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Transcript of What to Know About BCG Treatments for Bladder Cancer with Dr. Ashish Kamat

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Voice over:

This is Bladder Cancer Matters, the podcast for bladder cancer patients, caregivers, advocates and medical and research professionals. It’s brought to you by the Bladder Cancer Advocacy Network, otherwise known as BCAN. BCAN works to increase public awareness about bladder cancer, advances bladder cancer research, and provides educational and support services for bladder cancer patients and their loved ones. To learn more, please visit bcan.org.

Rick Bangs:

Hi, I’m Rick Bangs, the host of Bladder Cancer Matters, a podcast for, by, and about the bladder cancer community. I am also a survivor of muscle invasive bladder cancer, the proud owner of a 2006 model year neobladder and a patient advocate supporting cancer research at the Bladder Cancer Advocacy Network, or, as many call it, BCAN, producers of this podcast. This podcast is sponsored by Seagen/Astellas alliance and Genentech. I am pleased to welcome today’s guest, Dr. Ashish Kamat, who is back for his third podcast. Dr. Kamat is a professor of urology and director of bladder cancer research at MD Anderson Cancer Center in Houston, Texas. He’s also a member of the Bladder Cancer Advocacy Networks Scientific Advisory Board and leads two organizations that are focused on bladder cancer, the International Bladder Cancer Group, IBCG, and the International Bladder Cancer Network, IBCN. Dr. Kamat, welcome back. I’m so excited to have you join me on our podcast again.

Dr. Ashish Kamat:

It’s always a pleasure to be here with you, Rick.

Rick Bangs:

Let’s start with a BCG refresher. What is BCG and why, after so many years, is it still the gold standard in most cases for non-muscle invasive bladder cancer?

Dr. Ashish Kamat:

Let’s start with that second half first. Why is it the gold standard? Well, when you think of a gold standard, you essentially are looking for something that is the best. When it comes to BCG, it is the best immunotherapy we have for cancer period, not just for bladder cancer, but across all cancers. There is no immunotherapy despite all the hoopla that you see in the news and the media today, even with the newer agents that has a higher efficacy rate than BCG for non-muscle invasive bladder cancer.

That’s why it’s the gold standard or the platinum standard or titanium or whatever metal you want to use. Now, what is BCG? I sort of hinted a little bit. It is an immunotherapy. It is an attenuated tuberculosis bacteria that was developed first as a vaccine against tuberculosis. But while studying its properties as a vaccine, the original investigators found that it has potent immune stimulatory effects. In fact, it was first used to treat melanomas, leukemias and other cancers. But when it came to bladder cancer, it was sort of morphed into a bladder cancer treatment by two pioneers, Dr. Morales and Dr. Lamb who discovered its property and then utilized it to treat bladder cancer. In summary, it’s an immune therapy derived from an old tuberculosis vaccine that is used to treat bladder cancer.

Rick Bangs:

We know some things about BCG, but what don’t we know about how it works? How familiar are we with the mechanism of BCG and how it works?

Dr. Ashish Kamat:

The mechanism of BCG is very complex. Because it’s so complex, you’ll often hear people say that we don’t understand how it works, which in some ways is true. But it’s not a negative. It’s not that we don’t understand how it works and that’s why it’s not good. It’s just that there are so many different complex immune pathways that are activated by this one agent that we still to date, haven’t fully understood all the nuances of what happens.

The technology has improved over the years to allow us to study it better. We know now that BCG not only stimulates the innate immune system, but also recruits different T cells and natural killer cells that are somewhat sometimes laying dormant and allow them to fight the patient’s tumor, in this case bladder cancer. What’s also interesting in recent years, and especially during the pandemic with all the work that went on trying to use BCG as a vaccine against COVID, is that people recognize that it also harnesses and activates the memory of the immune system to pathogens other than the targets. In other words, if you use BCG to simulate the patient’s immune system, it also acts in some ways as a modifier of the innate immune system to other pathogens such as COVID 19 or yellow fever, influenza, et cetera, et cetera.

Rick Bangs:

Wow. What can patients expect before a BCG treatment? Is there any sort of preparation that they can do in advance of arriving at the clinic?

Dr. Ashish Kamat:

Let’s assume, of course, for the purpose of this discussion that the patient and his or her urologist has had the appropriate discussion that BCG is appropriate for them because that’s one of the key things. It’s not for everybody. It is a very potent drug and there’s a worldwide shortage right now. We want to make sure that it’s not used, for example, low risk patients. But assuming it is appropriate for the particular patient, usually the treating physician, the clinic will give patients a sort of advisory sheet, which tells the patients a few things. Number one, restrict their fluid intake the morning of the day that you’re going to have the installation. The reason for that is not because dehydration helps BCG work better or because we’re trying to make our patients feel dry of mouth, but it’s because the patient has to hold the treatment in the bladder for 60 to 90 minutes, ideally, even two hours if possible.

