Revolutionizing Radiation Therapy for Bladder Cancer

December 3, 2024

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Transcript

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. Beacon 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 Dr. Kent Mouw. Dr. Mouw is an Associate Professor of Radiation Oncology at Harvard Medical School and a radiation oncologist at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital. Dr. Mouw provides radiation oncology care for patients with tumors of the bladder and other genital urinary organs. Dr. Oversees an NIH funded basic and translational research laboratory that investigates the role of DNA repair and cell cycle pathway alterations in bladder cancer and other tumor types. Dr. Mouw. Welcome.

Dr. Kent Mouw:

Thanks Rick. It’s great to be here.

Rick Bangs:

I thought we’d start with the basics here. So what exactly is radiation and how does it work as a treatment for both cancer in general and bladder cancer in particular?

Dr. Kent Mouw:

Sure. Yeah. So radiation as it’s used to treat cancer, most commonly are just high dose X-rays, and so the same type of radiation that you would be getting with a chest X-ray or a CT scan is used to treat cancer, but it’s just a lot higher energy and a lot more focused. And the reason that radiation works, in this context, to kill tumors is because tumors, as they’re rapidly dividing, tend to be more sensitive to radiation induced damage to the tumor cell DNA. And tumors are less able to repair this damage than normal cells, which provides a therapeutic window for us to treat bladder cancer and other tumor types with the intent of completely getting rid of the tumor but not permanently damaging the normal organs, which in the case for bladder cancer includes things like the bladder itself as well as organs around the bladder, like the rectum, the bowel, and the bones.

Rick Bangs:

Excellent. All right, so one question. I know a lot of patients ask this and you hear it probably all the time, but I think some patients are concerned they’re going to be radioactive after they get a radiation treatment. So can you confirm that they will not be radioactive?

Dr. Kent Mouw:

Sure, yeah. So there are radioactive sources that are used for treatment of some kinds of cancer. However, bladder cancer is universally treated without, at least in the U.S., without treatments that include radioactivity and so bladder cancer, patients who receive radiation as part of their treatment will not be radioactive for, during, or after the treatments.

Rick Bangs:

So I don’t have to stay away from my loved ones after I’ve gotten my bladder cancer radiation treatment.

Dr. Kent Mouw:

That’s correct.

Rick Bangs:

Okay, excellent, excellent. And then can you comment a little bit on… Radiation today is a different animal than it would’ve been in 50s, 60s, 70s, 80s. So can you comment a little bit about some of the progress that has been made?

Dr. Kent Mouw:

Yeah, yeah, that’s absolutely correct. So there’s been a pretty dramatic evolution in the way that the radiation is delivered, particularly in the types of imaging that we’re able to use to identify, locate, and track tumors as well as our ability to really sculpt the radiation dose to maximize tumor in the target area, which is the bladder tumor, and minimize radiation dose to the adjacent normal tissues. And because of this improvement in targeting and dose delivery, in general, I would say, and this is the case for radiation oncology treatments generally and in bladder cancer as well, is that we’re able to deliver a curative dose in fewer treatments because we’re able to deliver a higher dose in each treatment because the treatments themselves are more specifically delivered to the tumor with sparing of the normal tissues. And so whereas as recently as 10 or 15 years ago, bladder cancer patients were often being treated with up to 30 or more daily outpatient radiation treatments.

That number continues to go down. Right now a lot of my patients that I treat have four weeks of daily radiation treatment Monday through Friday and there are certainly efforts, clinical trials being designed and run today that are experimenting whether even a lower number of treatments as low as a week or two of treatments can be just as effective in controlling and curing cancer and provide, obviously, the patients with the benefit of fewer treatments to the department.

Rick Bangs:

That would be great because then you don’t have to make as many visits to the clinic, right? So that would be great.

Dr. Kent Mouw:

Yep, absolutely.

Rick Bangs:

And I like the term sculpt your radiation because it has a nice visual associated with it about the targeting. I like that. That’s great.

Dr. Kent Mouw:

And I think that’s one of… Like I said, one of the areas where I think the majority of the progress has been made is really our ability to visualize the tumors and then to design radiation plans that are specific to a patient’s anatomy and to that patient’s tumor size and location and really get as much dose in the target as possible and really have the dose fall off outside the tumor be very steep such that the adjacent organs around the tumor and the bladder get much, much lower dose.

