Bladder Cancer Care: Expert Insights for Informed Treatment Decisions

Katherine Banwell:

Hello, and welcome. I’m Katherine Banwell. Today’s webinar is part of PEN’s Elevate series, which aims to help patients and care partners feel confident and well-informed when making bladder cancer care decisions with their healthcare team. Today, we’ll hear directly from an expert.

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest, Dr. Piyush Agarwal. Welcome. Would you please introduce yourself?

Piyush Agarwal:

Yes. Hi. My name is Piyush Agarwal. I’m a urologic oncologist. I focus in bladder cancer, and I’m the vice chief of urology and the head of the bladder cancer program and the director of the urologic oncology fellowship at the University of Chicago Comprehensive Cancer Center. And I’ve been doing bladder cancer and managing the disease, patients, research, ever since I finished my fellowship back in – oh, boy – 2008, so it’s been a while doing this. I really enjoy it. And really, thank you for the opportunity to participate in this webinar today.

Katherine Banwell:

Well, thank you for joining us. We’re really glad to have you with us. And you mentioned a little bit of your background and what you’ve been doing. Your work as a researcher in particular I’d like to know a little bit more about, because you’re on the front lines of advancement in cancer care. What led you to focus on bladder cancer? And why is this work important to you?

Piyush Agarwal:

Yeah, I think a lot of times we’re a product of our experiences and what we were exposed to early. And in my training, I just found that bladder cancer, back when I was a resident from pre-2000, there was very little innovation in bladder cancer, and it was a quite morbid surgery. And they were the worst outcomes compared to other urologic cancers. I remember my chairman at the time basically told me, “If you want to make an impact in urologic cancers, bladder cancer is a place that needs more innovation, better treatment options.”

And so, that was 20-plus years ago. And he also said it’s a great opportunity for a young investigator to try to achieve something in their career. Based on his advice, and kind of the state of bladder cancer, and my exposure – and then I did a fellowship with MD Anderson, which arguably is one of the better places in the country for bladder cancer care – that sort of led me down this path.

Katherine Banwell:

Thank you for that. When it comes to choosing therapy for bladder cancer, it’s essential for a patient to work with their healthcare team to determine what’s best for them. How would you define shared decision-making, and why is it so important for managing bladder cancer care?

Piyush Agarwal:

Yeah, so the issue is, there are some states of the disease where there are different options for therapy. And that is a point where ultimately the patient has to bear the burden of the disease based on the treatment chosen. Certainly we try to stress the positives of the treatment and the expected outcomes, but we also try to highlight the potential side effects. And so, it’s very important that we as providers have a really comprehensive discussion with patients of the different treatment choices available, the possible outcomes of those treatment choices, both from efficacy and from side effects.

And that’s where it’s really important to work with our patients and to really inform them, so they can make a good decision for themselves. And that’s where there are some great resources out there on the web, or there are printed materials that we can use to sort of help educate patients. Ultimately, a lot of the education comes at the consultations we have with the patients in the office prior to treatment.

Katherine Banwell:

It’s the patient and care partner and doctor and the healthcare team all working together.

Piyush Agarwal:

Yes, yes. And I think it’s not just a one-time sort of interaction. And I always try to tell my patients, “Look, take some time to review this material. Don’t need to make a decision today. Why don’t we come back and revisit this in a week? And at that point, you’ve got some more knowledge, and you might have some more questions for me after you’ve had a chance to look at this material.” We try to come up with a decision over a few interactions as opposed to one office visit.

Katherine Banwell:

What are the treatment goals for bladder cancer?

Piyush Agarwal:

I think quality of life is probably first and foremost. That can take the form of if you are trying to preserve your bladder, are we able to leave you with a bladder that’s worth preserving? I think if you asked every patient, “Would you like to preserve your native bladder?” almost everybody would say yes; but the other issue becomes at what cost and if your quality of life is significantly impacted by repeated treatments, urinary frequency, urgency, inability to hold your urine, then sometimes the treatment choice may need to be more aggressive in order to achieve a better quality of life.

I think that is, obviously, if bladder preservation can be done while maximizing quality of life, then that would be sort of another main treatment goal for patients. And then I think if bladder preservation cannot be done, then I think trying to provide patients with an option that they can live with and still enjoy doing the things that they are doing prior to their cancer diagnosis. I think this is where, again, the discussion is important as to what are the patient’s goals. I’ve had some patients who want to rid themselves of the cancer, so they choose the most aggressive treatment, and that might mean not preserving their bladder.

And I’ve had patients who will do anything to preserve their bladder and will accept really poor urinary function, just because they want to save their native bladder. Every patient’s different. We try to work with them to maximize and prioritize the goals that are important to them.

Katherine Banwell:

Thank you for giving us this information about treatment goals. I’m wondering if you could now provide an overview of the typical testing that follows a bladder cancer diagnosis.

