Understanding Non Muscle Invasive Bladder Cancer (NMIBC)

With Dr. Amy Luckenbaugh

You can read the entire Understanding Non Muscle Invasive Bladder Cancer webinar transcript at the bottom of this page.

Year: 2021


Part 1: Understanding Types and Stages of Non Muscle Invasive Bladder Cancer

Video (15 min) | Transcript (PDF)


Part 2: Understanding Treatments for Non Muscle Invasive Bladder Cancer

Video (16 min) | Transcript (PDF)


Part 3: Question and Answer about Non Muscle Invasive Bladder Cancer

Video (25 min) | Transcript (PDF)


Full Transcript

Stephanie Chisolm:

Welcome to understanding non muscle invasive bladder cancer, a patient insight webinar from the Bladder Cancer Advocacy Network.

A bladder cancer diagnosis can be terrifying to a patient and their family. What do you need to know about non muscle invasive disease in terms of understanding your diagnosis and your treatment options? Tonight we’re really delighted to have urologist, Dr. Amy Luckenbaugh, Assistant Professor at Vanderbilt University Medical Center. Dr. Luckenbaugh is a surgeon whose clinical focus centers around the comprehensive care of patients with urologic malignancies like bladder cancer. She currently serves as a member of the Society of Women in Urology board. And through her research, she really aims to better understand new options for treating bladder cancer patients.

Really delighted that Dr. Luckenbaugh is here with us. She was one of our 2019 John Quale Travel Fellows, and was able to attend our 2019 Bladder Cancer Think Tank, and be introduced to the community. So it’s lovely to have you here, Dr. Luckenbaugh. If you would like to share your slides, you can take it away right now. I’ll stop my share.

Dr. Amy Luckenbaugh:

Great. Thank you so much. And thank you so much for having me. So I have no disclosures that are relevant to this talk. And I’m going to try to cover a lot of information, and leave about 15, 20 minutes for questions at the end. And this is kind of the outline of where we’ll be going. About the background, diagnosis and evaluation of non muscle invasive bladder cancer, staging, what it means, the different risk groups and why they’re important, and various treatments, as well as emerging therapies.

So, bladder cancer in the United States, there’s about 80,000 new cases per year. It’s the fourth most common malignancy in the United States among men, and it is not in the top 10 for cancers among women. Risk factors as we know are… Smoking is the number one risk factor, and number one modifiable risk factor for patients to know.

Bladder cancer is the eighth most common cause of death in men. But I think it’s important and encouraging to know that most of the cases we find are non-muscle invasive at diagnosis. So, 70% of them are non muscle invasive bladder cancer, and that’s very important, and it kind of allows us an area to treat and hopefully prevent them from becoming muscle invasive. 20% are muscle invasive at diagnosis. And 10% present with disease outside the bladder. So, that is just a brief background.

And how about diagnosis and evaluation? So, the way this is often diagnosed is people can present with blood in their urine. And anytime we see blood in the urine, we should be looking inside the bladder with a camera that we put in through the tube that you pee out of. And then if there is a tumor, it is our job to resect the entire tumor and perform upper tract imaging. And what upper tract imaging means is a CT scan to look at the kidneys, the ureter tubes as well. Because those tubes are lined with the same type of cells that the bladder is lined with. And so, it’s important to make sure that there’s no cancer in that entire tract.

Dr. Amy Luckenbaugh:

And then there are some rare cases where we do these cystoscopies and everything looks normal, but we send cells off from the urine, and it can show up as having cancer cells in the urine, and we could not have seen something. When we see that, there are some other places we have to try to look. In a man, that’s in the urethra tube that you pee out of, that’s in the prostate, as well as up in the kidney and ureter tubes. And when we have those instances where we might have abnormal cells that we see in the urine, but a normal bladder, we sometimes do something called a blue light, or enhanced cystoscopy.

And what that does is we place a catheter, and we put a small amount of medicine in your bladder, we ask that you hold it for 30 minutes, and then we take you to the operating room and look under a special light. And you can see here in the photos of what a tumor under normal light might look like, right here. And then under that special light, what it might look like. And so, it can be challenging to see some of these, and this can add to some utility and help diagnose things. There were some early thought that this might reduce recurrences about one year afterwards, because you can make sure to see things you may not have seen with the normal light.

I currently tend to do this in people who have those cancer cells in the urine that we can’t find a reason for. And I also do it in people who I’m looking back in after they’ve already had a bladder tumor removed, either by an outside urologist, or myself, and we’re making sure that there is nothing else there.

This is less common now, but some people still do it. It’s called narrow-band imaging. And this basically helps see a bladder tumor based on its vascularity, meaning how many blood vessels there are. This is not quite as useful, in my opinion, as the blue light cystoscopy, but it can certainly help. And you can see again under the normal camera, and then under the special camera. It can help see things that we might miss with our naked eye. So, those are the diagnosis and evaluation.