Rick Bangs:

Yeah, that makes perfect sense to me. All right, so are there different types of radiation, and if there are, are those types typically available everywhere or can I only get them in metropolitan areas and academic institutions? What’s the range here?

Dr. Kent Mouw:

Yeah, that’s a great question. And so the vast majority of radiation that’s delivered in the U.S. is the type that I just described. So high dose X-rays focused on the tumor. There are a small number of centers around the U.S. and around the world that use so-called particle radiation. So people may have heard of proton radiation.

Rick Bangs:

Uh-huh.

Dr. Kent Mouw:

In other countries there are things like carbon ion radiation. Those are different types of radiation but delivered with the same intent to treat and cure patients with bladder cancer or with cancer generally. However, in bladder cancer specifically, there isn’t really a demonstrated role for those particle radiations like proton therapy and so the vast majority of bladder cancer patients getting treated today in the U.S. are getting treated with the, so-called conventional high dose sculpted radiation that I described.

Rick Bangs:

So I shouldn’t feel let down that I didn’t get the proton beam therapy in bladder cancer because we don’t have any evidence that it is better as yet.

Dr. Kent Mouw:

Correct. So there’s no evidence from clinical trials that proton radiation, or any other type of sort of non-standard radiation, provides better outcomes than the conventional radiation that can be delivered in many different types of settings across the country.

Rick Bangs:

Okay. All right. Now let’s talk about who gets radiation treatment for bladder cancer and is it available to patients who might not otherwise be able to get chemo or surgery?

Dr. Kent Mouw:

Yeah, great questions. So I think that there are lots of different settings in which radiation can be discussed for treatments of muscle invasive bladder cancer. And to get back a little bit to the last question you asked about the types of radiation that are out there. And I think as important as I, as radiation oncologist, believe that the equipment is, I think much more important than that is the team. The radiation oncologist is part of a multidisciplinary team that cares for bladder cancer at many centers and so a patient’s ability or a patient’s potential to get radiation is dependent on meeting a radiation oncologist and that typically takes place at our center and in other centers in a multidisciplinary team setting. And whether that means meeting different providers on the same day or spread out over time, I really think that that’s a great management paradigm for patients with newly diagnosed muscle invasive bladder cancer is to meet the types of doctors that could potentially be able to offer curative treatment.

That includes a surgeon, a urologist, a medical oncologist which can give chemo or immunotherapy, and then a radiation oncologist. And together, I think that expert group of multidisciplinary providers is best suited to help provide recommendations for patients with specifically muscle invasive bladder cancer on what their treatment options are and what their outcomes could look like. And so to sort of move to who should get radiation and who shouldn’t, and again, that’s a very sort of nuanced multidisciplinary decision. I tell my patients that we provide recommendations, but ultimately the patients are the captain of the ship and they get to make the decision that feels best for them. Radiation is unique in that it can be delivered to a wide variety of different types of patients. And so for patients, for instance, bladder cancer increases with age, the bladder cancer incidence does, and so I treat a lot of older patients who may not be willing or able to undergo a big surgery like a cystectomy and so radiation is often a good choice for those patients.

It also can be a good choice for patients who are good surgical candidates. And to speak to the chemo thing, the good news with chemotherapy is that there’s good evidence that adding chemotherapy to radiation improves outcomes compared to radiation alone but there’s evidence for several types of chemotherapy in that setting. And so based again on a patient’s health bladder function, patient preference, there are actually a couple of different options for the chemotherapy that can be delivered and if a patient’s not eligible for any of them, then oftentimes radiation alone is still an option.

Rick Bangs:

Good. All right, so now let’s talk a little bit about who should not get radiation.

Dr. Kent Mouw:

And so again, in the context of this multidisciplinary discussion with a urologist and a medical oncologist, there are certain factors that I believe make patients better or potentially less good candidates for radiation-based treatment for their muscle invasive bladder cancer. There are some things that are relatively uncommon but are, in my view, reasonably strict contraindications to radiation. That’s for patients, for instance, who may have had prior radiation to that part of their body, whether it be for prostate cancer or cervical cancer or something like that. It’s not an absolute contraindication, but often if possible, radiation for the bladder cancer is likely may not be the first choice in that context. Also, there are some patients with inflammatory bowel diseases like Crohn’s disease or ulcerative colitis. And again, not an absolute contraindication, but often for those patients, the discussion will largely focus on non-radiation-based treatment options. Those are rare but not exceedingly rare things that come up in clinic.

