New bladder cancer treatment would keep the organ intact

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

A new targeted therapy might be an option for some patients with high-risk bladder cancers who would rather not have their bladders removed.

Here to tell us about this new treatment is Dr. Joseph Jacob. He's an associate professor of urology, specializing in urologic oncology.

Welcome back to "The Informed Patient," Dr. Jacob.

Joseph Jacob, MD: Thank you for having me.

Host Amber Smith: You recently spoke to other urologists about this new treatment in a presentation at the American Urological Association's (AUA) annual meeting. But before we get into the details, can you explain which specific patients this could help?

Joseph Jacob, MD: These are for patients that have bladder cancer -- there's a spectrum of types of bladder cancer -- these are patients that have superficial bladder cancer, meaning that the bladder cancer is not invading into the muscle of the bladder. So Stage 1 bladder cancer (has not yet invaded muscle tissue) and below.

And these are usually patients that have already had multiple treatments. We call them intravesical treatments, or treatments that are placed inside the bladder. And so these are patients that are, we call it, "= "unresponsive," or you may hear "refractory" or "resistant," but we call it unresponsive to bladder treatments. And the most common one being BCG, and we can talk about that more, but BCG is a tuberculosis vaccine that's like standard of care for superficial bladder cancer.

Host Amber Smith: When you say superficial, does that necessarily mean that it was caught early?

Joseph Jacob, MD: Well, the technical term would be "non-muscle-invasive."

And so, as urologists, we talk about non-muscle-invasive bladder cancer, but just for simplicity's sake, if you hear me say "superficial," it just means it hasn't invaded into the muscle. It's tough to tell whether this is caught early or not; 70% of bladder cancer is non-muscle-invasive, so it may just be how the disease behaves, or it may just be earlier in the process. It's kind of difficult to say.

I will say though, some of these tumors can, if left untreated, can become muscle-invasive. And so that's one of the reasons why this therapy is filling such a high need, is that after BCG, there's not a lot of options besides removing the bladder. And if you don't act, if you don't take the bladder out, or if you don't supply effective salvage therapy, then these patients can progress to muscle-invasive bladder cancer.

Host Amber Smith: And are we talking about male and female patients?

This could be for either?

Joseph Jacob, MD: Yes. So male and female patients.

Definitely more men have bladder cancer; it's about 3 to 1, but one interesting thing is that when women do get bladder cancer, it usually tends to be more advanced because they just think that the blood in the urine's from a urinary tract infection, or maybe their primary care (provider) just gives them antibiotics, and then, after multiple rounds of antibiotics. ...

So they do tend to have a delayed diagnosis as compared to men.

Host Amber Smith: Well, let me ask you about the term "non-muscle-invasive," or "muscle-invasive." Is the bladder the muscle that we're talking about?

Joseph Jacob, MD: Yeah, yeah. The bladder is basically a muscle that squeezes, and so the brain, through the spinal cord and nerves that attach to the bladder, basically tells your bladder to squeeze or not to squeeze.

There's different layers of the bladder. the deep layer is the muscle. That's the main function of the bladder. But then there's like connective tissue, and then there's another layer that's called the mucosa, and think of that layer as almost like a smooth layer, like the inside of your mouth. And so that's sort of how we stage bladder cancer. So, mucosa is like the first layer. That's the shiny, superficial layer. That would be stage Ta (early), that would be superficial.

Once it gets into the connective tissue, or we call it the lamina propria, that would be stage T1. And then the next layer would be the muscle or the detrusor muscle -- you may hear that that's the bladder muscle -- and that would be stage T2.

And so the reason why that matters -- staging in bladder cancer really, really matters -- the reason why it matters is, Stage T2, or muscle-invasive bladder cancer, the type of treatments that we put inside the bladder, like the intravesical therapies, they don't work. Really, the treatment changes drastically.

