Transcript of Is Bladder Preservation Right For You?

June 20, 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. This podcast is sponsored by the Seagen/Astellas alliance.

I’m pleased to welcome today’s guest, Dr. Jason Efstathiou. Dr. Efstathiou is Professor of Radiation Oncology at Harvard Medical School, Vice-Chair for Faculty and Academic Affairs and director of the Genitourinary or GU division in the Department of Radiation Oncology and clinical co-director of the Claire and John Bertucci Center for GU Cancers at Mass General. He is an internationally recognized leader in the field of GU malignancies and radiation oncology. His research has informed clinical guidelines and made novel contributions to organ preservation therapy for bladder cancer, as well as global oncology outreach efforts. Dr. Efstathiou holds multiple leadership and board positions within professional societies, including serving as recent past chair of the Genitourinary Cancer Symposium, GU ASCO within patient advocacy organizations such as BCAN within the NCI where he previously served as co-chair of the Bladder Cancer Task Force and within our GU Oncology where he is the vice chair of the GU Steering Committee and bladder lead. Dr. Efstathiou, thanks for joining our podcast today.

Dr. Jason Efstathiou:

Thanks so much Rick. Wonderful to be here. And please do call me Jason.

Rick Bangs:

All right, thanks. All right. So as many of us know the most common treatment for muscle invasive bladder cancer is radical cystectomy, but there is an alternative that’s gaining some momentum known as bladder preservation. So can you talk to us a little bit about what is bladder preservation?

Dr. Jason Efstathiou:

Absolutely, Rick. I think as many know, there’s been a real paradigm shift in cancer care, contemporary cancer care and organ conservation has become much more commonplace. We certainly know that in diseases like breast cancer and anal cancer and limb sarcomas, and that’s what bladder preservation’s getting at. In terms of bladder cancer. As you noted, radical cystectomy has been the most common treatment for patients with muscle invasive bladder cancer. And many patients certainly do well with a cystectomy and you, Rick, are a wonderful example of that. But we also know that it’s a major physiologically challenging surgery and for some it can be really life altering. And so the goal of bladder preservation is to offer an alternative for suitable patients with really the goal being keeping the bladder, sparing the bladder. So this is often called bladder sparing therapy or bladder preserving therapy. Another term that’s commonly used is trimodality therapy.

And the tri in trimodality therapy really refers to the three components of bladder preservation. The first is a good resection of the tumor from within the bladder without removing the bladder and trying to do that as completely as possible. And then that is followed by a combination of radiation therapy and chemotherapy given at the same time, let’s call it chemo radiation. And the idea of that trimodality of therapy is to give patients a chance to spare their native bladder, to keep their native bladder intact. And so, that’s really what bladder preservation is getting at.

Rick Bangs:

So is there any difference between the term bladder sparing and bladder preservation or is it the same thing that they’re talking about?

Dr. Jason Efstathiou:

It’s the same thing. Bladder conserving, bladder sparing, bladder preserving, they’re all get getting at the same concept.

Rick Bangs:

Okay. And so that term really kind of understates the impact on the patient. There’s more going on than sparing or preserving a bladder in this treatment.

Dr. Jason Efstathiou:

That’s right. Of course, we’re focusing on keeping the bladder, but as you well know, a radical cystectomy does remove other organs. So for example, in men it would include the prostate, lymph nodes are also dissected and removed during a radical cystectomy and small bowel is removed often in order to create a urinary diversion. You referred to having, for example, a neobladder, there’s other diversions like ileal conduits that utilize bowel, basically. And certainly in women it’s not just the removal of bladder either. It can be the removal of the uterus and the adnexa and the anterior vaginal wall. So I think you’re right, it’s more than just the bladder.

Rick Bangs:

And so you mentioned trimodal therapy as a type of bladder preservation, but in 2023, are there other types of bladder preservation maybe including immunotherapy or some other regimen?