And then there are other, I would say, more tumor-related factors that help guide our recommendations between radiation-based approach and the other curative approach today, which is radical cystectomy, the surgery. And there are things like tumor size, tumor location, hydronephrosis, which is swelling of the kidneys caused by tumor, the presence of CIS or carcinoma in situ. All of these are factors that are discussed in this multidisciplinary setting and we know that there are some features that can be associated with better or worse outcomes independent of therapy so independent of whether the patient chooses chemotherapy and radiation or whether the patient chooses surgery and so it can be a nuanced discussion. However, there are patients with very large tumors, patients whose tumors are causing swelling in their kidneys, patients with extensive amounts of carcinoma in situ two in their bladders. Those are typically patients for whom we think radiation-based treatment may be less effective than we want it to be.

Rick Bangs:

Wow. And CIS or the carcinoma in situ, that’s the flat one, right? That’s the one that it doesn’t look like the broccoli stalk, it’s flat on the surface of the bladder.

Dr. Kent Mouw:

Yeah. Yep, that’s right.

Rick Bangs:

Okay. All right. So let’s suppose you recommended, and I agreed, that I was going to get radiation. I’d like to know a little bit about the typical schedule, and I think what I heard you say is every day for four weeks, which would mean I’m going to get 20 treatments, but I want to hear what the actual answer is.

Dr. Kent Mouw:

Yeah, no, that’s a pretty good synopsis. I think obviously the recommendations can vary from patient to patient, but I would say a common scenario in my practice is that I will meet a patient in the multidisciplinary setting through a conversation with other providers and the patient. We come to the decision to move forward with radiation-based treatment and I will work closely with the urologist to ensure that the patient has had a maximal safe transurethral resection. So patients may be familiar, that’s the procedure, this procedure to scrape and biopsy the tumor, but it’s important leading into radiation-based treatment that the surgeon remove as much of a visible tumor as is possible and so I’ll communicate closely with my surgical colleagues to make sure that that is the case.

And then in terms of the radiation itself, patients undergo what we call a radiation mapping appointment, and that’s when it’s a one-time appointment in the radiation oncology department, patients will have a CT, sometimes also an MRI, and that is the imaging information that we, as the radiation team, use to plan the radiation that’s specific to the patient’s anatomy in the patient’s case. And so that’s a one-time appointment and then the daily radiation treatments start usually about a week or two after that mapping appointment and that’s a time period when we’re doing our radiation planning and QA.

Rick Bangs:

Okay.

Dr. Kent Mouw:

And then when the daily radiation treatments start, a common course, as you suggested, is about four weeks. So every business day for four weeks the patient will come in as an outpatient. I tell folks that they’re in the department each day for not that long, often less than an hour.

Rick Bangs:

Oh.

Dr. Kent Mouw:

They check in. When it’s their turn, they go into the radiation treatment room, which is just a wide open room with a table in the middle. The patient lays flat on their back on the table, the radiation machine rotates around them, but it doesn’t touch them usually. They’re on the table for 10 or 15 minutes and their only job really is to lay still. Most of that time that they’re on the table is actually spent taking images to make sure they’re lined up in exactly the same position each day and we use imaging like X-rays and also CT scans so that we can get really clear pictures of the bladder on a day-to-day basis to make sure that the bladder fullness, the rectum shape, all of that looks reproducible from day-to-day.

And then once we’re convinced that’s the case, then the radiation itself is just delivered in a minute or two. The radiation, like a chest-ray X, can’t see it, hear it, can’t feel, it doesn’t burn, and when the treatment’s been delivered, the patient gets off the table, goes on with the rest of their day, and then comes back the next day and just repeats that each business day for about four weeks. And then I mentioned earlier that most patients who are eligible would be recommended to get chemotherapy during the weeks of radiation. And so if they’re getting radiation five days a week, typically one or maybe two days each week, the visit in the center is a bit longer because in addition to getting the radiation, they’re also getting a chemotherapy infusion and there’s good evidence to suggest that the addition to that chemotherapy helps the radiation work better and improves the outcomes.

Rick Bangs:

Oh, okay. Excellent. All right, so I think I heard you say that it wasn’t going to burn, and so I’m guessing, therefore, it’s not going to be painful as I’m getting the radiation and whether it’s the first dose or the last dose, is that right?

Dr. Kent Mouw:

Yeah. So there’s no particular sensation as you’re receiving the radiation itself. The side effects of radiation tend to sort of build up over the weeks of daily treatment and then get better in the weeks after the treatments are over.

