Janet Kukreja: Thank you.
Leslie Ballas: Thank you for having us.
Ashish Kamat: So there's a lot of stuff happening here at AUA, and a lot of exciting things. I'm not biased, but I am a little bit. I'm really excited about the IBCG AUA forum, and especially your debate. Because it's a topic that's not only controversial as we saw on social media recently, it was prostate cancer, but still we saw on social media, but it's also very timely. Because with the new advent of new adjuvant therapies that are bladder sparing, with the advent of new trials in bladder cancer with TMT and XRT, this whole notion of who manages the toxicity. Is it the urologist? Is this radiation oncologist? Is it teamwork? Is very timely.
So I know you guys are going to go have a debate tomorrow. It's going to be lively. There's going to be fireworks, but today let's just talk in general. So Janet, your thoughts on the role of radiation therapy, and how the urologist and radiation oncologists fit in.
Janet Kukreja: I live the life of luxury, in the sense that I work very closely with my radiation oncologist. I think for some urologists that are in the community that refer to a community radiation oncologist, the relationship might be very different. I think a lot of times when the patients are on radiation therapy, the radiation oncologist manages the symptoms, and then afterwards they come to the urologist and everything kind of transitions over to us.
Ashish Kamat: Yeah. And I like the way you said that you live a life of luxury. I think I live in Disneyland too, right? Because everything's perfect, and get along so well with our radiation oncologists, oncology colleagues.
But there are many centers, and I hear this from people across the globe, that the radiation oncologists will not even talk to the patient about the toxicity of the treatment, just treat them and then put them on the urologist. So what's your sense of this, in general, and how can we, and when I say we, I mean collectively, all of us together address this.
Leslie Ballas: Yeah. I think that, one, I think it's important to see a radiation oncologist who is used to treating bladder cancer, and therefore has expertise in it, and is also able to have a meaningful informed consent discussion with the patient. I like you to get to have a partner in my urologist, or two partners, the urologist and the medical oncologist.
And so decisions are made obviously in a shared decision-making fashion with the patient, but also as a group in sort of taking care of these patients as a whole. We try to be sure to mention the toxicities or potential side effects from radiation, including the surveillance that's required afterwards. We try to follow our patients every three months for the first year, every six months beyond that. However, we have our urologists, our radiation oncologists and our medical oncologists, are in physically different buildings and so that makes it hard. And I've noticed that that makes even the follow-ups hard for these patients.
And so, oftentimes our patients will choose to follow with the urologist over the radiation oncologist because they're getting cystoscopy at that time. There's a reason for them to be there. So we've actually tried to do a lot more video visits with these patients to try to ease the burden, and also help in continuing that partnership beyond just the treatment.
Ashish Kamat: So let's talk a little bit about the toxicity of radiation therapy, right? Because again, there's several schools of thought and you'll hear some radiation oncology colleagues saying, "Oh, there's no toxicity with radiation therapy." Clearly not true.
On the other hand, we hear some people say, "Oh, radiation toxicity." I mean, radiation's the work of the devil. It kills everybody. Clearly not true, right? There's obviously sense in the middle ground. So when you're talking to a patient with bladder cancer and advising him or her about the toxicity, what are some of the numbers that you use?
Leslie Ballas: So, I think it's really important to distinguish the fact that, on clinical trials where we get this data from to talk about toxicity, those are patients who are well screened and are sort of the ideal patient. In the real world, we treat patients that sort of are outside of the middle of that bell curve, and therefore toxicities are different in the real world.
However, based on what we know and based on clinical experience, we warn them in the acute period that there may be fatigue, there may be more frequent urination, urgency with urination, burning with urination. There may be more frequent and/or loose bowel movements. Usually these acute toxicities go away in the month or two that follow radiation.
We should also be counseling patients about long-term side effects. Those include radiation cystitis, which can be bleeding, scarring, radiation proctitis, similar potential toxicity in the rectum as well as there can be depending, even urethral stricture, and that I always include the potential rate of a non-muscle-invasive bladder cancer and then that would require instillation of BCG, or some form of therapy, into the bladder that has toxicity, especially in a radiated bladder, as well as obviously the risk of muscle-invasive recurrence and then what that side effect profile would look like.
