Understanding Bladder Cancer | Muscle Invasive Bladder Cancer (MIBC)

November 29, 2021

With Dr. Tracey Krupski

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

Year: 2021

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Part 1: Understanding Muscle Invasive Bladder Cancer and Indications for Cystectomy

Video (18 min) | Transcript (PDF)

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Part 2: Preparing for Surgery

Video (25 min) | Transcript (PDF)

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Part 3: Quality of Life and Q&A

Video (17 min) | Transcript (PDF)

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Full Transcript

Morgan Stout:

A bladder cancer diagnosis can be terrifying to a patient and their family. What do you need to know about muscle invasive bladder cancer, MIBC and the treatment options for it? BCAN is delighted to have Dr. Tracey Krupski, a professor of urology at the University of Virginia today for today’s program. Dr. Krupski is a surgeon who’s specialty is urologic oncology and her research focuses on health related quality of life and outcomes of robotic versus open surgery for muscle invasive bladder cancer. Welcome Dr. Krupski, I’ll turn it over to you.

Dr. Tracey Krupski:

Thank you, Morgan. That was very nice introduction. And I too would like to thank the sponsors that you can because it really is through their support that we are able to provide educational programs like this so thank you very much. So today we’re going to talk about muscle invasive bladder cancer. I am Tracey Krupski. I originally am from New York and then I went to Virginia, but I did my urologic oncology training at UCLA before I came back here.

And now that I’m at UVA, I predominantly see bladder cancer patients both the non-muscle invasive kind, which is usually how they present and then of course, muscle invasive bladder cancer as we already alluded to. So I have had funding related to bladder cancer through the American Cancer Society and I’ve been part of some industry sponsored trials for new bladder cancer therapies which are since complete so I have no ongoing disclosures right now.

So what I thought we’d try to talk about today and we may feel like we’re jumping around, but I was going to try to take you through the way I think of presenting this to my bladder cancer patients, is first, what are the indications for a cystectomy? There can be several different reasons that somebody is going to undergo a cystectomy, and then along with that, we want to talk about who should potentially consider chemotherapy before having their big surgery.

Then since I’m the surgeon, we’re going to touch a little bit on nonsurgical options, but mostly we’re going to spend some time talking about preparing for surgery, the expectations during surgery, what happens after surgery immediately and then how this could influence your longer term quality of life. And then I just wanted to tie up with some exciting new things that could be coming along the pike for bladder cancer.

It’s been a really exciting time the last maybe five years or so. For 20 years, we hadn’t had anything for bladder cancer and now we’re just having explosion of information and new treatment options, so it actually is very satisfying. So let’s just dive right in. Usually my experience is the BCAN population is quite sophisticated and usually ask me a lot of really poignant questions, but let’s all start from same ground level and make sure that we’re on the same page, so to speak.

Dr. Tracey Krupski:

So hopefully you can see my mouth, but if not, I can just kind of walk you through it. The bladder is comprised of three layers, the mucosal layer, which is the surface. And I tell people that’s like the mucosa of your mouth, that inner lining that touches, in this case, the food, but here, the urine. Then there’s the scaffolding layer, that’s this kind of circle, or we call it the lamina propria. But it holds the bladder in an actual circle, then the muscle that does the contracting.

So the depth of invasion, not necessarily the size is really what’s most important. If it’s a surface tumor like this, it means it’s jutting up off of the mucosa with a little stem and it doesn’t go deep. If the root system like a plant is going deeper into the first layer, the laminal layer, it becomes this T1 tumor. If it was just at the surface, it’s a Ta tumor. And then if it’s going deep into the muscle below that surface that you can see, it’s a T2 or T3 and then T4 means it’s trying to grow outside the bladder into adjacent organs.

Endoscopically you can’t really appreciate whether something’s all the way through or not, but you can often on imaging or if the bladder is totally removed, that’s when you know if it’s gone outside the bladder. So this carcinoma in situ is a little bit different. It is non muscle invasive because it’s on the surface, but by definition, it tends to act a little bit more aggressively so we keep a very close eye on carcinoma in situ.

Dr. Tracey Krupski:

The focus of this talk is T2 or those deep tumors going into the muscle, or muscle invasive bladder cancer. So just for you to visualize, endoscopically, we diagnose these by looking through a camera into the bladder, and this is a very frangula little papillary tumor. It looks like a little broccoli flowerette or a sea anemone. This is almost certainly a Ta tumor, low grade, not going to be muscle invasive and tends to keep coming back, but doesn’t spread to other organs and become particularly dangerous.

This on the other hand is kind of a representative picture of a tumor that’s much more nodular. We kind of call this sessile, meaning it has a broad contact with the bladder base and it just looks a little bit more hefty and aggressive. So for somebody who walks in the door of a urologist’s office with bladder cancer, 70 to 80% are going to be this low grade, non muscle-invasive kind. They tend to come back but don’t tend to spread.

20% of the time you will come in the door with a bad cancer, a muscle invasive cancer. It’s not that these gradually become these. Most of the time, you actually walk in the door with a bad cancer. These unfortunately are dangerous, they can be lethal and so we want to treat them quite aggressively. This is one brief non muscle invasive slide. So for that first papillary type picture this is where you’ll hear things like what is the size of the tumor? What is the grade of the tumor? How often does it come back or are there more than one?