Dr. Jason Efstathiou:

Yeah, it’s a good question. I think that there’s a lot of study of alternative forms of bladder preservation. I think the experience is strongest and longest for the trimodally therapy that I referred to. But for example, in select circumstances and genetically favorable mutational backgrounds, there’s been some investigation of using chemotherapy alone. There’s also, of course, a partial cystectomy where just a portion of the bladder is removed, not the whole bladder, but that’s really an option for very, very selected group of patients. So again, I think the best data available and the longest history to date in the world of bladder preservation probably applies to trimodality therapy. There there’s also some series that have looked at just doing that resection within the bladder and maybe combining it with chemotherapy and trying to avoid radiation. But again, I think that that would really apply in very select circumstances.

Rick Bangs:

Okay. So tell us a little bit about the history because I know Bill Shipley from Mass General was part of the US movement toward bladder preservation, but talk to us a little bit about the history of bladder preservation.

Dr. Jason Efstathiou:

Sure. I think bladder preservation, at least in the United States, really started to take off in terms of investigation, there being studies national protocols in the 1980s, in the later eighties. And you’re absolutely right. Dr. Bill Shipley from Mass General Hospital has really been the US-based pioneer of bladder preservation therapy and had been beating that drum for a long time. So that’s really when you start seeing national protocols and studies, really in the 1980s, the later eighties and the nineties, and certainly that has continued through to today. So you’re looking at a solid 30, 40 year history, I think, in the US. So it’s not a new treatment per se. Yes, there are some other countries that do bladder preservation as well. I mean, it’s routinely used in the United Kingdom, for example, where even up to 50% of patients may go down a bladder preservation route versus cystectomy.

But even within the UK you see real regional differences in its usage. But outside of that, in the rest of the world, it’s not that commonplace to be honest. And so what I have noticed, however, is that there’s been a real tipping point in the last few years, a real growing acceptance of bladder preservation, trimodally therapy as a good alternative for the right patient for suitable, selected patients as opposed to cystectomy. And I’m seeing that greater acceptance within the urologic community. I’m seeing greater awareness from patients about the option. There’s been growing acceptance by national guidelines, heralding it as an option so the tide has turned.

Rick Bangs:

Yeah. And we’re all the better for it because I remember asking about bladder preservation when I was diagnosed in 2006 and it wasn’t an option for me. So we’ve come a long way since then. So who can get bladder preservation and who can’t?

Dr. Jason Efstathiou:

Great question. We recently ran a study, and I can get into that a little more later perhaps, but looking at large cystectomy series and databases and probably about 30% of muscle invasive bladder cancer or around that number may be eligible for bladder preservation therapy. So selection is important. And so it’s not for everybody, but like I said, it could be an option for even up to a third of patients, but selection is important. So in general, the ideal bladder preservation therapy patient is a patient who has a unifocal tumor, so maybe not multiple large tumors in the bladder, but a unifocal tumor that’s say under seven centimeters in size, that’s of what we call urothelial carcinoma or urothelial histology. So there are some other types of subtypes of bladder cancer that may not be, for example, the best fit, but the more garden var variety urothelial carcinoma seems to be a good fit.

Patients who don’t have hydronephrosis or what’s blockage of a kidney where there’s blockage backed up in a kidney, where there isn’t too much what we call carcinoma in situ. So that’s another feature of a type of bladder cancer that sometimes isn’t best served by radiation based therapies. So as long as there’s not too much carcinoma in situ, there’s no hydronephrosis. The tumor is let’s say less than seven centimeters. Urothelial carcinoma, ideally unifocal not in many tumors throughout the bladder. Ideally a tumor that can be maximally resected visibly by the urologist with that resection that I refer to what’s called a trans urethral resection of bladder tumor or a TURBT. These are the patients that are best candidates.

Those where the tumor factors, the cancer factors are offer some word of caution towards proceeding with bladder preservation may be when there’s an inability to achieve a complete resection when there is hydronephrosis, for example, the blockage of the kidneys on both sides. When there’s a large tumor burden involving the majority of the bladder. When there’s extensive or diffuse carcinoma in situ you that I was referring to. And in some other situations as well, those situations may not be ideally suited for bladder preservation.

Rick Bangs:

Okay. And you mentioned maximal TURBT, the trans urethral resection of the bladder tumor. So if I get treated in the community and I have a TURBT, could I assume that it was maximal or is maximal something that has to be done and it’s not the norm?