Ashish Kamat: Yeah. And Janet, that brings me to obviously, you're a busy bladder cancer specialist, and you have a lot of patients with non-muscle-invasive disease, muscle-invasive disease, your surgical schedule is really full. And when you're counseling patients on radical cystectomy, for example, for muscle-invasive disease, and they're considering trimodality therapy or let's just say chemo radiation, right, not the classic TMT paradigm. What are you counseling them on as to the pros and cons of the surgical approach versus radiation approach, and the potential for the surgery after radiotherapy?
Janet Kukreja: Yeah. I mean, I think we try to present a very balanced, this is the risks and benefits of radiation. I think when you say, put them on an even playing field, the one thing for me that really changes after radiation is, I don't think that neobladders are really best after radiation. They tend to have really bad leakage that they need another surgery for. It's not a definite no, but we need to understand what this means.
I will also say this, not all radiation is the same. So sometimes you get in there and things are pretty okay, like that patient might have done okay with the neobladder. Sometimes you get in there and all the levators are white and everything is stuck and you're like, "Nothing would ever work here."
So I think it kind of depends on the patient and it's very patient specific. I've had a few patients where I was like, "Well, let's take a look and see what it looks like. If the tissue's healthy, maybe there's a chance." I haven't had one yet where things were really healthy that it's worked out well, but I mean, it does limit some of our diversion options.
Ashish Kamat: Yeah. And Vedang Murthy is a good friend of mine and Tata Memorial does a lot of radiotherapy, and their surgeons are excellent, but every time I've gone there and talked to the multidisciplinary group, they have a very different experience with post-radiation cystectomy. The bladder comes out in piecemeal, it's extremely complicated, patients have a lot of potential problems and Dr. Murthy and the others sort of accept that across the board.
I want to hypothesize a little bit. Do you think that the radiation effects on the tissue are related to patient BMI maybe? Maybe there's some toxicity related to the tissue surrounding based on the patient's genetic profile makeup. Any such thoughts?
Leslie Ballas: In other diseases, we've started to learn quite a bit about toxicity following radiotherapy. There's data in breast cancer, in prostate cancer, and there is certainly a genetic component to it.
There are tests being developed to evaluate potentials for toxicity following radiotherapy in these other disease sites, and we're looking to bring it into the bladder cancer space as well. So I do think that that is a component.
I think that there's other things as well. I think that preexisting comorbid diseases can obviously play a role. Diabetes, for example, possibly BMI. But I do think that while the vast majority of patients, I would agree with Janet, should not have, maybe are not candidates for neobladders. We did do a series of looking at neobladder reconstruction in patients who had prior radiation, both for bladder cancer and for both cervical and prostate cancer. And there were, in the properly selected patients, the possibility of doing a neobladder.
Ashish Kamat: So we've had a nice general talk now. Now I'm going to put you guys on the spot and say, "Okay, we're debating what you're debating." So radiation toxicity, who should manage it and why? Janet?
Janet Kukreja: I think it depends on what the toxicity is. So there are some toxicities that I think radiation oncologists, especially many years down the line, don't want to manage. So like severe radiation cystitis, for example, I think is probably best managed by a urologist.
The acute toxicities I think are really better managed by the radiation oncologist, like the proctitis, the lower urinary tract side effects. I think those are more in their domain, but the chronic toxicity is almost always the urologist that's involved, just because of the nature. We're taking them to the operating room, we're fulgurating, we're putting in formalin and we're sending them hyperbaric. And sometimes they need diversion, NF tubes. We're running that whole show.
Ashish Kamat: Leslie?
Leslie Ballas: I agree. I mean, I think that radiation oncologists should manage all acute side effects. Everything while they're on radiation treatment, and built into the radiation oncology schedule is a weekly visit with your doctor.
But the minute that we send someone back to the urologist or the urologist deems that it's necessary to look inside their bladder is the moment when I think that urologists are going to take over the lead, mostly because they're looking in, they're physically there as Janet was saying.
But I do want to say that the data would show from large trials that the rate of cystectomy for toxicity due to radiation is in the one to 2% range. Again, as we discuss, that's trial data, but that is what is reported in the literature. We've all seen our fair share of patients that have radiation induced toxicity, but just to make it clear to our viewers that it's not, as you mentioned earlier, the devil.
Ashish Kamat: Right.
Janet Kukreja: I mean, I also kind of feel like there are some radiation oncologists that maybe do their plans in a way that the bladder gets more radiation than some others do. And we tend to see some of these more long-term side effects from different centers that are not necessarily like our center, where I think they're doing the plan and the dosing a little bit differently.