When you hear those kind of words or lingo, that’s non muscle invasive cancer and we’re worried about risk stratifying them in terms of how quickly or how often they’ll come back, not necessarily in terms of prognosis like being lethal or spreading to your legs, lungs or lymph nodes, et cetera. So if you hear something like low, intermediate, high risk, this is for a recurrence bladder therapies inside the bladder, all of that is related to non muscle-invasive disease, not muscle invasive disease.

So the obvious reason that we’ll see on the next slide is muscle-invasive bladder cancer, that’s of common reason to take out someone’s bladder, but we can do it in the setting of these non muscle-invasive tumors for certain characteristics. So if it’s T1, that means it’s going down into that first layer of the bladder, high grade. Grade always refers to how does it look under the microscope? Is it aggressive appearing or not aggressive appearing?

Dr. Tracey Krupski:

And so if you have a T1 tumor going into the first layer, high grade and it has some of those other features like it keeps coming back quickly, we can’t seem to remove it entirely when we do this resections endoscopically or it has any of these funny types of tumors that are a different cell type than the normal lining of the bladder. So the normal lining of the bladder is urothelial cancer. If you have a cancer that’s called micropapillary, nested, plasmacytoid, neuroendocrine, sarcomatoid, these are aberrant or different histologies that tend to act more aggressively.

So we often think of removing the bladder for these or high grade T1 tumors that keep coming back that that could be our window for cure. So there could be an indication other than just being less invasive. Not the focus of this talk but if you’ve done anything with bladder cancer, you know we often treat BCG, we use non muscle invasive bladder cancer and treat it with BCG. If you have an unresponsive tumor to BCG, you may also undergo a cystectomy.

The most common reason is as I showed in those first pictures, you have a bad cancer that’s going into that muscle layer or beyond, that’s maybe your first tumor ever and that is the main indication to consider removal of the bladder. People ask, can you just remove part of the bladder? Why do you have to take the whole thing? Well, urothelial cells line everything that’s in contact with urine so the upper part of the right kidney and the tube to the right kidney, the upper part of the left kidney, the tube to the left kidney and the entire bladder is covered with urothelial cells.

So most of the time it’s a field defect and it’s going to be another cancer cropping up in the lining of your bladder even if you remove one. So there’s a couple times if it’s a diverticula, which means there’s only cancer in the outpouching, a very large capacity bladder or a small tumor right at the very top, those would be the only times your doctor may discuss with you doing just a partial cystectomy.

Dr. Tracey Krupski:

If your tumor invades the prostate and you’re a man, you have to have the whole bladder removed because that’s by definition spread into another organ. And occasionally people have opted for chemo radiation, we’re going to talk about that in a second. But if that fails, then you could consider removing the bladder at that time. So those are all the oncologic reasons to remove a bladder. There are other reasons, multiple sclerosis, things like that, spinal cord injuries. We’re not talking about those, we’re just talking about cancer reasons.

There’s lots of different guidelines that you can look up to follow on the internet. There’s non-muscle invasive, muscle invasive, nonmetastatic, there’s European guidelines, there’s the AUA, which is our national organization. And I’m sure you’re familiar with the National Comprehensive Cancer Network. They also put out these algorithms and flow sheets to help figure out how we should best treat cancer.

So if you have muscle invasive bladder cancer, there is a choice of the two main pathways to be treated. There is surgical removal of the bladder or there is chemo radiation. So this first one is cystectomy, removing the bladder. If you’re a man, you remove the prostate along with it. If you’re a woman, often part of the uterus, cervix or some portion of the vagina may be removed as well. You have to reroute the kidneys, you have to use intestine for a reservoir. And we traditionally remove lymph nodes, which are near the large vessels to your legs that give you blood flow.

So it’s a major operation dealing with a lot of different organs. If you choose to not do that, you may be older, maybe medically you don’t think you’re going to do well with that big a surgery, you may opt for what we call chemo radiation or trimodal therapy. That means you do an endoscopic surgery to remove all the visible tumor and go as deep as we could to try to get rid of everything that we can see on the inside of the bladder then you get radiation and chemotherapy at the same time.

Dr. Tracey Krupski:

And that may go on for five weeks while we are treating the muscle invasive bladder cancer and treating your entire bladder with a combination of radiation and chemotherapy. That is kind of represented. I just wanted to show you these national comprehensive guidelines. So if you look, you have stage two. If you can remember back to that original diagram, that means it’s the deep going into the muscle, muscle invasive bladder cancer.

And if you’re a cystectomy candidate, you would proceed along this side of the pathway. If you don’t want to have a cystectomy or you’re not medically maybe strong enough for it, we’re going to this star part of things. So this little segue here is talking about not doing surgery for muscle invasive bladder cancer, but rather considering chemo radiation. So a few words about chemo radiation. Again, this is what I was alluding to.

It’s very important to go under anesthesia, have the urologist scope you, look in through your urethra and remove as much visible tumor as they can. That means going almost all the way through the muscle to the point where they get to the fat around your bladder and then you keep a catheter for a little while while you heal that little hole and then you can consider getting the radiation to both the bladder, as well as some of those lymph nodes that we removed during the surgical part.

So the pelvic lymph nodes and the bladder get radiated and we are able to then treat you with chemotherapy, which is sensitizing. What that means is it’s making the radiation work better. So we use that in conjunction, they’re synergistic, so to speak. Occasionally you’ll get some markers put in the bladder to sort help focus where the radiation needs to go. And there’s a 5 to 7% chance that after just a really, really aggressive resection in the operating room, you may be able to be rendered tumor free. That’s what T0 means, no more cancer in your bladder if you have a really aggressive resection.