Dr. Jason Efstathiou:

It’s a great question, Rick. I mean, a TURBT is actually a very nuanced procedure, surgical procedure. And to actually resect the tumor deeply to get to the muscle and to get it all out and to get to the fat layer but not go too far, requires skilled surgery. There’s no two ways about it. Often for patients that we see in our clinic, we recommend a second TURBT to confirm a maximal what we call, ideally visibly complete resection. So it’s not uncommon for patients who choose to go down a bladder sparing route to have to go through two TURBTS to kind of inform that and to achieve that maximal resection.

Rick Bangs:

Okay. All right. That’s helpful. All right. So I think based on the types of treatments that you’re getting as part of this, or you’ve got this umbrella called bladder preservation in this at least three components, typically. It sounds like there’s going to be more than one kind of specialist that I should be dealing with. So can you talk about the specialist that I would be seeing?

Dr. Jason Efstathiou:

Yes. Multidisciplinary care is key here. And I would say for all muscle invasive bladder cancer patients, whether those patients are good candidates for bladder preservation or not, multidisciplinary care is key. Even if proceeding with a radical cystectomy, there’s often the discussion of the use of neoadjuvant chemotherapy that is asking for multidisciplinary care. And certainly, with bladder preservation, you need to find your, what I like to call, your stream team, that dream team that includes a urologist, a radiation oncologist, and a medical oncologist because they all play an important part in the care and delivery of that treatment.

So that is very key that you find a team that works well together, but it is those disciplines. Urology who is often diagnosing the bladder cancer and is going to perform that visibly complete TURBT and is going to follow the patient lifelong with cystoscopy, cystoscopic surveillance. The radiation oncologist who’s going to design and deliver the primary local therapy, which is the radiation therapy to the bladder and bladder tumor. And the medical oncologist who’s going to work hand in hand to deliver the chemotherapy that goes along with radiation and sometimes also neoadjuvant or adjuvant chemotherapy.

So those are the disciplines involved, and again, you want to feel that you are in good hands and finding that good team is key.

Rick Bangs:

Excellent. Okay, so now I want to talk about something that I know you were involved in, and it’s a recent publication and it’s really exciting because it talks about bladder preservation and it’s effectiveness. So can you tell us a little bit about this study? I think people are going to be fascinated by this.

Dr. Jason Efstathiou:

Absolutely. Thanks, Rick. Wonderful collaboration just led to a very important paper in a big journal called the Lancet Oncology. It was a collaboration between three centers, so Mass General where I’m at, Toronto Hospitals, namely Mount Sinai and Princess Margaret Hospital and the University of Southern California in LA. So it was Boston, Toronto, and LA. And the key thing there is, well, yes, Mass General has decades long his history with trimodality therapy as we discussed. Toronto introduced a multidisciplinary bladder cancer clinic in 2008 where all patients with muscle invasive bladder cancer have the options of cystectomy and trimodality therapy discussed with them in kind of the fashion that I was describing. And that that’s very similar again to what we do at Mass General. And then University of Southern California, which has a storied history in bladder cancer and is a very high surgical volume center, maybe the highest in the country in terms of radical cystectomies and expert surgeons that are doing radical cystectomies.

So it was the wonderful merger of centers with strengths in these treatments and ability to offer these treatments. And so those centers got together and pooled patients that have gone either through radical cystectomy with or without neoadjuvant chemotherapy or trimodality therapy. And lo and behold, the data from this really is probably the best available comparative data, a randomized trial comparing these treatments was attempted in the UK but failed to bring in enough patients, failed to what we call, accrue. And if the UK can’t run a randomized trial, really it’s probably not going to happen. Okay. And so there is no randomized trial that’s planned, and therefore this study, this collaboration between these three institutions probably is the best available comparative data. And some are even arguing it may be the best data that will ever be available if no randomized trial can be done.