And now I think the part that is most important and that I’ll spend the most time on is the staging and the risk groups for non muscle invasive bladder cancer. So, these are the types of bladder cancer, as you may already know. And what you can see here is there is something called carcinoma in situ, which is a high grade type of cancer that is growing only on the lining. And this is the lining of the bladder right here. And then there is another type of cancer called TA. And that is when it is on the lining, but it’s more on a stock, and it’s not growing in over such a large surface area. And then there is something called T1. And that is something where you may have roots growing into the layer of the bladder, but not yet into the muscle. And this is the stuff when you start to see things into the muscle. I won’t talk about those T2 and T3 today, I’ll just be talking about carcinoma in situ, TA, and T1.

Of people who are diagnosed with non muscle invasive bladder cancer, about 70% will have TA type of cancer, and 20% will have T1, and 10% will have carcinoma in situ. Again, the important thing I think to know is that T1 has those roots that are starting to grow towards the muscle. And so, there is a bit of a higher risk of that becoming muscle invasive. And when it invades the muscle, there’s a higher risk of it spreading outside the bladder. And so, that’s why we always try to stage these very carefully.

Dr. Amy Luckenbaugh:

What is the difference between stage and grade in non muscle invasive bladder cancer? When you see your pathology reports online and things like that, what you’ll see is a stage and it’ll be listed. And then you’ll also see a grade, and it will either say low grade or high grade. Grade is what the pathologist sees when they look under the microscope. And it’s basically how abnormal the cells are. Low grade cells tend to be closer to normal. They are more likely to come back, but they are not very likely to progress or grow deep into the bladder wall. So, recurrence is tumors coming back. Progression is tumors growing deep into the wall when it was not initially deep into the wall. And low grade is less likely to do that, whereas high grade tumors can both come back and can grow deeper into the wall.

And so, this is kind of a table showing what I was just talking about. You can see in that blue circle, the chance of progression, so growing deep into the wall, for low grade tumors is only around five to 10%. So, it’s pretty uncommon. Whereas for high grade tumors, even if it is a stage TA, only in the lining, there’s about a 15 to 40% chance it could grow deeper. And so, high grade, we tend to treat a little more aggressively.

This is something that I think is really important, and it’s a lot of information, but it plays a role in how you personally end up being treated. The AUA came up with these risk groups for bladder cancer based on stage and grade. And what it takes into account is how likely you are either to recur or progress. And it helps guide treatment strategies based on that.

So, for people who have a low risk type of non muscle invasive bladder cancer, and it is a small tumor, and it is a low grade tumor, they are the lowest risk type. And so, those type of patients we oftentimes survey. And then there’s a second category that’s kind of this intermediate risk type of non muscle invasive bladder cancer. And that can either be a bigger low grade type of tumor, or any high grade tumor that is under three centimeters and not T1, falls into this category. The high risk category is anyone who has T1, so the cancer that is into the lining, but not yet into the muscle. Any very big high grade TA, any carcinoma in situ, and anyone who has had BCG before without it working successfully, as well as any different type of cells that pathologists saw. And all of these categories really play a role in what treatment we recommend and what treatment you’ll receive.

So, for TA low grade tumor, they can come back about 50% of the time, but they progress only 5% of the time. So I tell people, you’re kind of stuck with a urologist for the majority of your life with this, just to keep a close eye on things. For low risk low grade tumors, the treatment options are either to observe, or to give a type of chemotherapy inside the bladder, often at the end of the surgery that you’ve had. And that can be either gemcitabine or mitomycin. And I’ll go into more detail about what those are towards the end of that. I tend to favor gemcitabine because it is tolerated just a little bit better.

If there is a low grade tumor, but it is a little bigger, then we will either observe, or we might consider doing a weekly type of chemotherapy in your bladder weekly for six weeks. And so, those are kind of the general options for low grade type of bladder cancer. And I’ll again talk more in more detail about each of the medications a little bit later.

Dr. Amy Luckenbaugh:

For high grade non muscle invasive bladder cancer that is still just on that lining, we… in some cases if it is a large tumor, would consider repeating the TURBT, looking again to make sure that everything is out, to make sure it’s not going deeper, and that we got it all. But for high grade cancer, instead of doing a type of chemotherapy in the bladder, that is when we start doing BCG medicine in the bladder. And typically, we do that weekly for six weeks. And if it was something where it is kind of a intermediate risk on those categories I showed you, we may recommend that you get that treatment at three months, six months, and then another six months after that to reduce the risk of it coming back.

And that kind of brings me to the T1. These folks are the people who have the tumor kind of growing into the lining right before the muscles. So, it’s the closest to the muscle. The risk of recurrence is quite high in these patients. But the real concern is the risk of progression. So, one out of three people will progress to muscle invasive disease. And so, it’s really important that we adequately make sure there’s no muscle involvement before we start treating you.