Piyush Agarwal:

Yeah, so usually this diagnosis comes to light after a patient has blood in the urine, and then eventually patients are referred to us. And there’s an issue with delay in referrals and delay in diagnosis.

Tends to happen more in women, unfortunately, because often blood in the urine is often interpreted as a urinary tract infection and may prompt repeated treatments. Eventually when a patient is referred to us for blood in the urine, we will look inside the bladder visually, with a procedure called cystoscopy, confirm that there is, in fact, a tumor or suspicion for tumor.

We will obtain a urine cytology that will give us a glimpse of whether there’s any high-grade bladder cancer cells. And we’ll get some sort of imaging to make sure there’s no evidence of disease in the upper urinary tract or outside of the bladder or the upper urinary tract.

And so, after that information, if we find something suspicious, we’ll take the patient to the operating room and sample, and potentially remove, all the tumor that we can through an endoscopic minimally invasive procedure using their urethra as a natural opening in the body to get into the bladder and to sample and remove the tumor entirely, if possible. And at that point, we then have our information, which is what is the grade of the tumor and what is the stage of the tumor.

And if it’s a low-grade, low-stage tumor, then those patients often can be treated with local therapies in the bladder and have periodic surveillance with cystoscopy, with agents in their bladder periodically. High-grade tumors that are low-stage, so that they’re not in the deeper layers of the bladder, we potentially could also treat with that option, although the treatments in the bladder may be more intensive and more frequent; but again, in an effort to preserve the bladder. The grade and the stage are very important to sort of determine how best to treat our patients.

Katherine Banwell:

Well, thank you for explaining that, Dr. Agarwal. What questions should patients be asking about their test results?

Piyush Agarwal:

I think patients should ask, “What is my grade and stage? What is the risk of recurrence? What is my risk of progression? Are there any other tests that we could potentially do? Is there anything I can do as a patient to lower my risk?”

And I think asking some of these questions will allow the patients to be a little bit more potentially involved in their care, and also try to understand a little bit more about the disease process. I encourage my patients to really ask as many questions as they can, but really grade, stage, prognosis, recurrence, progression, and anything else they can do to lower the risk, I think are all really good basic questions to ask.

Katherine Banwell:

You’ve touched upon various treatments available. What options are currently available for people diagnosed with bladder cancer?

Piyush Agarwal:

There are kind of different states of bladder cancer, so if I refer to localized bladder cancer – so cancer that’s just in the bladder and not deep within the wall of the bladder – we have a standard drug called BCG, and we have another set of drugs, a type of chemotherapy regimen, that many of us use that is a doublet of gemcitabine (Gemzar) and docetaxel (Taxotere).

And then if patients don’t respond to that, and they have high-grade BCG, unresponsive tumor, there are some novel agents that have been approved in the past couple of years for use in those patients. There’s a product called nadofaragene firadenovec-vncg (Adstiladrin). Another one used to be called N803.

The trade name is Anktiva, and that is combined with BCG. And then there’s another, newer product called gemcitabine intravesical system (Inlexzo) that used to be called TAR200 that was also recently approved. These three agents are available now for patients.

And then if you think about muscle invasive, or a locally advanced, or maybe an early metastatic bladder cancer, there’s a novel combination which has really shown some – really has changed the paradigm for how we manage locally advanced disease there. It’s a combination of two drugs.

One is called enfortumab vedotin-ejfv, known by the trade name Padcev, and then combined with an immunotherapy called pembrolizumab, known by the trade name of Keytruda.

And this combination has been really amazing. In fact, it’s been shown to be superior to standard chemotherapy with gemcitabine (Gemzar) and cisplatinum for locally advanced and metastatic bladder cancer. This has really changed the way we manage these patients. And so, it’s an exciting time in bladder cancer for us as investigators, because we now have more tools to offer our patients and potentially can achieve better outcomes.

Katherine Banwell:

Dr. Agarwal, how do clinical trials fit into a bladder cancer care plan?

Piyush Agarwal:

There’s certainly a large amount of clinical trials going on in the bladder cancer space. And thankfully, those have led to the recent EV-pembro combination that I referred to.

That was discovered to be the superior regimen after the culmination of a bunch of clinical trials. And recently, the most recent one was presented at the GU ASCO meeting recently in San Francisco. I would say a lot of the advancements we’ve seen are the direct results of clinical trials. Those three novel agents that I mentioned that were approved for BCG unresponsive disease also were the results of clinical trials.

And at any given moment, there’s a large amount of clinical trials. There’s still ongoing clinical trials in the BCG unresponsive state for bladder cancer. There’s also clinical trials for those patients who have been exposed to BCG, but comparing another round of BCG versus a novel agent. There’s clinical trials for even BCG-naive patients, trying to treat them with a novel regimen that may or may not be done in conjunction with BCG.

