Transcript of “Everything You Need to Know About Bladder Preservation with Dr. Leslie Ballas” podcast

October 23, 2023

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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’m 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.

I’m pleased to welcome today’s guest, Dr. Leslie Ballas. Dr. Ballas is a graduate of the University of Michigan and the Radiation Oncology Director for the Hematologic Bone Marrow Transplant Cellular Therapies Disease Research Group at Cedar-Sinai in Los Angeles. She’s a member of the NCI Bladder Cancer Task Force, she’s vice chair of the ASTRO Annual Meeting Scientific Committee for Genital Urinary Malignancies, and of course she’s involved with BCAN and is an editor of UroToday as part of their Bladder Cancer Center for excellence.

Dr. Ballas, thanks for joining our podcast today.

Dr. Leslie Ballas:

Thank you so much. I’m so excited to be here. I always enjoy talking to you, Rick, and talking about bladder cancer and treatment options for our patients.

Rick Bangs:

I’m looking forward to this. So at this year’s think tank, you were part of a terrific panel that was discussing the topic beyond bladder preservation. And I think our listeners will find it interesting as it builds on the Bladder Preservation Podcast we did earlier this year with Dr. Jason Efstathiou.

So I thought we could start with just a quick refresher on bladder preservation from that podcast first and then we’re going to move into your panel’s thoughts.

Dr. Leslie Ballas:

Great. Sounds perfect.

Rick Bangs:

Okay. So first, the most common treatment for muscle invasive bladder cancer is radical cystectomy. But there’s momentum building, it has been for quite some time, around bladder preservation. So what defines a treatment as bladder preservation?

Dr. Leslie Ballas:

So bladder preservation is basically keeping your own bladder or not having a surgery to remove your bladder. And so you get treatment for your cancer with your bladder intact.

Rick Bangs:

Okay. And then I always try to remind people when we talk about bladder preservation, we’re really talking about more than just the bladder because the term just seems to understate the impact.

Dr. Leslie Ballas:

Absolutely. When you have bladder cancer surgery as a male, you have your bladder taken out and your prostate and seminal vesicles, and there’s obviously reconstruction, which I’m sure you guys have talked about on this podcast, all the different options.

And so it’s avoiding any of those surgeries. And bladder preservation can be done in multiple different manners, but yes, ultimately it is the preservation of one’s native bladder.

Rick Bangs:

And so let’s walk through it from a female point of view, if you mind just reinforcing the key points on the female side.

Dr. Leslie Ballas:

Yeah, thank you. As your listeners probably know, there is a male predominance of bladder cancer of three or four to one. And so oftentimes we don’t get to talk as much about female bladder cancer and we should, so thank you.

Similarly, the surgery would allow women to keep their bladder and any of the other genital urinary or gynecologic organs that would normally be removed. And we’ll talk about this a little bit, but when we talk about bladder preservation, there is a lot of patient reported outcomes that indicate that there is better health related quality of life in patients, especially related to sexual health related quality of life.

Rick Bangs:

Okay. So there’s some different types of bladder preservation. So I hear, and this often talk about, trimodal therapy, which is commonly referred to as TMT. So can you give us a flavor for what the spectrum looks like?

Dr. Leslie Ballas:

Absolutely. So we’ll start with TMT because that’s probably the most prevalent type of bladder preservation. And you’re right, it’s trimodal therapy and that is because there are three different components to it.

The first is what’s called a transurethral resection of bladder tumor or TURBT. And that’s when a patient gets taken to the operating room and the surgeon scrapes the wall of the bladder and truly diagnoses muscle invasive bladder cancer. This then, to be part of trimodal therapy, would be followed by radiation and chemotherapy given at the same time.

That is the most well studied and longest existing type of bladder preservation. Bladder preservation can also be chemotherapy and immunotherapy, then evaluation of response to that therapy. And if there’s a complete response, no residual cancer left behind, patients can opt to save their bladder and continue on immunotherapy.

That’s a recently studied type of bladder preservation as well.

Rick Bangs:

And so today, who qualifies to get a trimodal therapy, based on guidelines?

Dr. Leslie Ballas:

So it’s patients who have muscle invasive bladder cancer, which would be, we would say clinical stage T2 to T4a. But what that really means is that it’s invaded into the muscle. It has not spread to the lymph nodes. It is urothelial cell cancer, meaning it’s from cancer cells that arise in the bladder wall or lining itself.

Rick Bangs:

And that’s the most common type, right? Urothelial?