So, anytime there is this T1 type of cancer, we will do what’s called a repeat TURBT, where we look back in and we biopsy deeper to really double check that there’s no cancer in the muscle. Because about 20 to 40% of the time there can be cancer hiding there that was missed on the first resection no matter how good the first resection was. For these people, because of the risk of progression, not only do we give the six weeks of BCG, but we recommend up to three years total. And that’s obviously been changed a little bit because of BCG shortages, but this is in the ideal world.

And then there is the category of people who have a large volume of this T1 cancer that we might consider early bladder removal. And that’s an aggressive option, but it is an option. And specifically for people with a high volume of the T1 tumor, or a special type of histology, meaning the cells that the pathologist reviewed was a little different.

Carcinoma in situ, that is the high grade stuff that kind of grows on the lining in a bigger sheet. This is usually shows up, and is seen in the cytology, which are those cells we send from the urine sample without having to biopsy anything. And for this type of cancer, we treat it like it’s high risk. And you would get induction BCG, so the six treatments, and then three years worth. 10 years after diagnosis with carcinoma in situ, there’s about 20% of people who could still die from bladder cancer. And so, that’s why we’re so aggressive about treating this with three years of BCG, if we can.

And these are the special cases I kind of referred to earlier. There’s a select few of you who might have what we call a variant histology. That’s an uncommon type of bladder cancer that the pathologists look at and they see under the microscope. And some of those uncommon types tend to be more aggressive. And so, even if it is non-invasive, we sometimes consider early removal of your bladder because they tend to be more aggressive.

These are the National Comprehensive Cancer Center guidelines, kind of outlining what I had just said in those last slides. For low grade, you could either, and it’s a low grade low risk, you could do observation, or you could give chemotherapy in the bladder right after the surgery. And that’s gemcitabine or mitomycin. If it is still a TA, but it’s high grade, you could do BCG, or an alternative option is chemotherapy, or you could observe. And then, for T1 high grade, we would usually look again and repeat the procedure, where we biopsy your bladder, and then go on to do BCG, or in some cases rarely recommend removing your bladder depending on the factors I discussed earlier.

And what about how often do we need to be looking in your bladder? So, if you had low grade non muscle invasive bladder cancer, we usually would do look in your bladder three months after we remove that first tumor. And then we would look again somewhere between six to nine months later, and then we would look every year for five years. You wouldn’t need additional CT scans in low grade cancer. And then for the intermediate risk people, we would look in three months. And then we would look three months later. And then after that about every six months we do a cystoscopy, just in our clinic, not in the operating room, nothing like that. And then once a year for five years. For the high risk people, we typically look every three months for two years. And then every six months for five years. And then once a year. So, like I said, you’re kind of with a urologist for a long time.

Those are all the staging and risk groups that we just addressed. And I will now talk about the chemotherapy. This is chemotherapy that is given inside the bladder. So, it is given through a catheter. It’s instilled into your bladder, and then we would ask you to try to hold it for around two hours or so. This chemotherapy is given for low grade bladder cancer. And you can see a list of examples. I would say the most common one used today are either gemcitabine or mitomycin, and they directly kill the cells that could be floating in the urine. It reduces the risk of the cancer coming back, but it doesn’t reduce the risk of it progressing. It just specifically reduces the risk of cancer coming back.

Here are the ways that this can be given. And one of the common ways is that after you have a bladder tumor removed, while you’re still asleep, we put in the catheter, we put the medicine in, and then you wake up and we take the catheter out, and you go to the restroom. And that can reduce the risk of it coming back if there are multiple tumors by up to 56%. In some cases, if you’ve had a low grade cancer come back again, or it is a bigger low grade cancer, then we might recommend that you do it weekly for six weeks, and that reduces the risk of it coming back somewhere between 14 and 38%.

The major side effects of these are feeling like you have to pee more frequently, more urgently. In some cases it can shrink your bladder size, and permanently in some cases. And it can sometimes cause skin irritation if it gets on your skin during the administration.

The two major ones like I spoke about are mitomycin and gemcitabine. Gemcitabine is a newer one, and it seems to be tolerated a little bit better than mitomycin. And so, I tend to favor that if it is available. This is just the article for your reference that kind of tested gemcitabine. And what they did is they tested that medication versus just saline salt water medication. And what they found was a lower risk of recurrence in the group of people who got the gemcitabine, and very few complications, and that it was pretty well tolerated.

That covers the intravesical chemotherapy, so the treatment option for low grade type of non muscle invasive bladder cancer. Now we’ll talk about BCG therapy. So, BCG is given for high grade tumors, and still remains kind of the gold standard for what we have for this type of cancer. BCG is actually a type of tuberculosis that is given in the bladder through a catheter, and it activates your immune system to basically fight and attack the abnormal bladder lining. And it works well for high grade tumors and carcinoma in situ.