Of course, if you have a lot of fluid intake and you’re making urine in addition to holding the BCG, it’s hard for a lot of our patients to have a two-hour bladder capacity without wanting to go to the bathroom. Because of that, we’ll often tell patients to restrict their caffeine intake, if they drink a lot of coffee or tea that makes them go to the bathroom. We’ll have them restrict diuretics, if it’s medically safe for them to do so. Those are sort of the fluid restrictions. The other thing we often advise patients to do is at least the first time they’re having BCG instilled, bring someone with you to the clinic, because you never know what sort of allergic reaction you may have, or you may have an enhanced immune response and you may need to have someone drive you home. But after the first installation, once patients are used to it, we often have patients that come in, drive in, get the treatment, and then go to work or go home and drive themselves.

That’s not an issue. The other thing that is important for people to know is that the BCG is a live attenuated bacteria, but it is still a bacterium. If a patient is taking antibiotics and sometimes the primary care physician may give the patient an antibiotic for a sinus infection or something else, it can sometimes kill the BCG before it has a chance to work. Always make sure that you tell your urologist of any other drugs you’re on, especially, if they’re antibiotics. Oftentimes, you may have to skip the dose of antibiotic for the first 24 to 48 hours of your BCG installation.

Rick Bangs:

Okay, good advice. Now, I’ve shown up at the clinic and what’s going to be done to get me ready and is that going to be the same if I’m a man or a woman?

Dr. Ashish Kamat:

Essentially, yes. The process is the same if it’s a man or a woman. Of course, you go to the room, hopefully, you’ve had the discussion with the urologist and you know what side effects you might expect. The first thing that the nurse or nurse practitioner will do that’s instilling the medication is have you empty your bladder. Now, oftentimes, our patients that bladder cancer are not able to completely empty their bladder, but the more you can empty it yourself, the smoother the process goes. After that, a catheter will be instilled into the bladder. With that catheter, any residual urine is drained, again, to facilitate your ability to hold the BCG and the bladder for the appropriate amount of time. Once the residual urine is drained, the medication is instilled into the bladder. It comes in a pre-made formulation with the fluid and the BCG already in a mixture.

Once the catheter is used for the medication instill, the catheter is taken out. Now, it’s important that the catheter’s taken out because that actually allows the patient to hold the BCG in the bladder longer than when the catheter is left in for two reasons. Number one, the balloon at the end of the catheter occupies space. But number two, just having a catheter in the urethra, especially past the prostatic urethra in men acts as an urgent and the bladder can go into spontaneous spasms. Now, if you as a patient have a history of having an overactive bladder and need some pre-medication, you may be given a prescription for an antispasmodic to take the morning off your arrival. If you forget, please let the clinic folks know, so they can actually give you an antispasmodic. The last thing we want to do is have you have the medication instilled and then spontaneously void it out before it has had it chance to do its work.

Rick Bangs:

When I had a cystectomy, I think, there’s lidocaine that’s put in. For BCG, that isn’t the case?

Dr. Ashish Kamat:

No, in fact, we do not want to use lidocaine for BCG installations. The acidic pH of the lidocaine can actually kill and clump the BCG bacteria. Oftentimes, you’ll hear of patients that have lidocaine instilled because of course the nurse is trying to be kind to the patient. When that is done, it actually can decrease the efficacy of the BCG. Lubrication is fine and that’s normal. Again, you don’t want to use too much lubrication, because the lubrication can clump the BCG. The K-Y jelly can clump the BCG and it may not distribute within the bladder itself. But you don’t want to use lidocaine. Unless, of course, you absolutely have no choice and someone is so sensitive to the catheter that they just can’t do it without lidocaine, which is really rare by the way. In that case, you have to take the compromise or decrease efficacy. But ideally lubrication, yes, not too much lubrication. Lidocaine, no.

Rick Bangs:

Okay. I know because I hear patients talk about this and they tend to be quite nervous before the treatment, particularly the first treatment. Is there anything that can be done to mitigate my nerves before I have my treatment?

