Managing a Bladder Cancer Diagnosis

Dr. Bernard Bochner:  Welcome to this special information session on bladder cancer. I'm Bernard Bochner, Urologic Surgeon here at Memorial Sloan Kettering who treats patients with bladder cancer. I'd like to thank you all for joining our session today. We've put together a panel of experts, people who deal with bladder cancer patients on a daily basis to answer some of the common concerns regarding the diagnosis of bladder cancer, the treatment of the disease, and to highlight some of the interesting research opportunities in regard to bladder cancer for the future. I'm joined today by an expert panel, including Dr. Jonathan Rosenberg, the Chief of Genitourinary Medical Oncology here at Memorial, also Medical Oncologist, David Aggen.

Also joining me are Urologic Surgeons, Tim Donahue and Eugene Pietzak. We also have our Wound Ostomy Care Nurse Specialist, Vashti Livingston who would be able to address some of the support related questions regarding bladder cancer following treatment. Before we get started with the panel, I'd like to introduce a few facts about bladder cancer. Commonly people want to know how they got it. What causes bladder cancer? Bladder cancer is an exposure related tumor. Something in the environment that people get exposed to gets into the system, probably about 60% of bladder cancer is smoking-related, tobacco-related, but there's also environmental exposures and occupational exposures, chemicals that get into the body. The body tries to filter those chemicals away through the kidneys into the urine as a way of getting rid of it. It's a good way of getting rid of things that our body doesn't want. The problem is, is that those chemicals are then concentrated within the urine and these chemicals are then exposed to the surface of the lining of the drainage system. Anywhere along the drainage system damage can occur because urine is stored in the bladder for hours at a time, the bladder gets the biggest exposure to these, potentially carcinogenic chemicals and therefore bladder cancer can develop and is about 10 times more common than urothelial cancers of the rest of the urinary system.

There's a variety of potential occupations that may be related chemicals, people who are in the chemical rubber dye, manufacturing industry. People who may be exposed to large quantities of diesel fumes, things like that. But there's also a variety of exposures that we just simply don't know about. There may be a familial predisposition for some people to get bladder cancer and there may be a role for genetic testing that I think some of our panelists will also address. How do people know if they have bladder cancer? Well, in general, people will present with some painless blood in the urine. They may see it and it goes away for maybe several weeks before it returns. Sometimes it can lead to a delay in the diagnosis of the disease as well. Some people will have a mass identified within the bladder and imaging for some other purpose and less commonly, but occasionally people will have changes in their voiding patterns, which may actually represent an underlying problem like bladder cancer.

It's important to recognize that bladder cancer is not a single disease. We're going to highlight that for you. Probably the most common form of bladder cancer is a non-muscle invasive form of the disease, starts on the lining and it stays confined to the lining, the inner lining of the bladder. Some of these tumors will also present as an invasive form where it can invade into the deeper parts of the bladder wall. They can be more dangerous, and their treatment is different. Based on that greater concern for spread rarely, but occasionally people will present with more advanced disease where the cells have gotten outside the bladder and moved to other parts of the body. And there is a subset of folks who start with localized bladder cancer, who may recur following treatment and may require additional therapy.

So, let's get started with our panel. We're going to bring in Dr. Eugene Pietzak and Eugene, could you give the folks a little bit of an understanding about how bladder cancer is diagnosed, and the procedures associated with them?

Dr. Eugene Pietzak:  Sure. Thank you, Dr. Bochner. I think probably the most common procedure that is performed in order to diagnose bladder cancer. It is typically either an office cystoscopy, which eventually leads to an endoscopic procedure that we generally do under some sedation, some anesthesia called a transurethral resection of bladder tumor or TURBT. I generally describe it to my patients as being a bladder scraping. So, lot of the patients sleep under anesthesia, you take a look around the entirety of the bladder, any abnormalities, get biopsied and assessed. And it's a commonly performed procedure that is typically associated with some urinary light side effects afterwards, some irritation, urgency, frequency, very frequent to have blood in the urine.