Dr. Leslie Ballas:

Yeah, that’s exactly right. That’s the most common type. It also has to be a patient who doesn’t have swelling or enlargement of the tube that carries urine from their kidney to their bladder, what we call hydronephrosis. It’s also not for patients who have the very extensive superficial bladder cancer.

Rick Bangs:

And it seems like trimodal therapy would offer benefits in terms of quality of life. And you hinted at this earlier, so how much has that been studied and what have we found?

Dr. Leslie Ballas:

Yeah, so we do have really good long-term outcome comparisons between radical cystectomy and trimodal therapy from Mass General and the University of North Carolina. And they published this a number of years ago, and they found that when you compare in the long-term, trimodal therapy leads to better sexual function, body image, in the long term.

When we’ve looked at this more recently, the folks at Tata Memorial Hospital in India have recently done a comparison that was presented a week and a half ago at our annual meeting, ASTRO, comparing patients who’ve had radical cystectomy within ileal conduit reconstruction compared to trimodal therapy. And they found no differences in terms of quality of life except for in the area of overall sexual bother or sexual symptoms in which trimodal therapy ends up being better than the radical cystectomy with ileal conduit.

We also know that when you look at patient reported outcomes from radiation alone or chemoradiation, that during treatment the health related quality of life decreases, but by six months patients go right back to their baseline and even in some situations better than baseline depending how you go into the treatment.

And so this therapy allows you to not only keep your bladder but keep really excellent sexual function as well as quality of life.

Rick Bangs:

Which is something patients certainly appreciate.

So the NCI has a National Clinical Trials Network and a National Community Oncology Research Program, and these are particularly suited to advanced health related social needs research. And we’ve seen a lot of good stuff coming out of there, and I think we’ve talked about that a little bit in terms of clinical trials.

So I’m hearing about shorter courses of radiation for all different kinds of cancers. And is that an option under trimodal therapy?

Dr. Leslie Ballas:

Yeah, that’s a great question. Within the general field of radiation oncology, we’ve started to decrease the number of treatments across all different kinds of cancers and genital urinary cancers specifically. For bladder cancer, the most common number of treatments that we give in the US is 32 treatments and in the UK they use 20 treatments, just a little bit higher dose per treatment, fewer number of treatments.

I always tell my patients it’s like pumpkin pie. You’re going to get the whole pie, it’s just a matter if you want lots of little pieces or fewer number of slightly bigger pieces. And what they’ve found when they’ve looked at 20 treatments and compared it to 32 treatments is that it’s certainly, at least, equally effective. Some would say that the 20 may be even better. And so many people have started to use the 20 routinely in the US as well in the treatment of bladder cancer with trimodal therapy.

The one caveat would be that over the past number of years we’ve been accruing to this wonderful trial through the SWOG NRG cooperative groups that has looked at comparing trimodal therapy in the traditional way that we described, the TURBT plus radiation and chemo, compared to trimodal therapy, TURBT, radiation and chemo with immunotherapy.

And that trial has accrued like gangbusters, it’s going to be the largest accruing bladder preservation trial, I think, ever. And on that trial, they only allowed the radiation to be given in 32 treatments because of some concerns about increased side effects with the fewer number of treatments and the immunotherapy.

And so just for our listeners, in case you were treated on that trial or get offered to be treated on that trial and you don’t get offered the 20 treatments, that’s the reason why. And I think that it is just to be extra cautious because of the immunotherapy that’s involved with that clinical trial.

Rick Bangs:

Right. So during your think tank panel, you covered some context where the use of radiation, either alone or in combination with chemotherapies, gaining momentum or maybe one day would find their way into a clinical trial. Talk about those contexts.

Dr. Leslie Ballas:

Yeah, absolutely. We talked about, as you indicated, the use of radiotherapy beyond just this trimodal therapy that we’ve been talking about. There’s tons of opportunities for therapy along the continuum of the bladder cancer spectrum.

Obviously we do everything we can to cure a patient of their bladder cancer upfront with either neoadjuvant chemotherapy and radical cystectomy or trimodal therapy. But unfortunately some patients recur or some patients have metastatic disease and there are plenty of uses for radiation, as you said, either with chemo or without, beyond the upfront treatment across the spectrum of bladder cancer.

Rick Bangs:

Okay. So can we talk about bladder cancer recurrence after radical cystectomy or chemoradiation, because sometimes patients have that? What’s the current role of radiation here and what would you foresee in the future if you’ve got out your crystal ball?