So the short of it is that there was no difference in terms of cancer outcomes, in terms of survival from bladder cancer or the incidence of metastatic disease spread of the cancer. They were exactly the same between the cystectomy and the bladder preserving chemo radiation trimodality therapy. And this was after candidates that are eligible for both treatments were pooled together and matched. And so it was statistically a very well done study. And at the end of the day, the results from it support trimodality therapy in the setting of multidisciplinary shared decision making as we’ve already discussed and supports that trimodality therapy should be offered to all suitable candidates with muscle invasive bladder cancer, and not only to patients with significant other health issues, comorbidities for whom surgery is not an option, which historically has been the case. So I think that’s the powerful message from this study.

Rick Bangs:

That is so fascinating, and that’s such a long time coming, and it’s really exciting to hear the results of this study.

Dr. Jason Efstathiou:

Absolutely, Rick. And we’re very, very excited about it. It’s getting a lot of social media buzz as well. And I think, again, two numbers to keep in mind that come also out of this study are one; 30% of the patients that go for radical cystectomy, for example, at at USC or in Toronto would be eligible for trimodality therapy. So it’s a good number. The second one is amongst those that had trimodality therapy, 87% ultimately kept their own bladder, their native bladder. And in this study, whether you had cystectomy or whether you had trimodality therapy, 85% were surviving their bladder cancer long term, which are excellent numbers for this, as we know, very serious disease.

Rick Bangs:

Excellent, really incredible. So tell us a little bit about what’s currently happening with bladder preservation clinical trials in the UK?

Dr. Jason Efstathiou:

Sure. The UK has a long storied history in bladder preservation as well. And some recent studies that have come out of there have shown one shortening the course of radiation. So where in, let’s say, the US standardly maybe around 30 or a little over 30 treatments of radiation are given, the UK has looked at delivering 20 treatments. So giving a little higher doses with each treatment and decreasing the length of the course of 20 treatments. That’s one advance that’s come out of the UK very recently. Another is a trial called the radar trial that was presented at ASCO GU earlier this year that was exploring using what we call adaptive radiation. So, adjusting the plan of the radiation to how the anatomy looks that day when that patient is being treated that day, and trying to escalate the dose of radiation a little further with the advantage of adaptive radiation planning and delivery. So, those are some of the recent trials that have come out of the UK.

Rick Bangs:

Yeah. So just reducing the number of trips to get to your treatment from 30 to 20 as you mentioned, I mean, that’s so important to the patients. Not everybody lives down the street from their clinic. So that’s very meaningful.

Dr. Jason Efstathiou:

Yeah. And that brings us to exciting developments in bladder preservation trials in the US where we’re currently in the midst of designing a trial that would compare 20 to five treatments using advanced forms of adaptive radiation delivery that I was referring to, and bringing much higher doses and much fewer treatments. Five treatments done, not every day, but over the course of a couple of weeks. And that’s very exciting, for exactly the point that you raised, that it may make this treatment accessible or more accessible to more patients who are traveling from far away, having to move away from their home where there’s financial toxicity and burden. And we’re very excited about this developing study, for example. And I know you were asking about other new areas of research and trials.

The other big one that has to be mentioned is immunotherapy. And so in the US we’re running big trials. There’s the SWOG/NRG 1806 trial that is using chemoradiation plus minus immunotherapy. So there’s a randomization to immunotherapy. There’s a lot of exciting potential synergy between specifically radiation and immunotherapy. And so it could well be that the addition of immunotherapy to chemoradiation could lead to even better results. And that’s what these trials are exploring. We’re hopeful and those studies are accruing really well. And so, I guess we’ll see.

Rick Bangs:

I can’t wait. I can’t wait. So, if I’m a patient and I think I’m interested in bladder preservation, maybe I don’t know whether I qualify or not, but what should I know going in if I’ve just been diagnosed, relative to bladder preservation?

Dr. Jason Efstathiou:

Well, I think the key is know your options and what options are applicable to your situation, your type of bladder cancer. And then also know yourself and your own priorities and what kind of treatments make most sense to you. Some patients feel that have the sense of just get it out of me and are very drawn to surgery and I fully support that. Never should a patient feel like their arm is being twisted to one treatment or the other. And going with one’s gut, one has to listen to that. So that’s important to know. One thing we didn’t really discuss as much was quality of life effects and side effects of these treatments. And I think that’s a really important question for a patient to ask. What is life like after a radical cystectomy and a urinary diversion, whether it be a neobladder or an ileal conduit?