Dr. Tracey Krupski:

Now that’s not standard, but that’s part of why we call it do all three, a good resection, chemotherapy and radiation. So if you’re thinking about this option, it’s going to save your bladder, right? You don’t have to worry about removing the bladder and what are you going to do for a reservoir, this is a third of the patients are done. They’ve kept their bladder, their cancer doesn’t come back and they don’t have to worry about it.

A third go on to have their cancer come back, but it’s still within their bladder. So they can go back to that cystectomy option again and then a third of the disease will progress to other organs and there would be no role for moving the bladder anymore. So in a sense, you can think of it as like two thirds respond initially and do well and maybe up to 30 to 40% continue to do well and never need anything else after chemo radiation.

So this is a reasonable option. You should not just get radiation alone. Radiation alone is not as curative as chemo radiation. And if you do chemo radiation and you’re closely followed and you go on to have recurrence in your bladder, the bladder cancer comes back, then we remove your bladder. That’s what salvage cystectomy means, meaning we didn’t do it up front, we’re going to do it after you had this other therapy, you still do as well. Now that it’s not quite as high of level evidence, but it can be done and you can be cured by removing the bladder if chemo radiation did not work. So here’s just one little graph, we call these survival curves. So these are overall survival curves. These are people who got radiation only, and these are the people who got chemotherapy and radiation. And when these curves are separated like this, there’s a much better chance of being cured with the chemotherapy combined with radiation.

Again, just to emphasize, close follow up. Somebody needs to look into your bladder every three months to see if that cancer’s coming back. CTs or pet scans are not good for this because urine tends to pick up the pet tracers so you can’t tell anything that’s going on in the bladder. We don’t want your kidneys to get blocked, that’s what hydronephrosis means. And the ideal patient is one who had a solitary muscle invasive tumor in one spot that’s been fully resected.

Dr. Tracey Krupski:

If it’s sort of dotting all over the bladder, encompassing the whole half wall of bladder, those are not going to respond as well as a small tumor, fully resected, one spot, not blocking any kidneys, that type of thing. So chemo radiation.

Dr. Tracey Krupski:

What about the bladder? So if we talk about doing a cystectomy, so you say, “I’m not going to do that chemo radiation thing. I don’t want to do that, I want to just surgically have my bladder out.”

Well, we’ve kind of had a shift in our philosophy. Originally, we thought only the people who had the really bad tumors, like it went all the way through the bladder wall would we recommend they take chemotherapy before the surgery. But more recently we’re recommending neoadjuvant chemo to anyone with muscle invasive bladder cancer if they can have it. So anyone who comes in with a muscle invasive bladder cancer, it’s pretty standard of care to recommend they discuss chemotherapy with an oncologist.

It doesn’t mean that you have to take it, there may be medical reasons why you can’t get the chemotherapy and you really need to get cisplatin chemotherapy. That’s a certain kind of drug. If you substitute carboplatin for it, it’s not very effective and you should just go ahead and do surgery without chemotherapy if you cannot get a cisplatin based chemotherapy. So ideally, that makes this a very long journey because this chemotherapy usually is given for three or four cycles, which means you get it every three weeks three times. So anywhere from 9 to 12 weeks, it’s going to take to finish chemotherapy.

You need to have a little time to get stronger so that you can head into this big surgery feeling like you have a good appetite, good strength, good performance, you can do things. Those are the most important criteria. So we would recommend that you discuss it anytime you have muscle invasive bladder cancer. Now who might not get it? So the cisplatin, this is the drug that I was talking about. It’s given intravenously. It can be combined either with one other drug called gemcitabine or with three other drugs and we call that MVAC.

Dr. Tracey Krupski:

They have neuropathy. So this is the kind of chemotherapy where people are trying to do the buttons on their shirt and their fingers don’t work as well, they get stiff. It can cause a flare in your gout. But one of the bigger things, the two biggest things we worry about is myelosuppression, meaning during those nine weeks of getting chemotherapy, you’re at risk to get an infection because your body is not making its fighter cells so you may be more likely to it get a pneumonia or a kidney infection or colitis or something like that.

And if your counts are too low, meaning when they check your blood counts for your leukocytes, your natural killer cells, all your immune cells, if they’re low, they may have to postpone giving you the chemotherapy. And the chemotherapy is not good for kidneys. So when you have impaired kidney function, maybe you’ve had bad diabetes for a long time, maybe you’ve had kidney stones, maybe you’ve had bad high blood pressure, heart disease. If your kidneys aren’t in fairly tip top shape, they’re not going to tolerate getting this drug that is very hard for the kidneys to metabolize. So you have to be fit again for chemotherapy also.

If your kidney function’s not good, if you keep trying to get the drug and your blood counts are so low that you’re not going to be able to resist any infections, then sometimes you can’t get the chemotherapy. But it’s always worth discussing these things and talking to the oncologist. And usually I personally would recommend starting it and seeing if you have any of those bad side effects.

The vast majority of muscle invasive bladder cancer patients actually get through this kind of chemo quite well. It’s much better tolerated than some for like chemos for breast or colon cancer or some of the more common ones. There’s some data we would generally tell people that you have increased your overall survival by about 5% if you take chemotherapy first, and your bladder cancer survival also goes up. So this is over three years, it’s also over 10 years. And in this other trial, same thing.