Dr. Amy Luckenbaugh:

Usually, we wait to give BCG for about four to six weeks after your bladder biopsy, or TURBT, because the bladder wall needs to be healed. And then we would give it once a week for six weeks. And after that six weeks, about a month later, we like to look in the bladder and make sure that everything has stayed, or responded appropriately. If it has not and it is still a not invasive type of cancer, we can try doing an additional six week treatment with BCG. And about 20 to 25% of the time in patients who BCG did not work the first time, BCG actually works 20 to 25% of the time in the second attempt.

And so, it often is worth trying again. And if BCG works, then we would do this therapy three months after your initial treatment, six months after your initial treatment, and then every six months.

This is referring to that maintenance BCG assuming it has worked. We often try to give this for up to one to three years, about every six months. And it would be three treatments those times. This reduces the risk of recurrence, and it also reduces the risk of progression. So both recurrence and progression are affected by this.

BCG is especially effective for carcinoma in situ. And up to 30% of people with carcinoma in situ can have no cancer come back at 10 years after the BCG treatment. And people who don’t respond, it is not so good. And so, we need to identify that pretty quickly. And we would do that by looking in your bladder and sending off cells from your urine.

The side effects of BCG. There are a number of them that can occur. Within 48 hours of BCG, the kind of common side effects that you may have, feeling like you have to pee more frequently, urgently, some burning with urination, sometimes blood in the urine. And some people have this feeling like they’ve had a flu shot, and just kind of feel fatigued. If those are the symptoms, we tend to say that is okay we can continue the BCG medicine, take tylenol, take ibuprofen. And we often can prescribe medications for bladder spasms and burning. If these symptoms don’t improve, we can reduce the dosage of BCG. We don’t like to go below about a third of the normal dose though.

More severe side effects can happen. And if they are kind of persisting over 48 hours after the BCG, then we would consider checking your urine to make sure you don’t have an infection. If you had a high fever, then we would probably recommend you coming into the hospital. And if it is a high fever, you may not be able to receive future BCG, but that’s something we would kind of assess on a case to case basis.

This is just a general algorithm of what I have talked about already. So, there’s kind of different categories of people. There’s people who are low risk to progress, meaning low risk for things to grow deep into the bladder, and those people may have a risk of things coming back. If they only have low grade cancer once, we may just watch, or give medicine in the bladder. If they have something come back multiple times and it’s still low grade, then we would do the chemotherapy in the bladder. And if they have a high risk type of cancer, or it’s likely to come back and progress, then we’d give the BCG medicine.

Dr. Amy Luckenbaugh:

So, we’ve talked briefly about BCG. And next we’re going to go to, what if BCG doesn’t work? So there are a lot of exciting options for this that are emerging. Truthfully, non muscle invasive bladder cancer high grade disease can be really frustrating as it tends to come back and it tends to also progress. And so, for people who BCG didn’t work even the second course of BCG, we can talk about a bunch of options. One option is to undergo a cystectomy, or bladder removal. And that is kind of the tried and true option, we know it’s effective, but there are a number of options that allow you to spare your bladder that are kind of emerging, and these include gemcitabine and docetaxel, BCG plus interferon, pembrolizumab, which is a newer immunotherapy that’s given systemically, so in an IV. And then there are a bunch of exciting trials that I’ll just briefly touch on a few of them before we end.

So, why is cystectomy kind of recommended in some of these patients? We know that if you have a high amount of T1, so cancer into the lining right before the muscle, that about 50% of people might actually have muscle invasive disease when we take out the bladder. And so, for people who have recurrent high grade T1, and there’s a lot of it, or there’s that special type of cell that the pathologist sees that’s abnormal, we may recommend removing the bladder, because we certainly don’t want to miss a muscle invasive type of bladder cancer.

But there are a number of groups that have looked at giving other medications such as gemcitabine docetaxel. It’s a combination of two medicines that’s again given in the bladder. And what they found was for people who BCG didn’t work, about 60% of patients who were treated with this had no cancer coming back at one year, and 46% had no cancer coming back at two years. Ultimately, about 15% of the people went on to have their bladder removed, but it did allow them a few years before requiring that. And so, this is something that could be done if BCG hasn’t worked prior to going into removing the bladder.

Another mouthful is nadofaragene firadenovec. And that is called in short, instiladrin. And what this is, is it’s actually a type of virus that is instilled into the bladder the same way BCG is given. And it was given for people again who BCG did not work. And what they found was quite again a good effect, with about 53% of patients with the carcinoma in situ having a good response, and no cancer at follow up. And then around 72% with the high grade TA or T1 having a good response. Overall, one year out from getting this medication, 30% of people had no cancer that had come back. So, this is another option that is a little harder to find and not quite yet out there as widely available as the gemcitabine and docetaxel.