 

Usually, it's very self-limited and only lasts for a couple of days. Typically, we try not to send patients home with a urinary catheter after the procedure, but sometimes that is required, especially if there's multiple tumors or multiple or large tumor that needs to be removed. And we're looking to get a good amount of deep muscle sampling. In select cases, particularly if someone has a low grade, less aggressive appearing tumor, sometimes we'll give a one-time dose of a chemotherapy agent directly into the bladder and that's more of a bladder wash. It does not get into the bloodstream and it doesn't have those associated side effects that people typically think of with chemotherapy but that's a on a case-by-case type basis.

Dr. Bernard Bochner:  So, let's be clear then just to clarify patients are asleep for these procedures, right?

Dr. Eugene Pietzak:  Certainly. Yes.

Dr. Bernard Bochner:  And do they typically stay overnight on these outpatient type procedures?

Dr. Eugene Pietzak:  These are typically performed on the outpatient basis. People are usually going home a couple of hours after the procedure.

Dr. Bernard Bochner:  Excellent. Okay. And then once the tissue is removed, it'll take a few days, a pathology report is made available. And then if this report comes back and the bladder cancer diagnosis is made, but it's a non-invasive form of the disease. Can you give folks a little bit of understanding what is non-muscle invasive bladder cancer? What usually follows after that diagnosis?

Dr. Eugene Pietzak:  Yeah, so non-muscle invasive bladder cancer, historically used to be called superficial, although with greater understanding of the biology of the cancer itself. We designated it a little bit differently now because some non-muscle invasive tumors actually behave aggressively or most of them the treatment since they're confined to these the superficial layers of the bladder. Many of the treatments can be directed into the lining of the bladder itself and that's usually done on the outpatient basis a couple of weeks after the scraping and those treatments are instilled typically into the bladder directly through the catheter. And so, the most common agents are these chemotherapy agents, or an agent called BCG, which is actually a live but attenuated bacteria that provokes the body's immune system to fight off cancer cells.

Dr. Bernard Bochner:  And so, it sounds as though these tumors can come back in the bladder and maybe you could just give folks a little bit of a sense as to how common is that? Do they all come back as the same non-invasive tumor? And how do we pick up these recurrences?

Dr. Eugene Pietzak:  Yeah. So, we think that bladder cancer actually has one of the highest recurrence rates of all cancer types. Fortunately, most of the non-muscle invasive recurrences reoccurred also superficially, although unfortunately not always but we want to keep a close eye on these tumors since they're at such high risk of coming back. So, what we will typically do as urologist is we will see patients back in the office for an endoscopic procedure when they're awake in the office. And that is an office cystoscopy, which is a small camera that is inserted into the bladder to surveil around, take a look around to make sure that none of these tumors have come back and so the frequency at which we do that varies depending on how likely it is that the tumor will actually come back. But we're also working actively as a group to come up with non-invasive urine-based biomarkers that hopefully either replace or assist in the detection of these recurrent tumors.

Dr. Bernard Bochner:  So, most people should expect some form of intravesical therapy either right around the time of the transurethral resection or after the diagnosis is made and then follow up, everybody gets followed up, is that correct?

Dr. Eugene Pietzak:  In the setting of a malignancy, yes, some degree of follow-up and that frequency of follow up, the surveillance cystoscopy really depends on the likelihood of the tumor coming back and how aggressive the tumor is.

Dr. Bernard Bochner:  So, you mentioned nicely that there's several forms of intravesical therapy, including chemotherapy and BCG, which is a form of immunotherapy as you mentioned. But despite this, it sounds as though there is still a significant percentage of folks that recur, what happens after standard intravesical therapy? Is there hope that people will be able to have some additional therapy after that?

Dr. Eugene Pietzak:  Yeah. So, what's interesting is BCG has been clinically used for several decades now and even though it is a bacteria, it works really well in most cases, although recurrences are unfortunately all too common. And so, there are very few effective treatment options in the setting under recurrent tumor after BCG and collectively as a group as you know, we were participating in several clinical trials and several efforts to come up with either alternative treatments to BCG, ways to make BCG more effective or alternative options after recurrence occurs after BCG, because in certain patients who have recurrences that are not responsive to BCG, meaning they quickly come back after in an aggressive form. Oftentimes those patients are recommended for bladder removal for radical cystectomy, which Dr. Donahue and I'll be discussing later on. But obviously we're all working towards coming up with more effective treatments that can offer an alternative to bladder removal for those patients that have non-muscle invasive bladder cancer recurrences.