Dr. Tracey Krupski:

If you took the chemotherapy first, the chance of dying was 59% with no chemotherapy versus 65% with chemotherapy. And then for bladder cancer specific, 35 versus 50%. So generally it is improving overall survival to get the chemotherapy first. So we are going to talk a little bit specifically about surgery and preparing for the surgery. So if you were to walk in my office, we would sort of have gone through those things that we just touched on.

First decision you would have to make is, do we think you should do surgery or do we think you should go that chemo radiation route. If you do chemo radiation, urologist is still involved because we have to do that maximal endoscopic resection and then we’re going to keep looking in your bladder every three months. So you still see your urologist, but you will go see these other doctors. If you say, “Nope, I’m going to get it out. I want that bladder out. I want to do surgery,” then your second decision is, should we do chemotherapy or not?

I just gave you groundwork that I would strongly recommend chemotherapy before doing the surgery but again, you have a personal choice. You can say, “The data doesn’t support it for me, I don’t want to get chemotherapy first. I want to just do the surgery.” Or maybe we look at your kidney function and we say, “It’s really probably not a good idea, it’s just going to delay things and it’ll probably hurt your kidneys too much to proceed.” So there could be reasons to do chemotherapy or not do chemotherapy.

And then the third decision we have to talk out is you’re going to have your bladder removed, we’ve decided on chemotherapy, what are we going to do with your urine once your bladder’s gone? So what type of reservoir are we going to put your urine in? And it’s a big surgery. So the things you have to sort of talk about, I’ve alluded to, but when you remove the bladder, it’s going to do the bladder, prostate, seminal vesicles for a man, for a woman, you might remove part of the uterus, fallopian tubes, vaginal wall.

Dr. Tracey Krupski:

This is depending on what your muscle invasive bladder cancer is like, how stuck those organs are together. But the goal is that you have to remove anything that might have cancer in it, so that’s a consideration. And then for the reservoir, we need to be thinking about what kind of bowel we’re going to use and what kind of reservoir for you you’re going to have. So large bowel is going to use your colon, that’s going to change a little bit about your postop life long term.

Small bowel, you probably won’t notice it as much from a colon or a defecation standpoint, but it’ll have different electrolyte abnormalities and different things you’ll have to watch for. For you on your day to day basis, what matters for incontinent or continent means is the urine just continuously pouring out into some kind of bag or receptacle, or are you continent, meaning you have to access the bladder through some kind of tube, either naturally urinating or potentially putting a tube in you.

So those is what we mean by continent or incontinent. This is the one time I’m the one doctor that gets to tell my kids that geometry actually matters, that I use geometry in my day to day life. And what that has to do with is LaPlace’s Law. If you have a tube, a long narrow tube like a sausage, that does not store anything. Urine is just going to run straight through there and that’s going to be an incontinent type of reservoir because there’s no… The wall tension is so high it’s just going to squirt the urine straight out.

Dr. Tracey Krupski:

What has to happen if you’re going to store urine is you have to create a sphere. So our bladder was made into a sphere for a reason. It’s not so that the urine comes out better, it’s so the urine gets stored better. If you have a circular shape, you have a very low pressure wall so that lets the urine accommodate without constantly having a spasm and squirting out the urine. So anything that we make has to be made into a sphere if you’re going to try to have some kind of continent reservoir.

So here’s just a cartoony type picture of the easiest thing for us to make, the easiest thing for you to take care of but it’s this tube, right? The urine just comes down from the right kidney, from the left kidney, just gets peristalsis, pushed right out into the skin and drains into a bag on your skin. So this is called an ileal conduit or urostomy, very similar to colostomies that people get that just continuously drain stool into a bag.

This is small intestine so it has the least electrolyte abnormalities and it has the smallest amount of time that the urine is in contact with the bowel. And that’s important for these electrolyte abnormalities because urine is not supposed to be in contact with the bowel, that’s what the urothelial cells were for. So this is an incontinent reservoir called an ileal conduit. And in general, in the United States, this is the vast majority, 60 to 70% of people will have a conduit after this surgery.

Now in Indiana is a continent diversion. So these are continent pouches. I just picked Indiana, it’s the one I make. It’s fairly common but you can hear about a UCLA pouch and a Florida pouch and a Kock pouch and a Studer pouch. There’s lots of different names, but essentially these are continent diversions that use colon. And we capitalize on the natural valve between your small intestine and your large intestine, and that’s what keeps you dry.

Dr. Tracey Krupski:

So it’s a little bit hard to imagine and I don’t know that you guys can see my piece of paper. But if you imagine that you have a tube, that’s a colon. So this is your colon. We open the colon up away from its blood supply and then sew it into a bigger circle like that. So again, that’s for the storage part. So it becomes almost kind of like a clam shell. It’s somewhat spherical so it will store urine and then you would put a tube in the one way valve through your skin to empty your urine every four to six hours and that would be forever.

So you have a little medical alert bracelet often. It says I don’t have a bladder, my urine comes out through my belly button. And that’s what this is depicting, what I just tried to do with the piece of paper. You fold this intestine over, you reconnect the regular bowel with all of these. The stool part gets reconnected so you still eat and drink normally, but then you have this valve mechanism that you use to put in through the skin and drain your bladder. So it’s a little bit more work for the surgeon, it’s a little bit more work for you.

And I put on here chronic loose stools. So what the colon is meant to do is reabsorb water. So it reabsorbs water that you eat and drink on a daily basis. So you’re more prone to chronic loose stools if you have to use colon to make your continent pouch because now there’s no… the whole right colon is used for urine, it’s no longer used for stool.