So once you have muscle-invasive bladder cancer, this is a disease that can spread, or we call it "metastasize," into the bloodstream. And this is something that can be very dangerous, and at that point it becomes a life-threatening disease.

And so we usually do things like chemotherapy. We do things like removing the bladder or irradiating the bladder. So it's a very different approach.

So when you have patients that have non-muscle-invasive bladder (cancer), basically the goal is to save the bladder, to prevent the superficial cancers from progressing or becoming more aggressive and becoming muscle-invasive bladder cancer.

Host Amber Smith: So where does the BCG get used? Is that if you don't have any muscle involvement?

Joseph Jacob, MD: Exactly. Exactly. Non-muscle-invasive bladder cancer.

There's also grade. So there's stage, and there's grade. Grade is basically: How ugly does the tumor look? And if it's high grade, that means it's aggressive and ugly looking. If it's low grade, it's non-aggressive and doesn't look as ugly. So usually in patients with high grade, meaning that those high-grade patients, those ugly-looking cancers, can have more of a chance of becoming more aggressive and more of a chance of becoming invasive, more, invasive.

So BCG is a vaccine. It's one of the first vaccine therapies. We've been using BCG since the '70s, believe it or not, and it's been the best thing ever since. And it's probably one of the most common things that urologists use in their clinics.

It's a live, attenuated, means not as infective, bacteria, tuberculosis bacteria, that's put inside the bladder, and it tricks your own immune system, the immune system of the bladder, into fighting the bladder cancer. And the success rate's probably in the range of 60%. So people do well with it, but not everybody does well with it. And so there's a good number of patients that become, we call it unresponsive, so they're non-responders to BCG, and then you're left with a situation where: Now what do you do? You hate to remove the bladder. It's not muscle-invasive disease, but you don't have a lot of options available to you.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith.

I'm talking with urologic oncologist Dr. Joe Jacob, who takes care of patients with bladder cancer, and he's telling us about a new targeted therapy that might be an option for some patients with high-risk bladder cancer.

Now, if I understand correctly, this is called TAR-200. What can you tell us about it?

Joseph Jacob, MD: This is a paradigm-shifting treatment. What I mean by paradigm shifting is, we've never really treated bladder cancer like this before. So what this is, is a device, you can almost think of it as like a drug delivery device. It's a silicone, soft pretzel, it looks like a pretzel, and you can straighten it out, and you can put it through a catheter (hollow tube), and you sort of deploy it in the catheter. It's about a 30-second procedure in the clinic, just like putting a catheter in. And then this device is deployed, and it delivers sustained-release gemcitabine. Gemcitabine is a chemotherapy that we use often in bladder cancer.

The cool thing about it, the novel thing about it, is that, for example, when we give BCG in the bladder, patients hold it an hour, two hours at the max. Some patients can only do 30 minutes.

But the whole idea behind this TAR-200 device is, it floats in your bladder, and it gives a steady dose of chemotherapy inside your bladder for about seven days or more. And so you can see the huge difference between the amount of time the bladder cancer is exposed to drug. And we think that's one of the reasons why this is performing so well so far in the clinical trials.

Host Amber Smith: So it's meant to get rid of the cancer cells and preserve the bladder all at the same time.

Joseph Jacob, MD: Exactly. So it's doing what we've been trying to do, but it's just doing it for a longer period of time.

So it accomplishes two things, right? It delivers a steady dose of chemotherapy into the bladder, and it delivers it exactly where it needs to go. It's sitting right there in proximity to these tumors. And it's letting these tumors see chemotherapy for a much, much longer period of time than we've ever been able to treat these patients.

Host Amber Smith: How many patients from Upstate have been participants in the clinical trial so far?

Joseph Jacob, MD: There's a few clinical trials that we've been participating in. If you combine all the trials, we've probably had, oh, we've probably had in the range of like 15 to 20 patients, which is probably one of the top sites in the country, as far as how many patients we've put on some of these trials.

Host Amber Smith: Can you tell us about the response rate for these patients and what has worked well for them?