Dr. Bernard Bochner:  Yeah, and I think that it's important for folks out there to hear that this is one of the most exciting times in bladder cancer research. There is now more options and a large number of trials of novel agents that we're very hopeful is going to offer us some additional support for the non-muscle invasive patient. Dr. Pietzak, thank you so much for that. I wanted to bring Tim Donahue in here. Dr. Donahue, can you give us a little sense about the differences and the clinical importance between a non-muscle invasive and a muscle invasive tumor?

Dr. Tim Donahue:  Thanks, Dr. Bochner. As Dr. Pietzak had pointed out, bladder cancer comes in basically two different forms. You have your non-invasive form and then your muscle invasive form. And the reason why we differentiate between these two is that as Eugene had pointed out, when you have superficial disease, often a scraping and a topical management is adequate to control it and prevent future recurrences. But if it's invasive deeply into the bladder wall, topical therapies won't penetrate to that leading edge and can't take care of the deeper component. And for that reason, we have to think about managing the bladder differently. We also know from our experience with patients that about halfway through the wall of the bladder are blood vessels and lymphatic channels. So as a tumor penetrates deeply into the wall of the bladder, it can have access to blood vessels lymphatic channels and potentially move beyond the wall of the bladder to other sites. So, when a patient has muscle invasive bladder cancer, we think of it as a disease, both within the bladder that has to be managed, but also outside of the bladder say in the lymph nodes. And this is where our collaboration and coordination with our medical oncologist is so important. Dr. Rosenberg is going to talk about the role of chemotherapy or immunotherapy for patients around the time of this diagnosis and how it improved the survival.

Dr. Bernard Bochner:  Tim, it sounds like the depth of invasion then is quite important to establish and then obviously this means that the transurethral resection has to provide certain information to be able to help guide you and then guiding patients, correct?

Dr. Tim Donahue:  Absolutely and so when we go in and do a resection of the tumor, we're looking at different pieces of information to help us tell, we want to know the type of tumor because as you stated, there are many types of tumors that can grow in the bladder and some subtypes can have a more aggressive potential. Our pathologists are excellent in trying to delineate which type of tumor it is. The grade of the tumor can tell us a lot about behavior and the depth of involvement is exceptionally important in determining how we manage patients next.

Dr. Bernard Bochner:  So, these tumors obviously have a potential for spreading and therefore are more dangerous than the non-muscle invasive tumors. Can you just speak to what the key components then for the treatment of a muscle invasive tumor are? What can patients expect?

Dr. Tim Donahue:  So, for patients with muscle invasive disease, what we've learned from all of our experience over the years is that removal of the bladder offers the best long-term outcomes. It gives the best cancer control because the lining of the bladder has some potential for recurrence and if you deal with tumor one now you may be at risk for tumor two down the road. So, this is often why we recommend bladder removal. In some circumstances we can move a portion of the bladder and in some patients, there may be an option for bladder preservation through radiation treatment, but the gold standard is still bladder removal and that's an operation that can be done either through an open or robotic approach. And once the bladder and the adjacent organs are removed, then we have to reconstruct the urinary tract.

Dr. Bernard Bochner:  So, Tim, this obviously sounds it is a major procedure. Give folks a sense about how common this is done by just the general urologists and maybe what should people be looking for when they're trying to decide about where to get this type of complex treatment?

Dr. Tim Donahue:  I think that's an excellent point. When we look nationwide, half of hospitals do three of these bladder removals per year or less. Half do more than that. High-volume hospitals consider to do more than 10 bladder removals per year and a very high-volume hospital might do 20. When you come to a place like Memorial, where we do 10 times that number at least per year, that's where we're able to really kind of garner the resources to optimize the outcomes. All of the studies that are out there that look at volume for cancer surgeries kind of point out that major surgeries like this, bladder removal, major pancreatic surgery, major lung surgery, they all do better, patients do better over the long run when they have it done at a high-volume facility. And it's not just the surgeon, it's the anesthesiologist who are familiar with this. It's the nursing staff on the ward. It's the wound ostomy nurse that's able to care for the patients. It's the pathologist who's reading the specimen. It's that entire group. And as I tell patients all the time, you could take me or any of the surgeons here at Memorial and put us in a different facility and we wouldn't be able to render the same care it's because it's the entire group that comes together to provide this for the patients.