Neobladder is probably much more common these days. People will try to build you a new bladder. We mostly use small intestines, so we use ileum also. But you again, have to open up that tube and sew it by hand into a circle. And that circle is what’s going to allow the urine to be stored and then you have to relearn how to urinate because there’s no muscle in this intestine. So you relearn how to urinate. Usually it’s by relaxing your pelvic floor. And then occasionally you’ll have to irrigate yourself with the mucus from the bowel or if you can’t void successful, you may have to empty it through your natural urethra, either your penis or the urethra for a female.

So again, now in this case, it will have a little different electrolyte abnormalities because the urine is going to be sitting in contact with the intestine and there’s going to be transfer of electrolytes, potassium, sodium, phosphorus, magnesium because of this new setup where urine is going to be sitting there dwelling between you either voiding or catheterizing, cetera.

Dr. Tracey Krupski:

Anytime you have to do more work, there’s a few more risks of things not totally healing correctly because there’s a lot more sewing and a little bit more for the patient to learn how to deal with afterwards. But it is a continent and in this case it’s attached to your natural orifice that you currently urinate through. So just a couple other pictures in case these make more sense. Again, you kind of sew the back wall together, then you fold it on itself to make a circle, then there’s the ureters coming down, they drain into this reservoir and then this goes out through the natural pelvic floor.

Bowel, as I just sort of alluded to, is not meant to be in contact with urine. Postop, one month after any of these surgeries, 30% of neobladder patients were quite acidotic meaning their body pH was less than 7.4. It can be in the 7.3, 7.4s and we sometimes have to supplement that. Much less common in a conduit because that urine is just sort of traversing through. That’s a long term problem at a year, still up to 25%, the neobladder and 10% of the conduit.

So again, you might need extra vitamins, you might need to take some bicarb or citrate. There might be things we have to do to adjust that body pH. If your bicarb in your blood is less than 15, you do need supplementation. And these are… if your filtration rate is not good before surgery, meaning you don’t have good kidneys before doing that, we classically are taught that that’s not a good person to do this continent bowel reservoir because the electrolyte abnormalities are going to be very difficult to manage because the kidneys are what’s trying to keep up with those electrolytes, so something to think about.

Dr. Tracey Krupski:

Even kidney failure can happen in up to a third of muscle invasive bladder cancer patients right after these surgeries and your kidney function will continue to decline for years afterwards again, because we’re putting some stress on the kidneys by having this urine be in contact with bowel. Metabolic acidosis, the reason you don’t just want to run around with a chronic acidosis that I’m talking about is it can start to chew up your bones.

It tries to offset that bicarb loss by taking bicarb out of your bones. It’ll make any kind of diabetes or endocrine problems with sugar worse. It will accelerate kidney disease. It will cause muscle wasting. You’ll lose the albumin in your bloodstream. So gain, not great to stay in an acidotic state so we do need to treat that, you can’t stay like that. And magnesium phosphate, I just sort of alluded to calcium wasting due to the bone. So again, this is serious, we do have to follow all these things postop.

You don’t want to do any kind of neobladder in anybody with cirrhosis, that’s sort of just an extra tidbit, not the focus of this. So… Ooh, that was already a lot but this is where you should really be meeting with your urologic oncologist two or three times before undertaking the surgery because this is not the kind of information that you can go into one visit and have everybody tell you, well, let’s talk about removing your bladder, doing chemo radiation, and do you want chemotherapy?

And oh, by the way, the surgery’s really complicated and this is all that’s going to happen. This has to be done in stages and given time to process it and come back, ask your questions, think it through because it is a major life changer and a major surgery. So this is just a person, a man from the side and just showing you that the bladder gets removed, the prostate gets removed and the seminal vesicles. If you’re going to do a neobladder, you would sew to this urethra and they would still be able to urinate here.

It’s showing how close it is to the rectum. That’s another area we worry about and how your vas deferens will be clipped to do the surgery. Then the bladder’s removed, it’s hiding behind the pubic bone, so that’s what this is showing. Again, these are all areas where the surgery is complicated. The kidneys have to be rerouted into this piece of intestine. These are some actual photos of things.

Dr. Tracey Krupski:

I don’t want to dwell on how we would do the surgery, but it could be done robotically through some small ports but the bladder has to be removed somewhere. So there is an incision to get everything out. This is just a little shot of the robot. The old fashioned way I haven’t seen… I’ve never made one above the belly button. Mostly it’s a incision from the side of the belly button down that does the same thing that the robot does.

This is a person showing their incision. This is more like it where they have some kind of continent diversion. This is the incontinent conduit so you can see the urine’s just draining straight into a bag on their skin. And this is the second belly button I was talking about where you will put a tube in through the skin forever more with a continent diversion. So ileal conduit, urostomy is this one. That’s the same thing, it’s just two words for the same thing. Neobladder, this one, he must be hooked up to his natural orifice. Continent pouch is this one where you can see the second belly button at the skin and you’re putting that tube in through that bowel, and that’s what will drain the urine. So just to give you a little bit of a thing. The complications are extreme, the list as long as my arm. All kinds of stuff happens after this surgery because of what I just talked about. We’re working on a lot of different areas, we’re working on a lot of things and you have to be aware of these complications and what to look for in the postop period.