Dr. Ashish Kamat:

I think the best thing to do is have a frank discussion with the treating physician and their staff as to what to expect. The other thing is really don’t expect to be in pain. There’s this thought process that I’m going to have a catheter put in my bladder, which many patients are used to because they’ve had a cystoscopy. But it’s the medication going in the bladder and because it’s an immune therapy, what’s going to happen? Am I going to have spasms et cetera, et cetera? If you are nervous about spasms or you think you’re going to have spasms because of your prior experience with your own bladder, like I said, talk to your physician and get the antispasmodic prescribed.

Very, very rarely patients are anxious enough that they actually require a pre-medication with an anxiolytic. Obviously, they can’t drive home at that point. But it’s very rare. I mean, with appropriate counseling and I take the time to, of course, counsel my patients and talk to them. It’s very uncommon for a patient to truly, actually be nervous or nervous enough that it’s beyond the range of what you’d expect to be nervous when you just show up at a doctor’s office.

Rick Bangs:

Okay, speaking of nerves, I know there’s some relationship between nerves and relaxing the pelvic floor where that catheter is going to go in. Is it like self-catheterization in that I get best results and least discomfort if I just relax and don’t clamp down?

Dr. Ashish Kamat:

Absolutely. You hit the nail on the head. Oftentimes, you’ll hear stories of patients that will tell you that, “Oh, I was talking to the nurse or doctor and we were cracking a joke and before I knew it, the catheter was in.” The reason we do that and distract patients during cystoscopies or catheterizations is not because we’re truly trying to crack a joke. But we are trying to distract the patient, so they’re not tensing down and not clamping when the catheter’s passing through that sphincter. That’s usually the first couple of times.

After that, patients really get the sense of how to relax. Some patients like to wiggle their toes. Some people focus on the distant point. Some try to think that they’re urinating. Different things work for different people. But the bottom line is, yes, you hit the nail on the head, you want to relax the sphincter as the catheter is going through, so it doesn’t hurt. It’s almost like if I tell you don’t think of an elephant, you will think of an elephant. If I tell you specifically, don’t clamp down, you will clamp down. It’s something that the patient has to learn to do.

Rick Bangs:

Right, right. Okay. Now, I’ve been prepped and I’m getting my treatment. What are the mechanics of that?

Dr. Ashish Kamat:

Fairly straightforward, like I said, you’ll have a little bit of the lubrication instilled into the urethra. A catheter will be placed. Once the catheter is placed, the urine is empty. The medication is put in the bladder. The catheter comes out. The first time, we actually have the patients wait in the office for the full two hours before they leave mainly, because we want to make sure there’s no unusual allergic or other reaction. Once the patient’s used to doing the treatments, he or she’s free to leave the office once the medication’s put in. We’ll talk, I’m sure a little bit about the precautions once you get home or to your bathroom, et cetera. But they get those instructions and they don’t have to be in the clinic to empty the bladder. They can actually empty the bladder once they’re home.

Rick Bangs:

Okay. Is there pain involved before, during and after the treatment? How does that pain get managed if there is any? Are men more apt to have pain than women or women than men?

Dr. Ashish Kamat:

The discomfort from the catheter insertion is the only part that’s actually truly uncomfortable when it comes to pain per se. Yes, men have a harder time with that because of the prostate and the sphincter. That really is not something that is for the most part needs to be medicated because like I said, it’s the time of insertion. Of course, we can sometimes give you anxiolytics, if needed. But once the medication’s put in and/or when you’re avoiding it out, patients may feel a sense of burning and a sense of warmth almost like they’re having a urinary tract infection. I often, during the counseling, tell my patients that if you’re having what seems like urinary tract infection, that’s good. It makes me happy, because it means that your immune system’s getting ramped up. You should not be startled or feel that that’s causing a problem.

Some patients have an even more heightened immune response. They may have a low-grade fever. Fever that lasts four hours or even sometimes eight hours. All that is good. It’s not painful. It is uncomfortable. It’s like how some people react to getting the flu shot or the COVID vaccine. They have an immune response that’s surmounted. Taking things such as Tylenol, a little bit of Motrin, all of those supportive cares that all of us now are used to hearing when it comes to vaccinations is completely appropriate. When the patient voids the BCG, there might be some burning. Again, a medication is coming out, you’re avoiding it out, there might be some burning when you urinate. But that’s self limited. After the patient voids, he or she can drink plenty of water to keep things flushed out and that helps.

Rick Bangs:

Okay, if the BCG has been installed, I think you said 60 to 90 minutes, I’d have to hold it. Whether that’s true or not, do men and women have equal difficulty in holding BCG before urinating?