Joseph Jacob, MD: Yeah. So I can share what I presented at the AUA. By the way, the AUA was well attended this year. This is because this is such a new drug, and this is going to be something that's practice changing. There were a lot of people that wanted to hear the data, and not just urologists, but there were all different types of people, that wanted to hear the data.

But I digress. So, if you talk about complete response rate, what does complete response rate mean?

You have these patients that have gotten multiple treatments of BCG. These are classically a very difficult population to treat because they're just not responding. The tumor is already resistant to immunotherapy. And so the response rates have not been great, if I can just tell you.

So what's out there?

Most drugs are anywhere in the range of like 15% to 25% response rate so far, of what we have approved. And what we mean by complete response, meaning you give the treatment, and then you look in, and you do biopsies, and there's no cancer left.

So not only do you look in and not see bladder cancer, but you actually have to do biopsies of the bladder at six months, and there's no cancer left. And so when you look at the complete response rate, and you compare it to 15% to 25%, the complete response rate was almost 83%.

Host Amber Smith: So that's unheard of, it sounds like.

Joseph Jacob, MD: Yeah, and you know, when I was talking to people about it, I said, "Look, these are blockbuster numbers." Like we just haven't seen anything perform like this before.

Host Amber Smith: What else did you look at besides just plain survival?

Joseph Jacob, MD: We didn't look at survival. Well, one of the secondary endpoints was survival, but you don't expect these patients to have any kind of survival issues. I mean, this is a patient population that you're trying to prevent them from losing their bladders, but they're not a patient population that you're going to be worried about cancer-specific survival, that kind of thing.

Cancer-specific survival in this population was like 100%. And it's still early. I mean, it's still like within the first like couple years of following these patients, and not everyone's made it out to two years, so it is still early. But if you look at what we really care about in this group are like how many patients are getting cystectomies, meaning bladder removals?

And you want to know like how many patients are responding, because the number of patients that are responding is a good predictor of how patients are going to do in the future.

Host Amber Smith: Are there side effects or precautions to be aware of?

Joseph Jacob, MD: Overall, well tolerated. Patients do pretty well with it. Most side effects are expected. You have a foreign body in your bladder, so your bladder's not going to feel amazing. And I've had some patients that don't notice it, and I've had some patients that really, really do notice it.

But really, the most common side effects would be things like frequency, urgency, pain. So frequency means peeing a lot. Urgency means like when you have to pee, you really, really feel like you have to pee. Dysuria means when you pee, it hurts. Those are the most common side effects, and those are pretty standard with any kind of treatment, even BCG, or anything we put in the bladder, patients usually have bladder symptoms.

Host Amber Smith: At this point, is this a valid option for patients, or do they have to join a clinical trial still? Like at what point will it be finished?

Joseph Jacob, MD: It's still part of a clinical trial. It's not technically FDA (Food and Drug Administration) approved yet. We have a few trials open here, but probably, I'm guessing, in the next year we'll have approval.

Host Amber Smith: Would this likely replace BCG? Would you do this before you even use the BCG?

Joseph Jacob, MD: That's a great question. So the trial that I presented, it was post-BCG, so it was after BCG. That's a very difficult patient population to treat, so I think it'll get approved in that setting.

There is another trial that we have open that is a pretty exciting trial. It's going head to head, it's competing versus BCG. So it's in patients that have never received any treatment, first diagnosis, and you either get BCG, or you get TAR-200. So that'll be interesting. Those results, we haven't seen any numbers yet, but that'll be very interesting. Maybe we can talk about it in a year or so.

Host Amber Smith: Oh, it is very interesting, and I'm really grateful that you made time to tell us about this, Dr. Jacob. Thank you.

Joseph Jacob, MD: Absolutely. My pleasure.

Host Amber Smith: My guest has been Dr. Joseph Jacob. He's an associate professor of urology, specializing in urologic oncology at Upstate.

"The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe.

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