Dr. Bernard Bochner:  And so, Tim, it sounds as though high-volume centers and high-volume surgeons have lower risks of complications and patients tend to do better in that setting. Give us a sense then as to sort of the full extent of the procedure, what can men and women what would  they need to be prepared for? What comes out, what needs to be done?

Dr. Tim Donahue:  In a man, the bladder and the prostate are removed as one unit and that's because frequently the prostate or the lining of the urethra, as it goes through, the prostate is involved with this type of cancer. And so, we take that out as one unit, we take out the lymph nodes that surround the bladder. In women, we often will remove the uterus and the ovaries at the same time, although there are some circumstances where uterine sparing or vaginal sparing can be performed. Again, the lymph nodes are removed because we found that by removing the lymph nodes, patients have a better long-term cancer outcome as well and this can also be very therapeutic. It can also tell us more about the patient's risk of recurrence over the long run.

Dr. Bernard Bochner:  And we're going to talk to Vashti Livingston, as far as the support goes afterwards in particular, with respect to urinary diversion. But I think your point is important to highlight, which is that quality of life after these procedures is actually exceedingly high. Patients get back to doing all the things that they want to do. We pay particular attention to things like urinary functional preservation, if possible, maintenance of sexual function afterwards, when possible, as well. And these are all important things I think for folks to be able to discuss with their individual physicians. So let me bring in Dr. Rosenberg then. So, Jonathan, obviously these are high risk tumors and local therapy like surgery may be effective in many patients, but because of this risk of spread we obviously have to combine the medical oncology group. Can you explain the role of pre-treatment in muscle invasive disease? Why do patients need it and what exactly are they going to get?

Dr. Jonathan Rosenberg:  Thank you, Bernard. It's a pleasure to be here today talking to you. We know that potentially up to 40% of patients have a microscopic metastasis at the time that they present for treatment of their muscle invasive bladder cancer. Most patients are at very high risk for recurrence after surgery. People think, well, you took out my bladder, where's the bladder cancer coming from? Well, it's probably out there somewhere in many patients following surgery, but there's no tests that we have in 2021 that can actually detect it. And so, the strategy is evolved to administer chemotherapy before surgery in patients who are able to tolerate a medicine called cisplatin, which is a toxic medicine for some patients but well tolerated in others, can affect the kidneys, the hearing and just general function. And so, patients who are healthy enough to receive it should receive several months of chemotherapy because we know that many of those patients the chemotherapy will sterilize those cancer cells elsewhere in the body and eliminate them and actually increase the chance that a patient is cured of their cancer once they have their surgery.

Dr. Bernard Bochner:  So, Jonathan, if we can't see these cells, it sounds like these are microscopic cells that are out there not going to be picked up on standard imaging, then how do you decide who's a candidate for chemotherapy then?

Dr. Jonathan Rosenberg:  So, this is where we have to individualize our treatment recommendations based on the patient who's in front of us. An 85-year-old person with bad medical issues may not be a great candidate to get this type of chemotherapy and still may be able to undergo surgery. Whereas a younger fitter patient who has adequately functioning kidneys, no major hearing issues, no sensory neuropathy, which means numbness and tingling in the fingers or the toes and no major heart issues, those people can receive this type of chemotherapy. We also know from a lot of data that if we can't use a medicine called cisplatin, it's probably not worth giving because the effectiveness of other chemotherapy drugs in the absence of cisplatin is not so good. And so, while we do give combinations with cisplatin, cisplatin has to be part of the mix. It can't be carboplatin or Taxol or other chemotherapies by itself.

Dr. Bernard Bochner:  Jonathan, obviously it sounds pretty serious here as far as the treatment, but can you give folks a sense as to just how important these medications are? I mean, what benefit are they getting from receiving this pre-treatment?

Dr. Jonathan Rosenberg:  So, this pre-treatment therapy based on the clinical trials that we've seen reduces the chance of dying of bladder cancer by about roughly one third and that's a really substantial number. It is essential for patients who can get it but it's also essential not to give it to people who might be rendered very, very sick and very, very ill, and actually not able to undergo surgery.