And lastly, there is pembrolizumab. This is a medication that instead of giving in the bladder, it’s actually given through an IV, like it’s an immunotherapy. And this was tested in people and evaluated in people with carcinoma in situ and high grade bladder cancer that hadn’t responded to BCG. Overall, it was relatively well tolerated, with a complete response rate of 41%. Again, in people who BCG had not worked. But the difference with this, and it’s important patients know, is that it’s a systemic medication. And so, you have more systemic side effects, like diarrhea, fatigue, rash, and things like that.

So we just covered the refractory disease. And lastly, I will talk about some ongoing emerging therapies. So one that is ongoing is BCG medicine combined with a special thing that can make BCG work a little better. And it’s given similar to BCG in the bladder, and it’s administered once a week for six weeks. And then you can continue on maintenance therapy if it has worked. And it is pretty promising, and we’re pretty excited about that. So, there are some sites that are still enrolling patients in this, and so that’s an option for a disease that it hasn’t responded to BCG.

Dr. Amy Luckenbaugh:

One other trial that is currently enrolling is, again for people who the BCG did not work. And there’s three options for this trial, three different things you could receive. One is you could receive a medicine similar to pembrolizumab and an IV to reduce the risk of it coming back and immunotherapy. The other is a medication that is actually given in the bladder, and it’s this little pretzel. The pretzel is put in your bladder with a normal cystoscopy like you would have in clinic, and that pretzel contains gemcitabine. And slowly lets the gemcitabine chemotherapy out over time, rather than having it just given to you once a week for six weeks. And so, that is the other option for treatment in this trial. And then the last option is you could receive that or combine that with an immunotherapy. And again, this is currently enrolling in various places.

And this is by no means a comprehensive list, just two that I am aware of. So, ask around to your urologist, there are things that are out there for patients who BCG has not worked. And in conclusion, I just think that it’s really important that those risk categories of low risk, intermediate risk, and high risk be considered, because that is what goes on, and how we determine how best to treat you. I do think there’s still the role for timely cystectomy removing the bladder if BCG is continuing to not work. Although it’s a big surgery, really does have the best outcomes. And I think the exciting thing is that there are a bunch of options, and that everything is rapidly changing and expanding. So, although BCG may not work in some cases, there are a lot of options that do. Thank you very much, and I’d be happy to take any questions.

Stephanie Chisolm:

Thank you so much, Dr. Luckenbaugh. That was really comprehensive. And I think you covered a lot of some of the questions that came in. So, this is wonderful. And we have a little bit of time, so we will definitely get to the questions. I’m going to just go back to one of the first ones that we received, how fast typically does bladder cancer develop? And likewise, the transition from non muscle invasive bladder cancer to muscle invasive, in the case of those patients with high grade, what is the usual expectation as far as how quickly it can convert and become more aggressive?

Dr. Amy Luckenbaugh:

That’s a tough question. That’s a great question. So, we never know how long you have had it. It could have been in there for a long time and slowly growing. And people who have high grade disease and T1 disease, the evolution can be pretty quick. And so, those people we tend to be fairly aggressive. I know that when I give BCG to those patients, high grade T1 disease, I oftentimes instead of looking after the BCG is done in my office, I have them go straight to the operating room and look with them under anesthesia, and repeat biopsies right then and there to make sure that there is nothing there, to kind of save that time.

There’s no like crystal ball with how fast it can progress, but it certainly can be fast in some people. And some people can go years and years and nothing progresses, and then at year four of surveillance, all of a sudden, poof, they have a new tumor. And that’s I think the frustrating thing for us and for patients.

Stephanie Chisolm:

Thank you so much. Yeah, that is very frustrating. So, when you’re doing regular routine cystoscopy, it’s a pretty invasive procedure. How often do you recommend that people have urine cytology done to check for free floating cancer cells, or things like that? And is it really something you do in conjunction with your cystoscopy, or you can do that at a different time?

Dr. Amy Luckenbaugh:

That’s a great question. So, for low grade cancer, we do not do cytologies at all, because the cytologies are usually negative. It only really works for high grade cancer. And cytology is very good if it is positive. If it is positive we can say there’s probably something somewhere, and we definitely should be looking. If it’s negative though, unfortunately, it’s not very reliable. And so, we usually do, for people with any type of high grade non muscle invasive bladder cancer, we do the cystoscopy and the cytology together, so in conjunction. There’s not a great thing in the urine yet that can say, “Do we really need to have this cystoscopy?” That’s an area of research that is very like ongoing and warranted, because it is an invasive procedure. But right now there’s nothing that says, “Hey, your urine looks okay, we won’t do the cystoscopy this time,” we have to do both.

Stephanie Chisolm:

Okay. Great. This is very important information. Can you talk a little bit about those patients that have mixed grade type of non muscle invasive bladder cancer, predominantly low grade, but maybe there’s a few high grade? What is the concern there from your perspective as the urologist?