Rick Bangs:

Okay.

Dr. Kent Mouw:

And so I tell folks to sort of expect three things. One is some fatigue, and I would say for most patients, this is mild to moderate. It again, tends to peak near the end of radiation and then get better in the weeks after the treatments are over. But I generally tell folks that they should be able to do mostly what they’re used to doing each day. So some patients who work actually continue to work during the radiation treatments, others who live by themselves drive, that sort of thing. All of those things patients can typically continue to do if they were doing them before they started the radiation.

Rick Bangs:

Yeah.

Dr. Kent Mouw:

The second thing I tell everybody to expect is some increased urinary urgency and frequency. And this is because in addition to treating the tumor in the bladder, the radiation can also irritate the normal bladder, and that can manifest as patients feeling like they have to urinate more urgently or more frequently.

Rick Bangs:

Okay.

Dr. Kent Mouw:

That again, tends to build up gradually during the weeks of radiation and then go away gradually in the weeks after the treatments are over. And then the third thing I tell everybody to expect is some bowel irregularity. The bowels sort of surround the bladder on several sides and those can become a little bit disrupted. That can be contributed as well if patients are getting chemotherapy. And what I tell folks to expect is just to be less regular. And so maybe to fluctuate a bit more than you used to between constipation and diarrhea. If medicines are needed, it’s typically over-the-counter things. And again, that tends to get better in the weeks after the treatments are over. And thankfully, the longer lasting or the more serious side effects of radiation are far less common. But those would be things like permanent bowel or bladder changes or damage to an organ that would require a separate procedure to fix. Those are thankfully really rare using the techniques that we now use for localization and targeting.

Rick Bangs:

And what about sexual function? Is that going to be impacted either in the short run or the long run?

Dr. Kent Mouw:

It can be. And so patients who are… There’s no specific contraindications from a radiation perspective, the chemotherapy can impact, there will certainly be specific recommendations around intercourse and childbearing relative to the chemotherapy and I would certainly defer to my medical oncology colleagues for that. Radiation over the long term can have impacts for erectile function in men or vaginal symptoms in women. And so for many men and for many men and women, bladder cancer patients, we will have a discussion up front, perhaps make a referral. A urologist often is involved in the discussion around erectile preservation for men. We have a pelvic floor physical therapist who works with our team for help with things like vaginal dilators and things like this to maintain as much of the normal vaginal and pelvic function in the post-treatment period. And really as part of the multidisciplinary team, we try to include those providers to make sure that patients are able to maintain as much function as possible in the post-treatment period.

Rick Bangs:

Okay. All right. So I have two more questions. Because we hear about this, when people have had treatments for one cancer, they might get another cancer. So are there any risks around getting, I think you call them a secondary cancer as a result of a radiation therapy?

Dr. Kent Mouw:

So every time that we use radiation to treat cancer, the consent form will say that there’s a risk of, as you describe it, a second malignancy or radiation induced cancer.

Rick Bangs:

Yeah.

Dr. Kent Mouw:

Thankfully, those are tumors that typically take many years to manifest and, thankfully, the rates are very low and, thankfully, getting lower because of our ability to more precisely target tumors.

Rick Bangs:

The skull thing.

Dr. Kent Mouw:

I would say, as a radiation oncology community, we think about second cancers a lot for say pediatric patients with Hodgkin’s lymphoma who are young and having large parts of their body radiated. Thankfully, the absolute increased risk of secondary cancers, for instance, cancers in the rectum of bladder cancer patients are very low. And again, because the average bladder cancer patient is older, although there are clearly are subsets of bladder cancer, patients who are in their thirties, forties, fifties as well, I think it ends up becoming less of a part of the calculus. However, strictly speaking, there is a slight increased risk and I discuss that in detail with all my patients. It’s on the consent forms, but, thankfully, very, very rare using the techniques that we now use.

Rick Bangs:

Excellent. The skull thing and all-

Dr. Kent Mouw:

Yeah, that’s right.

Rick Bangs:

… seems to be helping us in our favor. Okay. And what about… Because I’ve heard this over the years, what about my ability to get a neobladder? So if I’ve had bladder preservation and it included radiation, what happens if I need to have my bladder removed for whatever reason, the cancer or whatever? What does that mean relative to my getting a neobladder?