There are some great resources on clinicaltrials.gov, and other organizations also have websites devoted to clinical trials. And that’s one thing I should have mentioned earlier when you had asked, “What can patients do?” Patients can go to these clinical trial websites and then ask their provider, “Hey, am I eligible for this clinical trial?”

Katherine Banwell:

I wanted to talk about factors in treatment. You did touch upon them, but could you walk us through the key factors considered when deciding on a bladder cancer therapy?

Piyush Agarwal:

Yeah, so we will typically place patients based on their pathologic features into a low-risk category, an intermediate-risk category, or a high-risk category. And fortunately, in bladder cancer, a lot of us have come up with treatment algorithms for these different risk groups. For low risk, usually using a one-time chemotherapy treatment at the time of a tumor resection with surveillance. It works very well in most patients.

Those patients who are intermediate risk, which are typically low-grade tumors, but that either recur frequently or are very large, those patients in the intermediate-risk category, which could also include some high-grade tumors that are very tiny, there are some new novel agents that were recently approved that can be used in lieu of actually resecting and surgically operating on patients. What we’ve been doing for a while, which still continues to work, is we can also resect the tumor surgically and give them sort of adjuvant bladder installation.

That’s an area that a lot of companies are doing clinical trials in, to see if they can offer a product that’s more effective than what we have currently. That’s an active area of trial investigation. And then for the high-risk patients, then that will guide treatments like BCG and those other novel agents. Yeah, the grade is very important, and the stage, because then that determines the risk group, and then the risk group really determines very algorithmic treatments.

And so, that’s what I like about bladder cancer opposed to other urologic cancers we treat, that it is sort of – we as a community have done, I think, a good job at sort of specifying how these tumors should be treated. And I feel that most patients can get really good care with most providers, because we’re all sort of adhering to these treatment algorithms.

Katherine Banwell:

Can you define the risk groups? Low, intermediate, and high?

Piyush Agarwal:

Yeah, so low-risk tumors are low-grade tumors. Essentially, low-grade tumors, less than 3 centimeters. Solitary low-grade tumors, these are tumors that fall into the low-risk category, those that take more than a year to recur, so a low recurrence risk, small size, and solitary tumors. The intermediate risk category is mostly made up of low-grade tumors, but low-grade tumors that are larger, so 3 centimeters or greater; low-grade tumors that are multifocal, or low-grade tumors that recur more often than beyond a year. You’ll have some of these patients who have tumors every three to six months.

When you look in their bladder, they recur and then they’ve got to go back to the OR, or they want some sort of intervention done. That’s the intermediate risk category. Now, some of us will also add high-grade tumors that are very small, less than 3 centimeters, and solitary to that group. There are others of us that feel that all high grade tumors should be in the high-risk category. That’s a little bit of an asterisk, whether or not that that select high-grade tumor should be incorporated in the intermediate risk group.

Everyone agrees that high risk includes any high-grade tumor greater than 3 centimeters, any high-grade tumor that’s multifocal; any CIS, which is the flat tumor. Any tumor that is in the Lamina propria, which is stage T1, is also considered high grade. Because of the risk group definitions, it gives us a good way to treat our patients, because based on the risk, we have treatments that they’re eligible for.

Katherine Banwell: 

Symptoms of bladder cancer and side effects of treatment can vary widely. How do you approach symptom management with your patients?

Piyush Agarwal: 

I tell them up front what you can expect are things such as frequency, urgency of urination, occasionally incontinence because of the urgency; waking up at night, more nocturia, and sometimes some burning with urination. And so, these are situations where I tell the patients, “Be aware of the symptoms.” A lot of times these symptoms are short-lived after a treatment or a surgery. If these treatments continue to – if these symptoms continue to persist, we’ll often use a variety of drugs, and these could be anticholinergics, to try to expand the bladder and decrease the urgency.

They can be anesthetics for the urinary tract, that try to numb the urethra so that there’s less burning with urination. Sometimes it could be medications that help particularly in a man. They can basically relax the prostate to make it easier to urinate. There are some drugs we can use to make the symptoms a little bit better. There are some other drugs we can use that are sort of last resort medications.

For the most part, if patients are kind of counseled, you can expect your urinary symptoms to get potentially worse after an intervention, but reassure them that they should get better slowly over time. Then they’re less concerned about it. There are some medications we can use, albeit limited efficacy. And there are some patients that have just such profound symptoms that we can’t treat them further, and we have to think of other ways to treat them. For the most part, we can treat most patients and get them through these therapies.

Katherine Banwell: 

Why is it so important for patients to report side effects or new symptoms to their care team? And why is early intervention critical?

Piyush Agarwal: 

If patients inform us about their symptoms with standard of care medications, it is the earlier we know about a symptom, the earlier we can prescribe a treatment or we could modify a dose of our intervention so that we can make it more tolerable to patients.