So I just wanted to touch on this was a study that we were part of. It was a United States study and they looked at complications after surgery. We did 15 centers in the country. The patients, we let a coin, it was a computer decide if they were going to have it done with the robot or have it done the old fashioned way. And what I wanted to tell you was the complications, whether you were at Mayo Clinic, Vanderbilt, UVA, UCSF, Harvard, Scottsdale, Cleveland Clinic, it’s a big surgery and they had adverse events, meaning some complication in 67% of the robotic cases and 69% of the open cases, so very high.

Dr. Tracey Krupski:

The length of stay, how many days we’re in the hospital. It was six for the robot and seven for the open cases and the cancer survival or the cure was the same, essentially 72.3 versus 71.6. So the robot doesn’t make it better, the robot doesn’t really change your complications. It doesn’t change your length of stay that much. It’s fine to use it, I’m not against it, but you still have complications regardless of how you do the surgery. The surgeon is still doing the surgery and has to do all the appropriate steps.

This is that long list of things I just told you about. What I wanted to pull out of that is that ileus means your bowels slow down. Bowels don’t like being taken apart and put back together. So you’re in the hospital those five or six days while we wait for your bowels to wake up so you can start eating again. Infections were really common in this group. Again, this is data from 15 centers across the country, all the best places, it’s just a complicated surgery.

Infections of the urinary system, infections of the bloodstream, scar tissue between the kidney and the intestines where we sewed that ureter together, atrial fibrillation or heartbeat irregularities, blood clots that go to your lungs or your legs, so these were all fairly substantial and 25% of people got readmitted at all these good places. So I am not trying to tell you not to do the surgery. What I am telling you or what I tell my patients is that we need open lines of communication and you need to be prepared to let us know if these things are happening.

They are all fixable. We can fix them, but the sooner we know about them, the sooner we can fix it. And if you need to come into the hospital to just get through it, let’s come into the hospital, get through it to get you back on your journey and get you back to normal life. You’ll read a little bit about enhanced recovery after surgery. It’s a multimodal pathway. We’re getting rid of opioids, we don’t leave tubes down your nose anymore. We let you drink Gatorade before surgery. We don’t wash out your entire intestine and make you start out dehydrated.

Dr. Tracey Krupski:

So it really has streamlined recovery and it has minimized the very severe complications after surgery and most people will do an ERAS type pathway. These are sort of the highlights that you may have heard something about. We don’t do a bowel prep. It’s not like a colonoscopy, you don’t have to drink all that stuff and make yourself… have defecate clear liquid. You usually use boosts, nutrition, Gatorade right up to two hours before surgery. We don’t use epidurals in your spine anymore.

We’ll give you multiple pain medications that are not opioids so that we can try to get your bowels working sooner, eat more quickly. And you get educated about all the steps that are to be expected. And most of these will give you fluids at home. So when you go home, we will set you up to have fluids two or three times a week to keep that hydration, keep those electrolyte problems at bay while you’re getting stronger and getting back to your normal self.

You’ll get these workbooks, worksheets. Again, it’s all about what we expect and what you should expect so that you know when to contact us.

Dr. Tracey Krupski:

You may have a diversion plan that you want the neobladder, but you sometimes have to change during the operation. We may say that there’s cancer going into the urethra or the intestine doesn’t reach so we can’t do a neobladder. If there’s a cancer at the margin, those will be reasons not to do it. Again, if you don’t want to potentially catheterize yourself or at least be willing to learn just in case, that’s going to be a questionable person to do a neobladder on.

If you already have inflammatory bowel disease or problems with digestion and nutrition, we may not want to use two or three feet of your intestine to sew in to this circle to be your reservoir. We always do a node dissection. This is kind of to be just quickly, but we will take all the nodes next to the ilea and artery and vein going down to this obturator nerve all the way up towards the iliac bifurcation. So that’s what we’re showing here. At least these lymph nodes on the right pelvis and the left pelvis, some people even do an extended node dissection all the way up to the cava. That’s more surgical than you probably need to know.

Dr. Tracey Krupski:

Quality of life. So what happens after this surgery for muscle invasive bladder cancer? So when people talk about quality of life, when I did a lot of health related quality of research in my fellowship, we talk about these domains of health related quality of life. What are your limitations due to your emotional problems from having this surgery or physically you just can’t do things anymore. That gets to your mental health, your social functioning.

Can you still be a dad? Can you be a wife? Can you be a husband? Can you do those roles that you used to have in your life, a teacher, et cetera? Do you have chronic fatigue? Are you in pain? So these are all health related quality of life and we consider it kind of six or seven domains of quality of life. When we look at this, it’s very different. There’s no clear best choice that I could tell you everybody with the neobladder has a great quality of life or those people who got a conduit never had any problems.

We have to think about things like your dexterity, arthritis, catheterizations, those things, it’s very personal. And going through, this is going to be like a prostate surgery. It’s going to change your sexual functioning. It’s going to change your orgasm sometimes. You might have incontinence if we build you this new bladder. You’ll have incontinence occasionally even if you have the bag. So these are all going to be new life considerations that you probably haven’t had to work with right now.

This was that same RAZOR study that we looked at neobladders and conduits and all those different quality of life. There’s physical wellbeing, social wellbeing, emotional wellbeing. I’m sure you can’t read the slide, but the point of it is all of them declined from baseline over the first six months. So there’s a lot of dealing, learning to emotionally deal with getting through the chemo, getting through the surgery, dealing with your new bladder or pouch, however you want to think of it.