Dr. Amy Luckenbaugh:

That’s a frustrating question. I think that our tough question as urologists is, do we treat those people as if they are low grade, or do we treat them as if they are high grade? And I think if it is a single time that they have a low grade and it says, “Focal high grade,” then I usually treat those people if it’s a small tumor like they are low grade, but if it comes back, then I immediately switch to treating them as if it is high grade. And in those people I do check a cytology when I look in their bladder, even though it was predominantly low grade just to make sure that there isn’t something else going on.

Stephanie Chisolm:

So, when you go in and you do a TURBT, if there are multiple tumors, you would take all of the tumors that you could see out? So, when they do the pathology report and that patient is seeing that pathology report, how do they summarize that? How do we understand if you’ve got all these different sizes and shapes of tumors and sometimes even different grades, how should a patient look at that pathology report? And how does that drive the recommendations of their individual urologist?

Dr. Amy Luckenbaugh:

A good question. As urologists, we all do it differently, but if there are multiple tumors in different places, I like to make sure to separate them all out for the pathologist. Because what we send the pathologist is kind of just a pile of junk, and it’s not very easy for them to look at. So, separating it out helps them do a really good job of looking at each individual spot. And then as the patient, I would take into account, but what is the worst one, or the highest grade one? And that is what we as urologists will be looking at in deciding our treatment based on.

The multifocal, meaning multiple tumors, does kind of bump you into that either intermediate risk or high risk category, and not the low risk category, because they’re multiple.

Stephanie Chisolm:

That’s a great answer. know from a patient perspective, any TURB is too many TURBs. But is there such a thing as how many TURBs a patient can endure? What is the general rule of thumb before you begin to think, “Well, maybe we need to go on to something bigger and more heavy duty to attack this cancer, to treat this cancer”?

Dr. Amy Luckenbaugh:

That is tough. I think in low grade cancer, many patients can endure TURBTs indefinitely, in low grade cancer. And sometimes even low grade cancers now we look in the office and just burn them, because it’s been low grade for five years and we know it’s low grade, instead of taking people to the operating room.

In high grade cancer it isn’t necessarily that we worry that their bladder can’t handle it, it’s just that we worry what will happen if they keep coming back. The more they come back, the more deep they’re likely to go, and the more likely they are to spread. So, it isn’t per se your bladder is resilient and can handle it, it’s more we just want to get to it before those cells start to creep outside.

Stephanie Chisolm:

That’s a great answer. I appreciate that very much. So, I know that sometimes patients are sent home with BCG and asked to hold it for the two hours before they naturally void it out on their own. And then they have instructions for how to keep it safe and clean. But what about intravesical chemotherapy? Is the patient ever sent home with chemotherapy still in their bladder and expected to take care of that? Is that something that commonly happens, or is it different with chemo?

Dr. Amy Luckenbaugh:

It actually it does commonly happen. If it’s the chemotherapy that we give right after the procedure, the single dose oftentimes the patient’s still waking up from anesthesia and everything. So they don’t have to worry about that, because we drain it out in the recovery area before they’re ready to go home. But with something like gemcitabine where you’re getting it weekly for six weeks, we can also send you home with that chemotherapy in the bladder with similar guidelines on what needs to be done and how to do it.

Stephanie Chisolm:

So, in general, and I know we’re in the middle of a BCG shortage right now, but when patients are able to get BCG, are there long-term side effects that we see with the BCG installation inside the bladder?

Dr. Amy Luckenbaugh:

Yeah. The BCG side effects are often cumulative. So they can get worse with more BCG, unfortunately. Some people rarely have side effects at all, and that’s great. And other people gradually start to develop side effects, like frequency of urination, urgency of urination, burning. And some people very rarely can develop almost what we call an N stage bladder from BCG, that it’s so small and so contracted, that they are urinating constantly. It’s not common, but it’s something that can happen. And so, it’s common as you’re getting the BCG for things to kind of… They starts off okay, and then you slowly have side effects that are altered. And we can give medications to help with that, and we can also reduce the dose, and that sometimes can help with that as well.

Stephanie Chisolm:

Thank you very much. So, given that the BCG shortage isn’t getting any better anytime soon, I know you have a bigger practice at Vanderbilt, so I’m sure you’re getting an adequate supply of BCG to treat your patients, but I know not everybody is being seen in the large academic institution where they might have an adequate supply. So, when they’re being treated in their community, do you have a sense of what the community urologist is able to provide to them in lieu of BCG if they can’t get it? What are some of the things that are being used in the community?

Dr. Amy Luckenbaugh:

Gemcitabine is being used instead of BCG in the community. And some practices are reducing the dose, and cutting the dosage in a third and splitting the rest of the thirds amongst other patients to get some BCG rather than non. That is kind of my limited knowledge of what goes on. Yeah.