Dr. Leslie Ballas:

So, if a patient has had a radical cystectomy and they recur in the pelvis, meaning either in a lymph node or in the area where the bladder used to sit, then radiation is an option. We can give radiation either with or without chemotherapy and focus it on the area of recurrence.

And even in patients who get a neobladder, there is the potential to give radiation to the pelvis. There’s been a lot of hesitation on the part of radiation oncologists and surgeons in the setting of a neobladder to give radiation to the pelvis because here you are asking this piece of bowel to do different things and what if you expose it to radiation?

While I was at USC prior to joining the faculty at Cedars, we evaluated our patient population in conjunction with a group in France to see about radiation to the pelvis in the setting of a neobladder. And we found that in the right context to the right dose, it is safe.

And so, that is something to always remember.

Rick Bangs:

Is some of this the continuing advancement of radiation therapy?

Dr. Leslie Ballas:

Absolutely. So that’s a really great question. In the olden days where we used to… Which is probably like 20 plus years ago. 15, 20.

Rick Bangs:

My vintage.

Dr. Leslie Ballas:

Yeah. No one can see me, but I am not that young. But anyway, in those days the radiation used to come from the front, from the back, from the sides, just sort of in those four different positions. And after you have your bladder taken out, your small bowel falls into your pelvis. And so when we would give radiation after radical cystectomy, there would be a lot of gastrointestinal toxicity, diarrhea mostly, because the bowel was getting exposed to high doses of radiation.

Rick Bangs:

Right.

Dr. Leslie Ballas:

Nowadays, radiation can come from a 360 degree arc all around your body from all sorts of different points that converge on a target, let’s just say recurrence in the pelvis, but can be sculpted to avoid normal surrounding tissues like the neobladder, like the small bowel.

And so the side effects from postoperative radiation have really decreased given technological advances with radiation.

Rick Bangs:

So a lot more precision, it sounds like.

Dr. Leslie Ballas:

Yes, that’s exactly right.

To get back to the question that you asked before, just to make sure that I hit on it, we talked about after radical cystectomy, there’s the role for radiation if there is a recurrence in the pelvis.

After chemoradiation, this becomes a little bit more nuanced. We don’t typically reradiate the bladder. So if someone got radiation as part of a trimodal therapy to their bladder upfront, we wouldn’t typically reradiate someone’s bladder because of the toxicity that that could cause, or the side effects might be too great.

However, you can use radiation even if someone has had the trimodal therapy. If a patient, god forbid, fails or has a recurrence in one of their lymph nodes and that’s outside of the area that got prior radiation. And so I would say that there’s no blanket statement to say we definitely can give radiation after trimodal therapy, but there are specific cases where it can be done if it’s like a specific scenario.

Rick Bangs:

Okay. All right. So there was another context in the think tank session and that was patients who have one or more lymph nodes. And you mentioned some criteria up above that, previously, that didn’t include that.

So if we’ve got one or more lymph nodes and they’re positive and sometimes called positive nodes, and we discussed positive nodes with Dr. Seth Lerner in Episode 52, if people want a refresher. So this stage is commonly referred to as advanced bladder cancer.

So traditionally, what are the options for those patients and what’s appropriate from a bladder preservation perspective there both now and maybe even in the future?

Dr. Leslie Ballas:

So I think it’s really important to understand that these lymph node-positive patients were never included in the clinical trials that established equivalents between TMT and radical cystectomy. And so, they sort of present a conundrum because they do better in terms of their outcomes, their cancer outcomes, than patients who have disease spread beyond the lymph nodes to different areas of the body metastatic disease. But they don’t do quite as well as the patients who have their disease confined to their bladder.

And so the National Cancer Care Network, the NCCN lists multiple options for these patients. Most typically they start with a neoadjuvant chemotherapy approach because the idea is once it gets out of the bladder, there’s obviously cancer cells that are either in the lymphatics and that’s how they get to the lymph nodes or possibly cells you can’t see in the bloodstream.

And so the neoadjuvant chemo is meant to address the body globally. And then following that, if the patient has a response, you can either get a radical cystectomy or you could get TMT. And both are options within the NCCN guidelines.

Now, this has been in the guidelines for a while, but it’s actually just this year that we had some pretty good data from the UK where four centers looked in a retrospective fashion, or looked back at their experience, of what to do in the lymph node-positive patient and compared should you get radical cystectomy, should you get trimodal therapy, as the local treatment after the neoadjuvant chemo.

And what they found was that when you do TMT, so a combination of chemo and radiation, that there’s really no difference in overall survival between that and radical cystectomy in the lymph node-positive patient population.