Dr. Ashish Kamat:

Sixty minutes is the bare minimum. Ideally, 90 minutes to 120 minutes. It allows the bacteria to adhere to the bladder epithelium. Now, keep in mind, these are live attenuated bacteria, so the longer they stay in the bacteria, they stick to the wall. Once the patient empties the bladder, it’s not like all the bacteria are coming out because some of them are still stuck to the walls. That’s good. You don’t need to hold it for three to four hours, and if you could because that really doesn’t add that much to its efficacy. No, to answer your question, in general, there’s not any difference between men and women specifically to the question you asked about holding the medication in the bladder. Unless, they have a preexisting condition from their prostate, enlargement, et cetera.

Rick Bangs:

Do I have to rotate when I have it installed? Because I hear some patients talking about rotating or not rotating?

Dr. Ashish Kamat:

That’s a classic myth that’s propagated from generations to generations down the road. The rotisserie, where the patient has BCG put in the bladder and there are 15 minutes on one side, 15 minutes on the other side, et cetera. It’s a myth. The thought process behind that was that if by chance while instilling the medication in the bladder, some air got in through the catheter, et cetera, then having the patient rotate will allow the air bubble to move around from side to side.

The bottom line is air doesn’t get in. Even if it’s one or two bubbles like we see during cystoscopy, those are tiny enough and the bladder is a hollow organ that gets compressed. That actually having the patient get up and walk around jostles the BCG more than enough to get it to adhere everywhere. But it’s important that the patient is active. If a patient has the medication instilled and lays completely still, then yes, some of the air bubbles, again, small. But they may prevent adhering of the BCG to the dome of the bladder. That’s why, like I said, we have the patient get off the bed, walk around, just do normal activity, but you don’t have to go around and around forever.

Rick Bangs:

Okay. All right. Then so now, I’ve voided out the BCG, at what point will you let me go home?

Dr. Ashish Kamat:

Like I said, you could go home before you void out the BCG. Once we know that you are tolerating the BCG well. Wherever you are, whether you’re at home or you’re in the clinic, there’s some precautions you need to take. Now, full disclosure, the label insert and the instructions from the company state that you have to be in a bathroom that’s only yours. Nobody else goes in there. You have to take bleach. You have to wipe down the toilet. You have to pour bleach down the toilet, et cetera, et cetera, et cetera. Let me back up a little bit and just mention to our patients that are listening or anybody that’s listening. BCG is used across the world and given to newborn infants as a vaccine. It’s given to infants of mothers who have active HIV and are born. It’s given to old people to help boost their immune system other than for bladder cancer.

It is very safe. The reason for all that in the literature is legalese. Yes, in theory, your doctor will tell you to do that. But in practical terms, keep your bathroom clean. If you spill urine outside the toilet, wipe it down. If you want to wipe the seat of your toilet, if the seat has been down, then wipe it off with a wipe, that’s fine. But the bottom line is if you keep your toilet clean, you don’t splash it everywhere and you make sure that nobody that’s immunocompromised. If you have a patient at home or a family member that’s had a stem cell transplant, for example, or is totally immunocompromised, clearly that person shouldn’t be around any biologic. But if a person is normal and healthy, just being in the vicinity of somebody who’s gone to the bathroom and voided BCG will not cause a problem.

Rick Bangs:

All right. Now, I’m home or I’m back at work, whichever and what can I expect in terms of side effects?

Dr. Ashish Kamat:

A little bit of a urinary tract infection type sensation. A little bit of burning in the bladder. A little sensation of warmth. Maybe a low-grade fever, usually self-limited, anywhere from four, maybe six to eight hours. If it gets to be more than a low-grade fever and it lasts long, make sure your doctor knows right away. Because that could be an early sign that you’re actually getting an infection from the BCG, which again is good from an immune standpoint, but if left unchecked can cause your side effects.

Rick Bangs:

Okay. Now, would these side effects vary across treatment? Would they increase as I had more exposure to BCG? Would they vary between that first time I had the BCG, which is called the induction phase or the maintenance phase? What’s the continuity?

Dr. Ashish Kamat:

The side effects that are related to the BCG itself definitely get enhanced with increased exposure. It makes sense because with increased exposure, the immune system getting ramped up where recruiting more of the appropriate cells and it’s the T cells, the NK cells, all of those that actually cause the side effects as well. Absolutely. I always tell patients that after the induction course or towards the end of the induction course, you might start to notice increasing side effects that we just mentioned. Once a patient has the induction and they come back for the maintenance course, over time the bladder gets sensitized and the patient may get increased side effects. It’s important for the patient to let us know, and again, I tell them all the time, let me know if the side effects are increasing because even though that’s a good thing, I don’t want you miserable enough from the side effects that you can’t complete the full three-year course of BCG, if that’s what was prescribed to you.