Dr. Bernard Bochner:  So, what do you do in that setting where somebody presents with a muscle invasive tumor, but maybe their kidney function is not great or they've got some hearing loss related issues and you're concerned about giving these medicines, which sound very effective. Do they go right to surgery or are there some other options?

Dr. Jonathan Rosenberg:  There are so yes, and yes. So, they often go right to surgery. Sometime we look for reversible reasons of kidney dysfunction if someone has a blocked kidney from a tumor, we can do something they are called placing a percutaneous nephrostomy, which is an external urine drain and often the kidney function will recover in that situation. But in general, moving right to the operating room is a very good approach for those patients. However, we think that systemic therapy before surgery is a good thing in general and we actually have a very active clinical research program trying to investigate new treatments that might eliminate and eradicate those micrometastasis with treatments that are very different than cisplatin-based chemotherapy. So, we have trials testing immunotherapy as preoperative therapy, both for the bladder and as well as upper urinary tract tumors, tumors that arise in the kidney and the ureter. We're testing novel types of chemo drugs in that setting as well, a drug called Enfortumab Vedotin in an upcoming trial for upper urinary tract tumors prior to surgery. And so, we're looking at options to really identify how well they work. So, we can take them to larger trials to see whether or not we actually increase the cure rates because that's the real goal here. And there are patients who can undergo chemo radiation as an alternative. And we always review that option with patients because there are some bladder sparing options that can be particularly good for certain patients. And there are some patients where surgery is not a good idea and maybe that's a better approach to try to treat their cancer with the hope of curing it.

Dr. Bernard Bochner:  Can you give folks a little bit of a sense, you mentioned immunotherapy and obviously there's a lot of information out there. What is immunotherapy? Can you give folks a sense as to what that is?

Dr. Jonathan Rosenberg:  So, there's a lot of different ways of thinking of immunotherapy, but essentially, it's harnessing the immune system to kill the cancer cells rather than using drugs to directly kill the cancer cells and the types of immunotherapy that are in common use or in clinical trials tend to be antibodies targeting different molecules on the immune cells that are inhibiting the immune system from recognizing cancer. And so, when you target the things that are blocking the immune system, you relieve that block and hopefully the immune system will recognize the cancer and attack it. They haven't proven to be as revolutionary, I would say, as we had hoped. For some patients, they are incredibly powerful medicines and you'll hear probably a little bit about that from one of my colleagues in a few minutes. But they're not at the moment yet ready for prime time in muscle invasive bladder cancer. The data just are not as compelling to say we can give you immunotherapy to the average guy and not end up having to take out their bladder because that's something I hear from patients. Can you just give me an immunotherapy and I don't have to worry about getting my bladder out? We're not quite ready to go there yet.

Dr. Bernard Bochner:  And obviously everybody, if it's safe, would like to try to preserve their bladders, if possible. Can you tell the group a little bit about some of the advances that are happening at Memorial with respect to bladder preservation and patient's genetics? How is that coming into play?

Dr. Jonathan Rosenberg:  There are patients whose tumors harbor mutations within the tumor cells, not within the rest of their body, generally that affects the ability of the cancer cells to repair their DNA and presumably there's the fitness, there's a reason why those cancer cells have these mutations, but it actually creates a susceptibility we think to chemotherapy and maybe radiation. And so that those patients have tumors that we think and have shown are exquisitely sensitive to chemotherapy and in the presence of those mutations we think that the outcomes with chemotherapy might even allow us to avoid radiation or bladder removal in a select group. And so, there's a clinical trial sponsored by the National Cancer Institute run by one of my colleagues nationally, Dr. Gopa Iyer which is testing the idea that if we determine the mutation status of the patient's cancer cells, that if we have these critical mutations in these genes perhaps at the end of chemotherapy, if there's no cancer left and the imaging looks pristine, we might be able to safely observe them. And of course, patients always have the option of having the bladder out or have the option of having radiation. But in that trial, we are trying to test a very novel hypothesis of a chemotherapy plus re-scraping, re-TURBT after modality in a subset of patients. And we're using this molecular testing that we can do here at MSK to select those patients because we think that gives us that insurance policy that says this is a cancer that's likely to be wiped out by the chemotherapy by itself.