Leslie Ballas: I think actually that's a really great point. So up until the SWOG NRG 1806, there wasn't really great radiation constraints or doses that were known, that were put on bladder and normal surrounding structures using intensity modulated radiation therapy, because for a very long time radiation was given with sort of a wide open field from front, back, and sides, and what we would call a four field box. And we're still, I mean, I'm sure you guys are still seeing the effects of that therapy now. And so, there is a definite lag time between the improvement in radiation technique.
Ashish Kamat: Yeah, I think those are great points, because if we look at the literature and again, the trial's different, but the real world experience radiation toxicity leading to cystectomy rates are as high as 23% in some reports. And that clearly, to me, I don't see that in our practice. I don't see that when radiotherapy is done properly, neither do the UK folks, or Mass General, or most of us don't see that.
So I think it's a reflection on the fact, and correct me if I'm wrong, but I heard from my radiation oncology colleagues that, even today in the residency program for rad-onc, there isn't a true focus on bladder radiation. Is that...
Leslie Ballas: Yeah. So residents rotate through GU services, and it really depends on the institution and how that institution's sort of practice patterns are. And so many institutions don't use bladder preservation all that often, and then residents won't see it and they won't get some of this education, and certainly then won't get the education how to manage these patients.
Ashish Kamat: Right. And I think again, we're all talking the same thing. We all believe that we are in it for the patient, right? So the patient is having a toxicity that I can manage or you can manage or you can manage. We would manage it the way we want to.
But I think one of the things is to address the whole toxicity issues, we need to educate our counterparts in the community, that may be doing that one or two bladder planning TMTs in a year, they should probably get a little bit more educated on how to do that. The same way we wouldn't expect someone to do one radical cystectomy a year and do it well, right? I mean, it is a technique and it is very technically demanding. This is-
Janet Kukreja: I think that's where it's a little different though. So radiation oncologists, they don't necessarily refer to each other. So we have very laid out referral patterns, where it's a pretty clear cut that like these people over here are not going to do cystectomies. There's like a handful of people in the state that do a cystectomy, right?
Radiation oncology is not the same way, right? They're not referring to the high-volume bladder trimodal centers, right? They are doing the one to two cases.
Leslie Ballas: I think that that's a very accurate statement, and I think that some of that comes from the fact that, and not necessarily the two of you, but people say, "Oh, well, there's radiation oncology in your community. You can get it there." It's easier, it's more convenient. I live in Los Angeles where traffic determines where everyone goes and I can tell you I hear that all the time. "Oh, well, there's radiation in my neighborhood. Why should I drive here?"
And I think that the answer is not only expertise, but it also allows for exactly as we're talking about here, sort of many physicians under the same roof taking care of the same patient. And so, I think that's an important thing for patients to consider.
Ashish Kamat: Yeah. I mean, I tell patients all the time that ask me that very question. I think I say no, well planned radiotherapy for the bladder, anything, but especially for the bladder, is just as technology and person dependent as good surgery is, right? So you don't want to just go anywhere.
This has been a great conversation. I'm obviously looking forward to some zingers tomorrow at the debate, but in closing for our audience that is truly global and taking care of patients in different parts of the world, closing message from each of you. Janet.
Janet Kukreja: Yeah. I mean, I would just say get to know the people in your community that are doing these things, and really try to partner. Don't try to take it all on yourself, whether you're a radiation oncologist or a urologist, like partnership is probably best.
And sometimes if things are not going well, bounce it off each other. So sometimes I have patients that are getting radiation for prostate cancer, bladder cancer, whatever, and the radiation oncologist is like, "I think there's something wrong. Can you look and see if there's a good stricture?" And yeah, happy to do that. So it's all about partnership, in my perspective.
Ashish Kamat: Great. Leslie?
Leslie Ballas: I agree. I think that the teamwork is essential and I would be remiss not to end this by saying that we are talking about radiation oncology toxicities, and of course there are toxicities, but when you look at quality of life questionnaires done retrospectively on patients who have TMT, they are very happy. They do better than, many of them from randomized trials do better than when they presented with their bladder cancer. And so, we are talking about, hopefully a minority of patients, and it is a good option.
Ashish Kamat: Great. Thank you so much. It was a pleasure.
Janet Kukreja: Thank you.
Leslie Ballas: Thank you.