that is definitive, which is surgery, because not all patients actually respond to chemotherapy.”

There was a prospective randomized trial done by Dr. Grossman and published in The New England Journal in ’03 that showed definitively that when you randomize people, when you basically enroll people into a trial and you have half of them walk through a door that goes directly to surgery and the other half of them walk through a door that gives them chemotherapy and then surgery, that there is a benefit to having chemotherapy and surgery. Okay? But still, there was again this debate that it just took too long to give chemotherapy and you delayed definitive treatment from patients.

So, the traction on neoadjuvant chemotherapy was far from 100%. I mean, even recently our National Cancer Database studies show us that only about 30% of patients that have their bladder removed get neoadjuvant chemotherapy. And again, it’s sort of the sentiment that these patients are older, they won’t be able to tolerate both, just use the one that works best which is surgery. There’s sort of a lot of what I call excuses for not giving neoadjuvant chemotherapy.

But what we’ve done at our center and what is really is being utilized at many centers now, are these dose dense regimens of chemotherapy. One of the seminal studies was published by my medical oncology colleagues, Dr. Plimack, who ran the study here at Fox Chase almost 10 years ago now, where you can basically give chemotherapy as a six week course. In reality, in four weeks you get all your chemotherapy. It’s three sessions. It’s day zero, week two and week four. Those are the three cycles of dose dense impact, and then you give two more weeks for the chemotherapy to wash out, that’s why it’s called a six week course.

And then, four weeks later you go to surgery. You sort of allow the patients to get wind back in their sails and then you go to surgery. So, from the day the first chemotherapy hits one’s veins to surgery is 10 weeks, so there’s not much of a delay at all. Actually, in a busy surgical practice it’s difficult to schedule an epic surgery like this much sooner because it’s sort of a lengthy procedure and in a busy center that’s just how the surgical schedules work. So, you’re actually not losing much as far as time delay. So, there’s that. So those dense regimens, in my opinion, have sort of resolved this big debate about delays because there’s not much of a delay.

Now, what about saying okay, the TURBT has cured all my cancer and, like you said, and sort of the data I talked to you about, 25%, we know that even if your bladder looks perfect there’s still some disease there. What about radiation? Is that the right option? I encourage most of my patients to discuss with our radiation oncologist the deliverables of radiation. There are strong opinions about pros and cons of radiation but it is an absolute tool for the patients who are incredibly motivated to keep their bladder, who for instance have only a solitary T2 tumor and don’t have associated sort of multi-focal disease, or for patients who are really elderly, frail, and are just not cystectomy candidates.

And so, this is sort of a lengthy discussion about pros and cons of radiation, but we have to remember that radiation will treat that cancer right now, but there’s always, as we know, bladder cancers recurring so there is a lifetime of commitment here that’s important to make sure that we are following the patient very closely and making sure that new tumors don’t develop. And when they do develop, we treat them. Radiation can affect the function of the bladder, although if it’s done at an experienced center the bladders usually work quite well. So, radiation is also definitely an option that the patient needs to understand and potentially consider.

Rick Bangs:    

Yeah, I think there’s a lot to consider here. We’ve discussed some of what our capabilities are in the year 2021. So, get out your crystal ball and tell us a little bit what you believe the future might bring us that’s going to help us reduce a lot of this uncertainty.

Dr. Alexander Kutikov:         

Yeah. So, as far as making cystoscopy a better predictor of aggressive and muscle invasive disease, where I see the puck is moving is, there’s imaging, there’s that imaging where we may kind of crack this nut and figure out imagine features that are very predictive. I think what’s more encouraging is the progress that’s being done with biomarkers, and being able to use sequencing data from serum from urine. For instance, there’s circulating tumor DNA technology that really is probably going to give us a bit of a window into what’s happening in the body outside of our view from the cystoscope, and to letting us know really on a molecular level if there are tumor cells that are floating around.So, I think there’s a lot of hope there in the next decade.

Rick Bangs:    

That’s great to hear. And so, as we kind of close here, we’ve talked about what I refer to as a slippery slope, these stage one high grade bladder cancers, in a previous podcast, and you’ve given us an even deeper understanding of not just that particular diagnosis but others. So, can you can of summarize your parting advice for patients who want to navigate these uncertainties of high grade bladder cancer and get the best results they possibly can.

Dr. Alexander Kutikov:         

Yeah, this is a very dynamic and complex space. It’s constantly changing. I think it is important to partner with your local urologist because there is really a lot of care that needs to happen on a routine non-delayed fashion. But also, seek another opinion at a tertiary referral center or cancer center to make sure somebody reviews your records and weighs in on the opinion regarding your disease, somebody who really specializes in bladder cancer and who really knows what’s happening in the field, understands the trials that you may be eligible for, understands the new agents that are continually coming out. So, I think there’s a lot to be said about getting a couple of opinions when you receive this diagnosis. Patients always sort of communicate that they’re worried that their relationship with their treating physician will be damaged by a second opinion, I’ll tell you that is really not the case. Physicians understand that second opinions are important. They get it for their own family members.

There is lots of perspectives on the same issue. I always tell patients, you buy a new HVAC system you get four estimates. You get four contractors. Why would you not get a couple of people to look at your cancer?

Rick Bangs:    

Oh, absolutely. We could do a whole podcast on second opinions, which I think to your point are so important. I’ve never talked to a patient who told me they regretted that they had gotten a second opinion. I think you’re spot on there. All right, I want to thank you Dr. Kutikov for sharing your research and your results. I know our listeners are better informed about the uncertainties of the progression of bladder cancer and they’re in a better decision to make a shared decision with their urologist as a result.

Dr. Alexander Kutikov:         

Thank you, Rick, and thank you for doing this very, very important work. This is, again, so complex and educating the patient community there is just… it’s critical. And thank you BCAN for continuing to do what they do. Really this is a tremendous organization that’s grown over the years and I see my patients benefit from it really every day.

Rick Bangs:    

Yeah, that’s great to hear. So, in case people would like to get in touch with you, could you share your Twitter handle so that people could connect with you?

Dr. Alexander Kutikov:         

Sure yeah, I usually don’t answer kind of particular clinical questions over Twitter, but you can follow me at @Uretericbud, that’s the kind of empirical origin of the kidneys, so it’s Uretericbud on Twitter. I do sort of try to post the latest studies in urologic cancers. You can always ping me there and I’m glad to sort of connect. But questions about a particular case are best done in a consultation and we do telemedicine these days so that’s easy.

Rick Bangs:     Could you spell Uretericbud?

Dr. Alexander Kutikov:         

Yeah, so it’s @ U-R-E-T-E-R-I-C-B-U-D. This was back in the days when there was AOL where everybody was buddy, right, you had a buddy. So, this is Uretericbud. So yeah, U-R-E-T-E-R-I-C-B-U-D.

Rick Bangs:    

Great, thank you so much. 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. Thanks for listening and we’ll be back soon with another interesting episode of Bladder Cancer Matters.

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 BCAN.org.