Dr. Bernard Bochner:  And we were all very excited about this particular strategy medical oncologists and surgeons, where we're trying to identify that subgroup of patient where they have a home run response to the drugs that you give them and I think that bladder preservation is something we all are striving to be able to expand out. The key I think for folks to remember is it's all about proper patient selection, identifying the right tumors that may work best, whether it's through sequencing or maybe there are just some clinical features, the size of the tumor, the number of tumors, and even a patient's specific history about recurrence patterns can come into play when we try to decide who may be best for a partial removal radiation and chemotherapy or one of these hopefully future approaches, which is genetic based bladder preservation. So, Jonathan, thank you. Let's bring in David, because David we've heard now some of the real exciting buzz words with respect to drugs now that are beginning to show some activity for bladder cancer. And these are being tested in patients who show up with more advanced disease. And so, let's talk a little bit about the patient who either shows up with disease outside the bladder or who's had definitive treatment and has then recurred in another part of the bladder. How do you determine what the optimal treatment is going to be for somebody with a more advanced problem?

Dr. David Aggen:  Thank you Bernie for having me join the panel today. As Dr. Rosenberg alluded to earlier at MSK, we develop an individualized treatment plan for patients that incorporates both clinical factors and patient factors. So, our team, I think it's important to note that our team doesn't take a one size fits all approach to this. We take into account patient's prior treatments, be it chemotherapy or immunotherapy. There are other medical conditions such as cardiac status and kidney status. And the available imaging and pathology data to try and develop the best treatment plan for each patient. In addition to offering standard chemotherapy and immunotherapy treatments, we have several clinical trials that are evaluating combination immunotherapies with the goal of improving outcomes for patients. I think all of our goal is just like the treatment plan with the highest chance of efficacy that minimizes side effects to patients. One of the ways we try and tailor treatment plans is to incorporate sequencing of patients cancers into the treatment paradigm. So, a standard pathology reporting includes histologic features of cancer. It tells us maybe the type of cancer by microscopic examination, but we've gotten more sophisticated over the last decade and we can perform more extensive molecular profiling of cancer. At MSK, we've pioneered the development of a comprehensive genomic profiling test called MSK Impact that can detect mutations associated with cancer and sometimes we find a mutation or we have a specific therapy to target that specific cancer.

Dr. Bernard Bochner:  David, can you just briefly kind of give folks a sense as to when you say mutations, what does that translate to? What exactly is that information providing you as a physician treating somebody with bladder cancer?

Dr. David Aggen:  It's a great question. So, we know that in bladder cancer, there are certain driver mutations. For instance, there's a mutation called FGFR3 that's specific to the cancer cells and for patients who have an FGFR3 mutation, there is an FDA approved treatment we can utilize. And having that additional information can help open up a new treatment option.

Dr. Bernard Bochner:  So, you're talking about matching up a specific treatment to a specific tumor kind of personalizing the approach for an individual patient?

Dr. David Aggen: Exactly and I think what makes us unique is that we have our own in-house assay to do this. Other cancer centers send to us or other places to do this type of testing. We're also using this data from MSK Impact to try and understand specific factors that might predict patient response. And in fact, MSK was awarded a specialized programs of research excellence grant or a spore grant from the NCI to try and better understand mutations that might predict response to immunotherapy. And I think at present, we have the only actively funded bladder cancer support grant in the United States.

Dr. Bernard Bochner:  Well, we're very excited about that. We know that that has incorporated leaders in the field like yourself, clinicians, the huge number of researchers that we have available at Memorial and the advanced technologies as well. So, David, is there an algorithm that people can kind of expect like for instance, is chemotherapy something that you're going to try first, if they're reasonable candidates or do you move to one of these more specialized approaches?

Dr. David Aggen: So, I think it depends on if patients have had prior exposure to chemotherapy. I think if they haven't seen chemotherapy before cisplatin or carboplatin-based chemotherapy is a standard treatment. We're looking increasingly at how we can incorporate immunotherapy either after or in combination potentially with these therapeutics. But at present, I think our standard is chemotherapy first.

Dr. Bernard Bochner:  And so, for the folks that may not have the response that we're hoping for, the complete response to chemotherapy, are there now immunotherapy drugs approved and available for people with advanced bladder cancer?