Dr. Tracey Krupski:

And the quality of life changes. We’re a little bit more severe for the neobladders than they were for the diversions. But either way, there’s a decline in your quality of life and that still hasn’t bounced back even six months later so you just have to be ready for that as do your caretakers. Then you might even need extra therapy after cystectomy.

 So you’ve done everything we’ve told you, you’ve done the neoadjuvant chemo, then you’d get through the surgery, you get through all the complications. And we may still tell you we want to give you extra immunotherapy or these new drugs that are called antibody drug conjugates. So again, there’s new data that if your nodes were positive at the time of surgery or we had positive margins, you may want to take an additional therapy to again, extend your survival. And you’re like, “Geez, how many more things could I go through?” So it is a journey, that’s why I use that word. So this was kind of summarizing the treatment algorithm we’ve been through.

And then the only other thing I just wanted to talk about quickly was you do need to be monitored after this surgery. You need a chest x-ray, CT scans, labs, all that stuff has to be done at six months to 12 months intervals at a minimum for three years, most of us will follow longer if we can. And then if you have your urethra still that’s in contact with those urine cells so that we may have to have washings done. The newest thing that I wanted to talk a little bit about is the role of genomics.

Dr. Tracey Krupski:

This was the Cancer Genome Atlas, and I’m just going to speed through. It’s one of those huge projects that 2005, the NIH started looking at the genes related to the individual cancers. And around 2010 and 2009, we start to look at urothelial cancers. And we find that urothelial cancers have mutations in 32 different genes and nine of those have never been reported in cancer before. So why that’s exciting is it gives us new targets for treatments that might be curative and we can look into their RNA sequences and the proteins that these genes make and again, develop new targets.

And we found that we could classify these cancers into these basal genes that get turned on p53-like or luminal and where this is going now in the modern age is we can use that data to run a bladder decipher test. Like you could do a genomic subtyping of your individual tumor and see which of those genes was turned on which tells us if you’re going to respond to chemotherapy potentially. So this hasn’t been prospectively validated, but this is the idea, we send the tumor off from your endoscopic procedure and we can say, this person has a basal genomic subtype which would do great with this platinum based therapy. They should get the chemo because they’re totally going to respond.

These would be considered for intermediate immediate surgery because we don’t think chemo’s going to work as well. So this is sort of brand new stuff that we’re working into how we treat people now, and I think it’s going to change how we can personalize the medicine for you going down the road. It’s not quite prime time, but it’s coming. So I just wanted to, again, end on more of a high note.

Dr. Tracey Krupski:

And again, these are these different subtypes and this shows at the very bottom which of these drug targets there could be. These are good immunotherapy. They don’t respond to cisplatin. These look like they would work for ifosfamide. So thank you for your attention.

Morgan Stout:

Thank you so much, Dr. Krupski. That was very thorough and we’re so glad that you were willing to do this. We do have a couple of questions. And just as a reminder, if you want to put your questions in the Q&A box. If you put them in the chat box, it’s a little harder for us to keep track of so put them in the Q&A. So our first question has to deal with chemotherapy. What are the decision points for a urology team on deciding with a patient with muscle invasive bladder cancer whether to do a dose dense MVAC versus GemCis versus straight cisplatin. Can you talk about that a little bit?

Dr. Tracey Krupski:

Sure. Great question. A lot of that comes down to the medical oncologist preference. Now I will tell you the actual evidence for the neoadjuvant chemo was for dose dense MVAC. So dose dense MVAC was what was done in the trials. And that had the 5 to 8% overall survival, better for T3 disease, that type of thing. However, when they tried to compare the two in the after setting or in other drug combinations or other cancers GemCis, the Gemcitabine with cisplatin seems to be equivalent.

The dose dense MVAC is also much harder on a patient. It has cardiac toxicity. So because we think they’re fairly equivalent and there’s less toxicity, many oncologists will just give the GemCis. And that’s what I see more often in our communities, but by no means would dose dense MVAC be wrong. It’s just a little bit harder for the patient to get through.

Morgan Stout:

Thank you. Thank you for that. Our next question is about going back to that chemo radiation topic. There was a question about confirming chemo radiation that a third of patients will be cured, another third will still need to have their bladder removed and the final third will not have a positive outcome. Can you talk a little bit more about that and just kind of…

Dr. Tracey Krupski:

Well, to frame that versus surgery, what I will tell people the third, third, third can be a little bit complicated. But if you just walked in the door, I would generally say if you do surgery alone, you have a 65% chance of being cured, meaning your cancer doesn’t come back and you don’t need any more therapy and we gauge that at the five year time point. If you do chemo radiation, I would quote you 40% chance that you will be alive without cancer in five years with your bladder. If you add chemotherapy to the surgery route, that’s where I would prove be more like 70, 75%. So generally, it’s 40% of people are cured and they don’t need anything else for their bladder cancer if they do chemo radiation. I will say within the first two years is when you fail. So those office cystoscopies that are done after chemo radiation, if we find active bladder cancer, we would recommend then that you go to cystectomy at that time again, if you are a surgical candidate.

So although the third, third, third makes it sound like it’s going to progress, the cystectomy people have a third of the cancers coming back too even though you went through all the trouble of getting your bladder removed. So that’s where it’s a very serious disease. That’s where we get that because those numbers are not good. I mean, I don’t want to tell any family those numbers, but those are the real numbers.

Morgan Stout:

Absolutely. And that’s super informative. Thank you. So let’s talk a little bit about side effects. You had that big long list and this question was dealing specifically with lymphedema after a radical cystectomy with the lymph node excisions. How often does that happen and, or what are the other probably top two most common side effects?