And so really that patient population, if they’re going to get local therapy, should also be given a choice. And many would argue that the benefit of trimodal therapy and preserving the bladder is really quite great in this patient population because as you’ve discussed I’m sure on this podcast, the radical cystectomy and reconstruction is a big operation.

Rick Bangs:

Oh, yeah.

Dr. Leslie Ballas:

I know. And in patients who have disease that’s outside of just the confines of the bladder, maybe they don’t need to get their bladder taken out and undergo that large operation when they may have microscopic spread that hasn’t been caught yet by imaging.

Rick Bangs:

So these findings, this is a big deal.

Dr. Leslie Ballas:

Yeah, it is. It was in the Journal of Clinical Oncology, so one of our high level journals. And it was, again, this retrospective study from four centers in the UK and is great data for us to have to really inform patients with lymph node-positive disease.

Of note, there’s also a clinical trial that is currently accruing. It is a trial through one of the national cooperative groups, ECOG Akron, that is looking at what to do with lymph node-positive patients. And it’s specifically aimed at bladder preservation. So it’s prospective meaning we’re taking patients when they get diagnosed, they almost everyone gets neoadjuvant chemo. And then there are some options offered that all involve bladder preservation.

And so, that’s a great trial in a patient population where we really need data to inform how we treat people.

Rick Bangs:

Excellent. All right, so let’s talk about the patient who’s metastatic. So in that case, the bladder cancer has gone beyond the bladder and it’s gone beyond the nearby lymph nodes, right?

Dr. Leslie Ballas:

Yeah, that’s exactly right.

Rick Bangs:

So this is a particularly challenging diagnosis. So why is that challenging?

Dr. Leslie Ballas:

It’s challenging because once the disease has spread beyond the pelvic lymph nodes or spread into distant organs like bone or lungs, the treatment that we offer is not curative in its intention. Meaning we’re offering treatment to try to perhaps prolong life, make people feel better, but it’s not curative.

And so, we know from the cancer.gov or the American Cancer Society statistics, that five-year overall survival for patients with metastatic disease is commonly less than 10%, which is very different from the advanced bladder cancer patients who have five-year overall survival much closer to 40%.

And so it becomes a much more challenging situation.

Rick Bangs:

I mean, the analogy that I often think about is as the cancer gets more advanced, it’s like it gains superpowers, right? And so you’re not just dealing with one superpower, you’re dealing with more and more superpowers.

Dr. Leslie Ballas:

Okay. Yeah, I think that’s a great analogy. I like that.

Rick Bangs:

Yeah. What are my options going to be as a metastatic bladder cancer patient?

Dr. Leslie Ballas:

The backbone of your therapy would be chemotherapy and/or immunotherapy. There’s lots of advancements currently looking at different kinds of newer drugs, but it is a drug-based treatment.

Rick Bangs:

Okay. All right.

So the next context for your bladder preservation group at the bladder cancer think tank has what is, from a patient perspective, a strange name, oligometastatic bladder cancer. So what is that and how might we use radiation there?

Dr. Leslie Ballas:

Yeah, it’s not just a strange name for patients, actually. It’s a term that has become very popular recently amongst cancer physicians. Oligometastatic bladder cancer is when you have typically five or fewer sites of metastatic disease. And the idea is that you’re catching the metastatic disease early. It hasn’t spread to a lot of different places, it’s only in just a few places.

And so the idea is if we’re catching it early, maybe if we offer metastasis-directed therapy, radiation, to these few sites of disease and eradicate all the sites that can be seen, that we can improve oncologic outcomes. And the reason that we think this is because in other genital urinary cancers such as prostate cancer, there have been quite good outcomes using ablative radiation.

And here’s another amazing term or lingo for you, which is SBRT, which stands for stereotactic body radiotherapy.

Rick Bangs:

Oh, boy.

Dr. Leslie Ballas:

I know, right? All it means is that we give really, really focused high dose, fewer number of treatments. And the idea is for it to truly be ablative, not just kill the cancer cells, but maybe even kill the vessels or the blood supply that feeds those cancer cells.

And this technique has been used for oligometastatic disease, as I mentioned in the prostate, it’s been used in renal cell. And so there’s been some evaluation of how this could be used in bladder cancer patients as well. And we really have only a few smaller studies that have looked at this. But we can get, we know, good local control of the treated metastatic foci, which is doctor speak for saying we can do a good job killing this cancer cells in these few sites of disease.

But ultimately the question is, but what does that mean globally? And we know that patients, their ability to control the disease more globally once they have the treatment, the SBRT or that ablative radiation, is reasonable.