There’s good data, with modifications in dose, with reducing the frequency, with potentially adding an antibiotic, we can potentially make treatments more tolerable. We can’t really do those things if the patients don’t report it, so it’s very important that patients communicate with their providers about their symptoms.

Katherine Banwell: 

Managing a bladder cancer diagnosis can bring emotional challenges like anxiety and fear of recurrence. Why is it important for patients to share emotional concerns with their healthcare team?

Piyush Agarwal: 

I think that a big part of managing one’s cancer is also to manage one’s mind and emotions. Personally, I feel that if you can’t manage those other symptoms, unfortunately, your outcome may not be as good. I do believe in this thought of the mind having an important role in healing the body. I just think emotionally, we need to provide support for our patients to get through this really rough time. I often will tell patients, “Look, it’s normal to have what we describe as an adjustment reaction to bad news.”

It’s normal to feel angry and agitated and anxious, but if that’s debilitating and the patient is having difficulty coping with that, then I often recommend discussing with their primary care provider potentially the use of a low dose antidepressant for a short period of time. And I think there should be no shame in considering something like that. I think of that just as another way, an adjunct to proper treatment for the cancer. There are some patients who have the ability to cope with this type of news and have a very supportive family, but there are other patients that may not have those assets, and so they need some help.

I do think that there is a role for that, and we as providers should discuss that and bring that up with our patients so that they’re aware that those are available to them should they need them. I also like to set expectations for them, and I think that can be helpful. I tell them, “Look, for low-risk tumors, I tell patients it’s really unlikely there’s going to be progression. And as long as you keep up with appointments, we can usually manage your bladder. We may have to do some procedures along the way, but usually as long as your bladder is functioning, you can maintain your bladder.”

Whereas for my high-risk patients, I tell them, “Look, we’re going to do our best to preserve your bladder, but you have to understand that if none of these therapies work, then potentially bladder removal or radiation are things down the road.” And I think if I set expectations for people, it’s a little bit less traumatic if their tumor is not responding to the treatments that we’re using, and we start escalating therapy. I think if they know that that’s a possibility, it’s a little bit easier for them to comprehend and adjust to it in the future.

Katherine Banwell: 

Financial concerns are also common. Where can patients find financial assistance and resources?

Piyush Agarwal: 

Yeah, so, unfortunately, there is this term of financial toxicity, and it’s a real entity, especially for patients under 65 who are self-employed and may not have insurance. Fortunately, a lot of medical centers will work with patients on providing reduced cost for evaluations. A lot of the manufacturers of some of these agents can offer their medications at a significant discount and in some cases just for a small co-pay. If patients – obviously we ask them to, if they have government benefits that they can potentially leverage, that is also an option.

Fortunately for bladder cancer, the average age is around 65, 66. Most of these patients have some sort of Medicare plan, and that usually will provide most of these standard treatments for bladder cancer. I find we really have to work with our underinsured patients under the age of 65. Those are patients that it’s challenging sometimes to provide appropriate care and limit the cost of that care, especially for those who kind of have their own small business and they really don’t have the insurance. There are things we can do to give them time to get insurance.

And there are procedures we can do and sort of one-time treatments we can do that will sort of treat their bladder and buy them some time to get the insurance they need. Unfortunately, I think this is a problem that affects all of healthcare in the U.S., is that we don’t have, unfortunately, universal insurance for those under 65. And it can be challenging for those patients in whom they don’t have insurance through employers.

Katherine Banwell: 

Thank you for that, Dr. Agarwal. As we close out today’s program, I wanted to know what gives you hope about the future of bladder cancer care.

Piyush Agarwal: 

What gives me hope is when I go to a medical conference, and I see some amazing data that is allowing patients to preserve their bladder and have a resolution of their metastatic lesions and get meaningful survival that’s not months but years. And when you see an audience get up and actually clap for the data that was presented, it’s very heartwarming.

I feel really privileged to be in a community of providers that is making rapid advances in really what was a terrible disease 20-plus years ago, when I started my training; and to see the advancements that have been made to the point where people are visibly clapping at a meeting and giving standing ovations for data that is being presented. It gives me hope that we will eventually get to a point where we’re not going to have to remove patients’ bladders. And we’ll eventually get to a point where patients are going to get meaningful survival.

And this becomes a chronic disease that they live with and not a morbid disease that they die early from. I’m encouraged that there’s a future that will have that. And I’ve seen so much progress already that it really gives me hope that there’s even a brighter future ahead of us.

Katherine Banwell: 

Dr. Agarwal, thank you so much for taking the time to join us today. It’s been a pleasure talking to you.

Piyush Agarwal: 

My pleasure. Thank you so much for having me.

Katherine Banwell: 

To learn more about bladder cancer and to access tools to help you become a proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell. Thanks for being with us.