Dr. Kent Mouw:

Yeah, so certainly we know that, unfortunately, despite our best efforts, there are a subset of patients who after having radiation for their muscle invasive bladder cancer will develop a recurrence that necessitates a recommendation for cystectomy.

Rick Bangs:

Yeah.

Dr. Kent Mouw:

And I would say that traditionally it has been felt that the ability to have a neobladder reconstruction after having received bladder cancer radiation is that likelihood is much lower. And there are many urologists out there with lots of experience and I would say that having a discussion, frank discussion with your urologist before radiation and then after radiation, if necessary, about a potential to have a neobladder would be worthwhile for any patient. But certainly I would say that it would be a complicating factor in terms of neobladder having had prior radiation.

Rick Bangs:

Yeah, I think it would also make sense to potentially get a second opinion if you’re in that situation because some surgeons would feel more comfortable than others using a neobladder. So there’s some dependency on the surgeon, I think.

Dr. Kent Mouw:

Yep, I absolutely agree.

Rick Bangs:

All right. So research is one of the things you do and in this space particularly, so I was interested in some of the questions that you feel our audience might find interesting in this area.

Dr. Kent Mouw:

Sure. Yeah. So we’ve been talking a little bit of detail about radiation here and so I’ll just highlight a couple of the most interesting radiation-specific research directions that I think are out there. And so as I alluded to, our ability to target tumors continues to improve. With that, like I said, I think from a very patient-centric perspective, we have the potential with our next generation of bladder cancer clinical trials to define new paradigms that involved fewer treatments for each patient while maintaining very high cure rates and so I’m really excited about that. There are approaches such as things called adaptive radiation, which means that the radiation plan itself can be edited even on a day-to-day basis based on very small changes in the patient’s anatomy, again, allowing us to safely deliver higher doses of radiation per treatment and so I think that that is one area I’m particularly excited about.

We talked a little bit about combining chemotherapy with radiation. I think that advances in chemotherapy and even more broadly in other systemic therapy options, so things like immunotherapy or antibody drug conjugates like enfortumab vedotin are really exciting advances that have taken place in our field over the past three to five or now even longer number of years and I think understanding how those therapies integrate with radiation will continue to be a very intense topic of study and I’d like to think that we are just scratching the surface in terms of understanding how we can combine different treatment modalities to provide the most synergy in terms of antitumor activity while still providing safe curative intent options for patients.

And then finally, I think one additional sort of thing that I’m particularly interested in is the idea that we use tumor and patient specific biomarkers to really inform our treatment decisions and allow us to provide personalized treatment approaches for each patient based on their specific factor. And so there are certainly things like tumor DNA sequencing to find out the tumor mutations that could play a role here. There are things like circulating biomarkers, so CT DNA, measuring tumor DNA from the bloodstream or from urine samples are being investigated as ways to understand where the disease is and how to best target it where it is.

And so I think I’m an optimist at baseline, but I think that the next several years are shaping up to be really exciting. And I think that if we were to do this again in a few years, I would be telling you that the standard of care may be different then as it is now and all of that is with the goal of continuing to improve response and cure rates all while maintaining and improving the patient experience in terms of the cancer treatment journey itself, and then in the post-treatment period.

Rick Bangs:

Okay. I’m going to be looking forward to booking that in a few years.

Dr. Kent Mouw:

Yeah, you can hold me to it.

Rick Bangs:

I am. I am. I mean, it’s such an exciting field, so thank you. All right, any final thoughts you want to share?

Dr. Kent Mouw:

No, I thank your listeners a lot further their interest in this topic. I’m always, as a radiation oncologist, always happy to talk about radiation and bladder cancer. I think that, like I said, the field is ripe for advances and I’m excited to be a part of it.

Rick Bangs:

Excellent. Excellent. So Dr. Mouw, I want to thank you for providing us with an understanding of the current state of radiation and bladder cancer and the exciting possibilities that are being explored.

Dr. Kent Mouw:

My pleasure. Thanks again.

Rick Bangs:

If you’d like more information on bladder cancer, please visit the BCAN website, www.bcan.org. In case people wanted to get in touch with you, could you share an email address or a Twitter handle so that they can do so?

Dr. Kent Mouw:

Yeah, absolutely. My Twitter handle is @mouwlab, so it’s @M-O-U-W-L-A-B. That’s a pretty reliable way to get in touch with me.

Rick Bangs:

Excellent. Just a reminder, if you’d 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. Mouw.

Dr. Kent Mouw:

Thanks.

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.