Dr. David Aggen: I'm so glad you asked because it's my favorite thing to talk about. So, there are in fact several FDA approved immunotherapies. I talk to patients when starting immunotherapy. I know starting any new treatment can be quite anxiety provoking, but in all honesty, most patients who are on immunotherapy feel pretty good in terms of day-to-day side effects. Chemotherapy is often given on a weekly basis, depending on the immunotherapy regimen, the treatments given through an infusion into the vein every two weeks or maybe every three weeks, depending on the exact treatment. One of the real advantages to working at MSK is we have a very skilled nursing team to administer these therapies. Many of my patients who are on immunotherapy can have this administered through a peripheral IV.

They don't require a Medi portal. And on the day of treatment, most patients don't experience any side effects from immunotherapy. It's very rare to see a side effect on the day of treatment. We are very cautious however to watch for immunotherapy side effects as patients are on treatment. The majority of immunotherapy side effects we can reverse with steroids, but we follow patients very closely because there are additional risks with immunotherapy. Another real advantage of getting treatment at MSK is we have access to doctors and other sub-specialties, including cardiology, neurology, dermatology, and nephrology if we identify these immunotherapy side effects and we can rely on their expertise to help try and mitigate any potential toxicity.

Dr. Bernard Bochner:  This has been a huge advance in the treatment of patients with advanced bladder cancer, because it's just up until a few years ago, we didn't have much to offer folks after they did not respond to chemotherapy. So, it's exciting, but as Dr. Rosenberg had mentioned it's not the panacea that we had hoped for. There's a subset that do fantastic with these, but what happens then if the immunotherapy is not as effective as hoped, what are the other future agents or even contemporary agents now that you might rely on?

Dr. David Aggen: So, we have other targeted therapies that are chemotherapy conjugated to antibodies and these therapies act sort of like smart bombs to bring the chemotherapy to the cancer. Dr. Rosenberg mentioned one of these therapies. It is Enfortumab Vedotin or EV. That's a standard treatment at MSK. We also have several clinical trials that are looking at combining EV with other treatments or combining immunotherapy with other treatments to try and rescue the response to immunotherapy and I think a real reason to be hooked into a center like MSK is to have access to these cutting-edge therapies.

Dr. Bernard Bochner:  It's utterly fascinating, the amount of progress that's being made at this point and I know having been involved in treating bladder cancer patients now, going on my third decade, I can tell you this probably is the most exciting time with respect to available options and what the research horizon is bringing us. And many of the drugs that you guys have been using in the advanced stage setting are now being moved towards earlier stages. Similarly, combined with surgery as Dr. Rosenberg had mentioned and we're excited to see that those advances as well. Well, we could probably spend two hours talking about these wonderful advances, but I want to bring in our wonderful Nurse Specialist, Vashti Livingston. So, Vashti for the patients that have undergone treatment, surgery, they've had a urinary reconstruction of some type, this includes reconstruction such as building new bladders for patients where they urinate through the normal pathway or we can build diversions through openings on the abdominal walls, stomas like the ilial conduit that requires an external appliance or an internal reservoir that they can catheterize through the abdominal wall. So, there's several available options for folks, but give us some sense about what the common concerns are that patients have about how normal their lives are going to be? You work with these folks daily.

Vashti Livingston:  Yeah, patients their first question is always, will I look normal? Will I be normal? Would anyone know that I've had some sort of surgery done, especially those who may have an external pouching system? Common questions are will I be able to exercise? Will I be able to go to the gym, play golf, tennis? Can I swim, travel? When will I be able to travel? What do I need to know for the TSC? What supplies should I have? For those who have an external diversion questions revolve around concealment of the pouch. Will my clothing change? What do I use during intimate moments? And a lot of the products that they use are interchangeable for concealment, exercise as well. Patients have questions about supplies. Ostomy supplies, is there insurance coverage, where am I going to get it? Who's going to help me, which is all part of what we do? If they've got an internal reservoir, I usually show them a sample of a catheter. Most patients may never have seen one and to discuss that there are different types that they can get samples, what their allotment is, insurance coverage and even with the neobladders. In the beginning, if a patient has to deal with using incontinence supplies, what are the different supplies? Is there coverage from insurance and how can we guide them as to what's appropriate at the appropriate time? So, we have all these discussions with our patients to help them with those concerns.