When we look at retrospective data, we know that patients do best when they get treatment to one metastatic site as opposed to greater than or equal to two metastatic sites, which makes sense. The fewer number of cancer sites that you have, the fewer number of cancer sites that the radiation has to kill, the better patients will do.

And so that is an area that is certainly being evaluated for future study, and one that is gaining momentum in terms of interest within the bladder cancer community. Of note, there’s one other situation in metastatic disease where there’s some research being done to look at whether if you have metastatic disease, is there any benefit of giving some radiation to the bladder if it’s still in the body?

So let’s say somebody presents, gets diagnosed with metastatic disease upfront. They still have their bladder in their body and they’ve got disease beyond the bladder, is there any benefit to radiating the bladder itself? And there has been some very small but early studies saying that there might actually be some benefit in radiating the bladder itself in that setting.

And so all I can say about that is it’s sort of a, let’s stay tuned and see what the research community develops and tests. But clearly we are looking at using radiation most commonly in conjunction with either chemotherapy or immunotherapy in these later stage bladder cancer patients.

Rick Bangs:

Yeah, because always controversial. Once it’s metastatic, it’s always controversial about what you can do that would be meaningful and important relative to the original site, which would be the bladder. So that makes sense.

All right, so last context from your think tank group is post neoadjuvant chemotherapy. So I had the neoadjuvant chemotherapy. After that I’ve been diagnosed with muscle invasive and most commonly after the neoadjuvant, I would’ve radical cystectomy. So what can this patient expect in the future?

Dr. Leslie Ballas:

Rick, you’re asking my favorite topic. I love to discuss this topic because it’s an area that we are currently developing a trial through the Southwest Oncology Group, through SWOG, to evaluate this exact question, because oftentimes patient will get the neoadjuvant chemotherapy with the intention of going on to cystectomy, and then they have a good response.

And they’re like, “Hey, can I save my bladder now?” And it’s a highly motivated group of patients who we just really don’t have a great paradigm for them. And so we know, based on earlier data, that you don’t need neoadjuvant chemo before you get trimodal therapy. They studied that back in the 1980s and nineties and found that the neoadjuvant chemo wasn’t needed to provide additional benefit.

And even more recently, there’s been some data showing that it doesn’t necessarily improve outcomes. And so the question is, one, is that just because it’s older data with chemotherapies that aren’t used as much anymore? Or where radiation techniques were different. Or is it truly maybe something that patients could benefit from?

And so this is an area of active research because, again, there are a lot of patients who do really well with neoadjuvant chemo and then either because they weren’t offered TMT upfront or because they are excited about their response, want to save their bladder. And so I think that you hit the nail on the head with asking about this patient population and what we should do for them.

Rick Bangs:

Yes, I think this is such a critical area.

Okay, so any final thoughts?

Dr. Leslie Ballas:

I think ultimately the whole point of the panel discussion and what I hope to get across in this podcast is that radiation can be used upfront as the definitive or curative modality as an option in the treatment of bladder cancer. But it can be used at lots of different points also along a patient’s journey, whether they have a recurrence in the pelvis, whether they have a few number of metastatic disease points outside of the pelvis.

And something actually we didn’t talk about, which is always an extremely important component to cancer care, is for palliation. Patients oftentimes later in their disease trajectory, have disease maybe in a bone or maybe somewhere that’s causing them pain. And radiation is exceptionally effective in relief of pain for patients without some of the side effects that come with prolonged narcotic use, such as fatigue and nausea and tiredness.

So I just really want to emphasize that there’s lots of different places that we can incorporate radiation for bladder cancer patients, and each of them offers a unique time point in the course of disease where we can be offering something meaningful with hopefully meaningful endpoints for patients.

Rick Bangs:

Excellent. So we’re going to stay tuned and patients should probably always ask about the possibility.

Dr. Leslie Ballas:

I think that’s a good plan.

Thank you so much for having me. This was wonderful. You’re a great podcast host. Claps for you.

Rick Bangs:

Thank you. Thank you.

So Dr. Ballas, I want to thank you for sharing your perspective on the promise of bladder preservation as a viable option for many patients, and we will stay tuned on that.

If you’d more information on bladder cancer, please visit the BCAN website, www.bcan.org.

Just a reminder that 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. Be sure to like, comment, and subscribe to this podcast so we have your feedback.

Thank you for listening, and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again, Dr. Ballas.

Dr. Leslie Ballas:

Thank you.

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.