Stephanie Chisolm:

Here’s a particular question. How does the FISH test fit into monitoring?

Dr. Amy Luckenbaugh:

That’s a good question. I don’t often use the FISH test. Some of it is a financial reimbursement thing. But I think that if we have doubts or questions about abnormalities and cells, specifically the cytology, getting the FISH can give additional information about whether there is an area of concern we should be focusing on. Because sometimes the cytology can not be perfect, and FISH can help provide backup for the cytology. But I wouldn’t use it as routine monitoring, or routine testing, or anything like that.

Stephanie Chisolm:

There’s been a lot of talk about some of the discomfort that goes along with both a cystoscopy and even for the BCG. Does topical lidocaine help in your mind, when you see that? Do you use that with patients if they have challenges with the cystoscopy or with the BCG installation? And does that impact both?

Dr. Amy Luckenbaugh:

We do use it. I do not think it impacts things negatively at all. And if people have difficulty, we use it prior to assist you, also we use it prior to our cystoscopies, and it does not impact the effectiveness. That’s like somewhat of a controversial topic, but I do not think it does.

Stephanie Chisolm:

Okay. Great. So, does the risk of recurrence and progression lessen in high grade T1 cancers with the passage of time once it’s successfully treated with the TURBT and the BCG?

Dr. Amy Luckenbaugh:

Yes. Yes. It still exists, but of the biggest predictors is, after BCG, the first time you’ve gotten it, if we look in your bladder and there is cancer back, that is one of the biggest predictors of future progression and future cancer coming back. So, as we get further out we feel better that it is less likely to happen, and that’s why we decrease that frequency of cystoscopy and everything like that.

Stephanie Chisolm:

Great. there’s a question that came in about the AUA, the American Urological Association, treatment and monitoring protocols for high grade bladder cancer seem to be based on experience with BCG. If you’re having chemotherapy and still the gem and docetaxel, should the monitoring protocols be about the same as they would be for the BCG, or more aggressive, more frequent scoping, or less aggressive? What’s the general take on that? What is your thought?

Dr. Amy Luckenbaugh:

Some of it is nuanced and provider-specific, but I think if BCG hasn’t worked, I tend to survey people a little more closely than the guidelines suggest, because BCG hasn’t worked and I want to make sure whatever subsequently is being used does work.

Stephanie Chisolm:

So, if somebody were to have experienced something like cystitis that came about from their BCG, what are their options for treatment?

Dr. Amy Luckenbaugh:

So, in terms of their cancer, they could still get BCG at reduced dose. In terms of their side effects, there are things that we can use. There’s things over-the-counter such as Azo or Pyridium that can be used to help reduce the burning that can be given concurrently with BCG. There are things for bladder spasms that can be given. Like oxybutynin is an example, or Mirabegron is another form, that can be given to reduce bladder spasms.

Some people have significant spasms when the BCG is instilled. And so, there are people that we have them on long-term bladder spasm medication, but we also ask them to take an extra as needed dose before they come to get the BCG so that that BCG can be helped better. Sometimes in people who have spasms so severe, sometimes we leave a catheter in, and send them home with it. And then they take it out once they’ve drained the BCG so that they’re able to hold the medication in. So those are kind of some options both to help continue to get BCG, but also for management of the symptoms from the BCG.

Stephanie Chisolm:

Sort of an interesting question, what size is considered a large tumor? And we’re still going to stay in the non-muscle invasive. What would you consider a large tumor? And do you have any sense of the largest tumor that people have seen? And most of them, if you were thinking about the average tumor size, is usually what?

Dr. Amy Luckenbaugh:

Let’s say the average tumor size is somewhere between two and five centimeters, about. The guidelines use three centimeters as the cut-off to move someone from the intermediate risk category to the high risk category, and some of that is based on research that has been done. But I would say two to five centimeters on average is its average. And there are times where bladders are completely full of tumor. And those patients, I think one thing to keep in mind if you are one of those patients is that that sometimes requires multiple trips to the operating room to get your bladder to be not completely full of tumor. And that’s in part because we can only safely scrape for so long because of things that happen with fluid and everything like that.

Stephanie Chisolm:

So, are there any contraindications for the practice of physical exercise after a TURBT, or during intravesical therapies that you can recommend, or that you’ve seen patients have challenges with?

Dr. Amy Luckenbaugh:

I usually tell people right after a TURBT, depending on the size, to take it easy in terms of no heavy lifting for greater than 10 pounds for about 48 hours. There’s no data behind that, but I think your bladder is forming a scab, and so that straining or pressure can kind of burst the scab off and increase the risk of bleeding. But otherwise, I would say there’s pretty limited physical activity restrictions. And during intravesical therapy, you can continue physical activity. You shouldn’t have intercourse within about 48 to 72 hours of receiving it. But besides that, you can continue normal physical activity during the intravesical therapy.