Because the data suggests that the duration of treatment is much more important than the dose of treatment, which brings me to the dose part of it. If a patient’s having more side effects from subsequent installations of BCG, we can drop the dose of the BCG and give you less. Because what it often means is that your body’s immune system has now been sensitized, you don’t need the full dose of BCG. You can get half of it, you can get one third. Some patients can even get the same immune response with 1/10th of the BCG and keep the side effects low.

Rick Bangs:

Okay. Getting side effects is not a bad thing because it means your immune system is working and presumably working against the bladder cancer, that would be a positive?

Dr. Ashish Kamat:

Absolutely.

Rick Bangs:

Then, is there a right number of treatments?

Dr. Ashish Kamat:

You know Rick, there is no right number, but there’s an optimal number. When it comes to most of the studies that have been done, and most of the studies that have subsequently tried to dethrone, so to speak, like you said earlier, the king, which is BCG, they have not been successful if they haven’t followed what’s known as the six plus three protocol or the SWOG Protocol because it was first done by Don Lamm in the SWOG environment. That’s patients getting once a week installation for six weeks. Getting six weeks off. Getting three weekly installations times three. Then, getting three months off. Getting three installations again once a week for three weeks. Then, getting BCG every six months, three installations for a total of 36 months total, so three years. That seems to be the optimal duration and number of installations of BCG. It’s something we try to get our patients with very high risk disease to actually go through the full three-year course.

Now, if somebody has less risky disease, for example, it’s TA disease, which is where it’s in that first layer, but it’s not into the second layer or the lamina propria of the bladder, we can sometimes stop the BCG at a year, especially if the patient’s having increasing side effects or if there’s a BCG shortage because we don’t want to overtreat a patient. Even though you might have a slight improved benefit and deprive somebody else completely of the BCG, who might otherwise not have any BCG at all. The optimal duration is three years, but one year is appropriate in some patients.

Rick Bangs:

And so, you talked about cleaning the toilet area, and I know that’s a really common question. But the other common question I see online a lot has to do with sexual intimacy and that question is usually in all its forms. What are the real risks there and what must I do or know as a patient or a partner to mitigate those risks?

Dr. Ashish Kamat:

The first thing to know is that there has been no documented case that can be proven to be related to BCG of sexually transmitted disease type characteristics, so it’s not a sexually transmitted bacteria or disease. That being said, because of the fact that there is BCG, that’s clearly voided the first time the patient empties the bladder, and potentially if the patient has not had the capability to completely empty the bladder because of age, prostate related enlargement, et cetera. There might be bacteria excreted in those second and third void as well. We usually tell patients to refrain from sexual intercourse for 48 hours after the BCG installation. That’s just a precaution that’s born out of, I guess, a slight fear that what if it happens? But again, after 48 hours, it’s completely safe. Even within 48 hours, if by chance someone does have sexual intercourse, it’s nothing to panic about.

Rick Bangs:

Other forms of sexual intimacy besides intercourse, same? 48 hours?

Dr. Ashish Kamat:

Same, same, Yeah. Same 48 hours for pretty much all of it, because the thought process there is in and around the urethra the bacteria should not be present after 48 hours in any relevant concentration.

Rick Bangs:

Excellent, excellent. I know there’s a lot of people that want to have the answer to that question, so thank you. All right. Dr, Kamat, I want to thank you for your time today. You’ve given us such a wonderful insider’s look at the BCG experience. We’ve answered, I think, a lot of the most common questions that our patients are asking or even afraid to ask.

Dr. Ashish Kamat:

My pleasure, Rick. Always a pleasure to be with you and I hope this has been informative for everybody.

Rick Bangs:

I’m sure it has. If you’d like more information on BCG, please visit the BCAN website, www.bcan.org, and search for BCG. If people want to get in touch with Dr. Kamat, they can contact bcan@info@bcan.org. Just a reminder, if you’d like more information about bladder cancer, you can contact the Bladder Cancer Advocacy Network at 1 888 901 2226. That’s all the time we have today. Thank you for listening, and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thank you again, Dr. Kamat.

Dr. Ashish Kamat:

My pleasure.

Voice over:

Thank you for listening to Bladder Cancer Matters, a podcast by the Bladder Cancer Advocacy Network or BCAN. BCAN works to increase public awareness about bladder cancer, advanced bladder cancer research, and provide educational and support services for bladder cancer patients. For more information about this podcast and additional information about bladder cancer, please visit bcan.org.