Well, the truth is many and most patients adapt very well to that, but there is side effects to all these treatments. Nothing is side effect free. In the world of bladder preserving trimodality therapy, we’ve looked at things like toxicity in terms of bladder and bowel toxicity and what have you. And for the majority of patients, it’s very well tolerated. We’ve also looked at quality of life comparisons between cystectomy and trimodality therapy, and there’s some suggestions, for example, for better sexual function and quality of life with trimodality therapy, a better sense sometimes of informed decision making, often because more than one treatment option is being discussed as an option, and there may be also less concerns about appearance and less life interference from cancer treatment.

So those are some real important quality of life aspects that have been seen in some studies when looking at trimodality therapy versus cystectomy. But the truth is, there are side effects to it all. Most patients do very well with both treatments, but hearing about them and then figuring out what’s the best fit for you and what are you a good candidate for that, that’s what patients should know.

Rick Bangs:

Absolutely. So what if I want bladder preservation, but my doctor says no, and I’m fuzzy on the why, and maybe I think I’m part of this 30% that could get it, or it doesn’t seem to be clear to me whether I am or I’m not. What would you suggest to somebody who’s thinking that they want it, but the answer’s been no?

Dr. Jason Efstathiou:

First of all, sometimes that might be the right answer, depending on the features of the bladder cancer. Sometimes a radical cystectomy and with neoadjuvant chemotherapy is the best way to go. And so, hearing the reasons why and asking why so that you understand the rationale for that, I think is really important. But sometimes all the options aren’t necessarily provided, and so being an informed patient is very powerful. So how can you get informed? Well, one, is to seek out resources. Patient advocate sites. BCAN is an awesome resource. Get on bcan.org and look at the website and look at information. There’s all kinds of support that’s available there. And in discussing it with perhaps other patients that go have gone through treat these treatments may be very, very helpful. Looking at other sites as well. I mean, the American Urologic Association has patient focused websites as well.

The Urology Care Foundation through the AUA, Astro from the radiation oncology. The NCI has often good resources as well. But BCAN stands out as a wonderful patient advocate, support net and group with top-notch information. So I think that’s really important. Seek a second opinion. If you’re not satisfied with the answers or the options provided, seek a second opinion, find a center that is offering different treatments to hear about them. Not every center is, for example, a high surgical volume center. Not every center has trimodality therapy or experience with it. So, sometimes that second opinion or seeking other centers that are accessible to one can be helpful. And then sometimes finding a clinical trial can be a wonderful way to access new and exciting treatments as well. And so asking about clinical trials, looking them up on, for example, the National Cancer Institute, NCI website, all of those things are what I would recommend if, for example, as you said, it’s a patient who wants bladder preservation, the doctor says no. Well find out why they’re saying no, and then look to confirm it and look to these other options as well.

Rick Bangs:

Okay. Excellent. Any final thoughts?

Dr. Jason Efstathiou:

Yeah, no, I think we’ve covered a lot of ground here, Rick. I think we’ve hit all the high points other than I would just say it is really important that we all work together to safeguard the autonomy of patients with bladder cancer. And what does that mean? It means informed decision making by the patient is key. And ideally, that informed decision making is happening in a multidisciplinary environment where the patient is visiting and hearing from and consulting with different specialties, to get a complete picture of the care path and the options available. And so, that would be my final thought, and how we all need to work hand in hand together, providers, patients, support groups, advocacy groups to safeguard the autonomy of patients with bladder cancer.

Rick Bangs:

Yeah, it’s definitely a partnership. Jason, I want to thank you for giving us an understanding of the current state of bladder preservation as a treatment and what patients should know and do. If you would like to connect with Dr. Efstathiou, please send an email to info@bcan.org. That’s bcan.org. If you’d like more information on bladder cancer, please visit the BCAN website, which is www.bcan.org. That’s all the time we have today. If you like this podcast, never miss an episode by clicking on the subscribe button on your favorite podcasting platform. Rating our podcast also helps us reach more people, and please feel free to leave a review as well. Thank you for listening, and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again, Jason.

Dr. Jason Efstathiou:

Thanks, Rick.

Speaker 1:

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.