Stephanie Chisolm:

Great, okay, good. Does an evidence of a prostatic urethral carcinoma in situ in addition to what might be in the bladder affect the prognosis?

Dr. Amy Luckenbaugh:

It affects the prognosis a little bit, because carcinoma in situ in the prostatic urethra is a little harder to get rid of. It doesn’t respond quite as well to the BCG, because the BCG sits in your bladder, but it can’t sit in the urethra tube. And so, it doesn’t have as much contact with the urethra tube as it does with the bladder. It’s not to say that we don’t try often to use it, but it just doesn’t work quite as well as it does in the bladder.

Stephanie Chisolm:

There’s a medication-specific question, and I’m not sure if you have the answer. But if you’re taking tamsulosin, does that impact or affect BCG?

Dr. Amy Luckenbaugh:

No. No, it does not. Not at all. Actually, a lot of people we wind up, men specifically, putting them on it throughout the course of the treatment.

Stephanie Chisolm:

Okay. That’s excellent. Thank you. Can BCG failure be due to steroid drugs being taken while having the infusions, if you’re on steroids?

Dr. Amy Luckenbaugh:

It is a little bit dependent on how high of a dose of the steroids. If it’s a low dose, like daily prednisone kind of thing, typically not. But if you’re on big doses of prednisone, or big doses of steroids, or big drugs that affect your immune system for arthritis or things like that, we may work with your rheumatologist or primary doctor to help adjust those, just to make sure to get the maximal effect of the BCG. It usually takes a pretty high dose though for it to not be effective.

Stephanie Chisolm:

I have two location questions. When the CIS is in the dome of the bladder, which is assumed to be the thinner part of the bladder, does that mean it’s a higher risk of progression into the muscle?

Dr. Amy Luckenbaugh:

No. So, the dome of the bladder is slightly thinner, but what really is important about the dome is it’s the hardest to biopsy or scrape tumors off of because it can rupture like a water balloon. And so, the real concern with stuff at the dome is on us, making sure that we get as deep as we can safely. It doesn’t increase the risk of progression to muscle invasive, though.

Stephanie Chisolm:

If you have more than one tumor, but they’re all clustered in the same location, same area of the bladder, is that a good sign, or maybe more of a risk? What’s the risk there?

Dr. Amy Luckenbaugh:

It’s hard to say. We treat multiple tumors as multiple tumors, and we associate it all the same. But the question is a good one, because are there multiple tumors and they’re just little satellites popped off of the main tumor, and that’s why it’s all clustered in one location? Possibly. But we don’t have quite enough information about that to know.

Stephanie Chisolm:

This is kind of a timely question. When on immunotherapy like BCG, is there any concern about vaccinations for flu, or for COVID?

Dr. Amy Luckenbaugh:

No. I do not think so. I tell everyone they should go ahead and get their normal vaccinations, and do all of that regardless of the BCG, or intravesical chemotherapy being administered.

Stephanie Chisolm:

Okay. And then the last question has to do with BCG. I know that it in some cases needs to be mixed under a hood, because it’s the attenuated virus and everything. But the question is, does it have to be administered in a negative pressure room with an N95 on?

Dr. Amy Luckenbaugh:

The people who administer it generally do wear an N95 for their safety. They do not do it in a negative pressure room, it’s administered in our normal clinic rooms in general. But they do wear gown, gloves, and an N95, and face shield to protect themselves.

Questions submitted that were answered in writing:

How do you know if a CIS is or is not already Muscle Invasive Cancer?

They determine this by doing biopsies and TURBTs that take samples of muscle as well as the tumors. This shows whether the cancer is in the muscle.

Why is CIS considered high risk?

You can read more about CIS at: https://bcan.org/facing-bladder-cancer/bladder-cancer-types-stages-grades/. Generally it is considered high risk because pattern of the cells.

Why wouldn’t blue light cystoscopy be used on all patients if it picks up the cancer better than the white light cystoscopy?

Blue light is a “newer” technology and the equipment for it is quite expensive, so not every clinic/hospital is able to purchase this equipment.

If cytology is negative for High Grade cancer, how can one be sure that the bladder does not have Low Grade cancer?

They use TURBT to determine this. Generally speaking, biopsies and TURBTs are moreaccurate than cytology. Cytology is not accurate or often used for low grade cancers.

When on immunotherapy like BCG is there any concern about vaccinations for flu or Covid?

Patients are encouraged to receive vaccinations like the Covid or flu vaccine, while they are undergoing intravesical treatment. Always consult your healthcare provider if you have concerns about side effects from vaccines. You can also listen to a more in-depth here: https://bcan.org/what-you-need-to-know-about-covid-vaccines-and-bladder-cancer-with-dr-seth-lerner-and-dr-laila-woc-colburn/