Dr. Tracey Krupski:

Well, lymphedema would not be one of them. Lymphedema is pretty rare. Usually the pelvic lymph node has enough cross drainage, meaning the inguinal nodes, the ones right under your skin of the groin can usually pick up the slack from the move of the bladder, the prostate, there’s sacral lymph nodes, there’s other lymph nodes that usually do the job. So I would wonder if there had been either radiation for some other reason that might have impaired those other lymph node, drainage that led to chronic lymphedema or occasionally not usually a nutrition thing, but maybe the surgeon did an extended lymph node dissection, meaning they took a lot more lymph nodes than those ones that I briefly showed in the pictures, those could relate to lymphedema. I think the most common problem after the cystectomy in general, if I’m interpreting the question right, is kidney infections. It’s pyelonephritis. It’s recurrent kidney infections because the urine is not able to drain quite as quickly as it used to either because there’s a little bit of scar tissue where we sewed the intestine to the ureter or sometimes it’s just lost the elasticity. There’s a peristalsis that gently pushes the urine from the kidney out of the body. And if that’s lost, you can have stagnant urine.

And I’d say kidney infections are the most common long term one that we have to be dealing with along with scar tissue. The fortunately slowing down of the bowels is the other big one that keeps people in the hospital. But once you get through those two or three weeks post-op, most of all that you get through it, it’s gone, you’re just watching for kidney infections and electrolyte abnormalities.

Morgan Stout:

Absolutely. Another question we had was talking about that genomic testing. What kind of genomic testing do you do and is it covered by insurance?

Dr. Tracey Krupski:

So I will tell you that the companies are just coming online. The main one I know about is the Decipher, that was the one shown in the slide. I do not work for Decipher, I’m not promoting Decipher. But what those genomic tests will tell you is they will cap it at $200 out of pocket for most patients. So while they might charge insurance X amount, certain insurances will cover it. I don’t think Medicare is now, but don’t quote me on that. But as far as out of pocket for the patient, it’s usually only $200.

Morgan Stout:

Thank you. This question has to do with adjuvant chemotherapy. If chemotherapy wasn’t done after radical cystectomy, can the same type of cancer return or would you see a different type? And can you use chemo and radiation for a different type of cancer that comes?

Dr. Tracey Krupski:

So couple pieces to that. So we just talked about you could do surgery and a third of the time maybe the cancer, urothelial cancer, meaning bladder cancer will come back. If bladder cancer comes back in a lymph node or a bone or the liver, you can use the same chemotherapy again that you used pre, so a cisplatin based chemotherapy, again, with the caveats that your body can tell your kidneys are okay.

You also can do immunotherapy now. So those are, you sometimes see it on TV, nivolumab is advertised as KEYTRUDA. Those can be given if the cancer has come back after surgery and then you might use chemotherapy, but you might actually moving towards immunotherapy now, things like ipilimumab, nivolumab, atezolizumab, all these lalamabs, but they’re immunotherapy. As far as radiation goes, you can radiate again, but not the same spot. So say somebody had colon radiation, so they had pelvic radiation for a colon cancer. We couldn’t radiate the pelvis again because there would be too much radiation toxicity to the tissues. But if you did chemo radiation for your bladder and then you had a spine met way up here, meaning cancer, bladder cancer in your bone, we could radiate that area again to control the tumor or get rid of pain. So yes and no, if that makes sense.

Morgan Stout:

Absolutely, it does. I think we have time for one more question. And this one just popped out at me. I have a muscle invasive bladder cancer diagnosis, but I haven’t started any treatments yet. Why do I feel terrible?

Dr. Tracey Krupski:

Well, I will say that it’s probably because there is tumor. Even though they’ve resected and we do our best, sometimes there can be tumor underneath the surface, there could be tumor in other parts of the body or other parts of the bladder underneath the surface that the urologist could see. My experience, so there’s a couple things, A, you’re bummed. I mean, you’re not happy. This is not a good disease to be told about. Your body is stressed emotionally because you’ve been told this diagnosis, and that’s hard. I mean, the whole body’s responding to bad news, so to speak. Two, your own immune system, whatever microscopic cells underneath the muscle layer that we might not see, whatever tumor is there, your own immune system is spending all its energy trying to keep that in check and you’re probably still recovering from this surgery where we scrape out the bladder and that makes you have burning and irritation and blood and frequency and not sleeping well because you’re getting up to go to the bathroom all the time and kind of standard urology things, unfortunate, but true.

I have found that when the people start chemotherapy, a lot of people, especially if there’s pain, if you’re still having pelvic pain with extensive sitting like behind the scrotum or by the vagina, a lot of that will get better with chemotherapy. And honestly, when it gets better with chemotherapy, that is a great sign that the chemo’s working, that you’re going to do pretty well with surgery that will be able to get rid of everything.

So that could be a long-winded answer to I’m sure it’s multifactorial. I mean, there’s a couple different things going on. And the biggest thing we could tell people is nutrition, nutrition, nutrition. I mean, the best protein, vegetables, boost instant, Carnation Instant Breakfast, anything that can get you calories that are not just Twinkies or macaroni and cheese, which I like macaroni and cheese like anybody, comfort foods, but getting really good nutrition would be one thing that you could do straight up that you have control over so to speak.

Morgan Stout:

Absolutely. Well, thank you so much for your time, Dr. Krupski, it was a phenomenal program!