Dr. Bernard Bochner:  Well, I mean these are obviously questions that you get rapid fire on a regular basis and so Vashti, give folks a sense as to what the support resources are available? Clearly, patient's quality of life after surgery is a major concern to us. We want people to return to all of their preoperative activities or pre-treatment activities. And most of that can be achieved, but what kind of support can people expect?

Vashti Livingston:  Well, we've got bladder cancer support groups here that we offer. We've actually got two of them and right now everything is online. I'm a co-facilitator along with a social worker and the urology nurses, and we actually sometimes when patients are making decisions about diversions or even after surgery, before or after we advise them to use our support groups, because then they get to pick the brains of other patients who've gone through, share their experiences and the commonalities and the concerns, and to get the tips and the hints from someone who's actually lived through it. We also have a patient-to-patient volunteers who are specially trained several months to do a one-on-one and that's a very valuable resource for our patients in terms of that. As far as nursing goes, what is really unique to Sloan Kettering is that our patients get phenomenal postoperative care. They actually have outpatient clinics. We have regional WOCnurses, wound ostomy continence nurses. So, when I meet patients, one of the things people are concerned about, do I have to come back into Manhattan? I'm like, well, if you're in Long Island, are you closer to Commack or Uniondale? You could see Tracy out there or if you're in New Jersey, are you closer to Basking Ridge or [Indiscernible] [0:43:31]. You could see Lavinia or Christie out there or if you are in Westchester, you could go to Harrison and meet Krista. And I think this is really unique that we are there to see patients two weeks after surgery, two months, six months annually as needed for any concerns that may come up we provide that support and it's not just in clinic visits, but since COVID, we've incorporated telehealth into our communication and as a tool to help and educate our patients and support their family members.

Dr. Bernard Bochner:  So, patients can either Face Time or do some sort of tele-visit that you're able to help with as well. That's obviously very, very convenient for folks. As you mentioned the WOC nursing that may not be something a lot of folks are familiar with. Give folks a sense as to just how specialized your training and expertise is? What does that mean?

Vashti Livingston:  We are wound ostomy continence nurses and we have got months and hours, many clinical hours of working with patients with diversions and post-surgery wounds, incontinence management. What is crucial in our role and again, is unique to Sloan Kettering is our patients get a chance to meet a WOC Nurse preoperatively to do what we call the stoma site visit, which is part of the informed consent. Not only are we meeting the patient to place a specific mark in them for the surgeon, but it gives us an opportunity to assess their needs, their concerns, their understanding of the alteration to their bodies, what to expect, to show them samples, maybe identify specific needs like if someone has manual dexterity issues, if they're in a wheelchair, skin issues. And then when we do the actual markings, we go through a lot of maneuvers to make sure that it's in the right area of their body, away from the belt lines, where they can see things, whether they're putting in a catheter or whether they have a stoma and they have to put a pouch on if they've got scars, adhesions and we work closely with all the surgeons to make sure it's ideal for these people because research shows that the optimal placement minimizes the risk of leakage peri-stoma skin issues and of course, bothersome symptomology because the goal is to get people back independent and back on track with their lives.

Dr. Bernard Bochner:  And so, Vashti, when you mentioned stoma, what you're referring to here is in the subgroup of patients that have what we call an ileal conduit. This is the diversion type where there's no internal storage. We direct the urine flow out to a little opening on the abdominal wall. There's a little loop of intestine. That's used to divert the urine away. And because that drains continuously, the appliance that Vashti is referring to is what collects and stores the urine until the patient empties the urine bag itself. There are other forms of internal reconstructions as well. Many of our patients will be candidates for internal reconstructions of new bladders, which are also made out of part of the intestinal system and they can be hooked to the urethra. So, patients can void normally. These are very functional forms of reconstruction. They've been around now for about three decades. So, there's lots of experiences and are not new surgical techniques, but they are specialized techniques. And we know that experience does matter with respect to outcomes. So, Vashti, thank you so much that I think gives people a very good sense about what to expect and what kind of resources are available.

We'd like to thank all of the panelists for providing their expert input. We hope that these question and answers have helped allay some of your concerns and provided you with some information that'll be helpful through your journey. And we want to thank the public relations group and the center for providing the opportunity for this special information session. We look forward to seeing all of you again hopefully at another upcoming session. Until then thank you for all of your attention.