Her contributions in the areas of renal malignancies, of urothelial malignancies, of different types of optimization perioperative care are well known, I think, to many of you all. But we're going to talk a little bit about the impact of probably one of the more common patients we see, the patients with recurrent disease, with recurrent low-grade disease, specifically of urothelial carcinoma.
So Sarah, thanks so much for spending some time with us. And look forward to your thoughts and our next steps that hopefully, we can find to help decrease the burden of care for these patients.
Sarah Psutka: Well, Sam, it's always so fun to talk to you and thanks for that very kind introduction.
I feel intermediate-risk, non-muscle-invasive bladder cancer, which is what we're talking about, these recurrent low-grade tumors, it's one of the areas of bladder cancer that for a long time, just didn't get a lot of attention despite the fact that it's so incredibly common.
Sam Chang: Right.
Sarah Psutka: But I do really appreciate through the work of the Bladder Cancer Advocacy Network and IBCG and a number of the organizations that are really working to spotlight the whole spectrum of bladder cancer. This has actually become a high-priority area of the disease, which is exciting because it's probably one of the most impactful.
Sam Chang: Yes.
Sarah Psutka: It's just an impact that is not recognized in the terms that we commonly think about.
Sam Chang: The survival ... I mean, the prevalence and the number of patients impacted in ways ... We often don't measure social cost, patient burdens, burns on the family, but then the everyday cost as well.
Sarah Psutka: The cognitive impact and the work of having low-grade non-muscle-invasive bladder cancer.
I had an opportunity to participate in a couple of focus groups and survey exercises. J&J is running this really nice initiative right now that is really trying to get at understanding the impact of bladder cancer on patients. And really start to characterize what is the lived experience of this disease in the patient's voices, which I so appreciate. And BCAN has done some nice work around this as well.
And some of the data that's coming out of the surveys is fascinating. One striking observation that patients made, that I think a lot of physicians may not just have in their awareness, is that a lot of times when patients are presented with this diagnosis, they're told, "Oh, you have the good cancer." Right? And I think it comes probably from a good place. This is not a lethal disease. This disease is not going to shorten your life.
However, this disease probably has one of the biggest impacts on the quality of life of our patients of any of the cancers that we treat, because low-grade, recurrent non-muscle-invasive bladder cancer is defined by the fact that it keeps coming back. Most patients will have three recurrences in five years. They're going to need to have cystoscopies almost indefinitely. And we'd like to try to de-intensify and stretch those out, but a lot of times if you see a cancer, you're back in three months. And because they keep coming back, then you reset the clock and you have that seesawing, right? Back and forth. You're like, "Oh, I'm disease free." And then-
Sam Chang: Just as you get to that point. Yeah, exactly. Right.
Sarah Psutka: ... "I've got another one and then I got to do it again."
And then we've got to do more ... Then this rinse and repeat paradigm of find a tumor, induction chemo, maintenance chemo, find a tumor. And all of a sudden, you've basically ... I've got patients in my practice who've had this for 17 years. And they've lived ... This is essentially an incredibly burdensome chronic illness they've had for 17 years. So it really minimizes it to say it's a good cancer. And that's very destructive for patients because then it diminishes their experience and the trauma, and that they experience from this diagnosis and the constant recurrences.
Sam Chang: I'm so glad you've mentioned that because I'm very guilty of that in terms of de-emphasizing the danger of this cancer, which I think is important.
Sarah Psutka: Right.
Sam Chang: But you mentioned the words, specifically the adjectives, chronic, burdensome, et cetera, which we don't really do a good job of ...
Sarah Psutka: And I think the emotional distress that comes ... Patients still have ... It's not scan anxiety. I don't think we have a good word for cysto-anxiety, right?
Sam Chang: Right. Right.
Sarah Psutka: But that anticipation of coming in, however frequently they're doing so, then, "Oh gosh, it's going to happen again."
Sam Chang: It's real. Absolutely.
Sarah Psutka: And there's also, I'm sure you feel it too, when you're doing a cysto and you're like, "Looks great, looks great, looks great."
Sam Chang: I'll be the first to admit, for these patients, as we try to determine the best strategies, just as you say, decreasing the cystos, are there other new treatments, et cetera? What kind of strategies do we come up with? I think will be incredibly important. But there's, unquestionably, those patients where I will intentionally overlook and just say, "I think things look great. Let's come back." Because you want to balance that burden of surveillance and treatment with a risk of they start bleeding, they start having symptoms. What do you do?
Sarah Psutka: In the very rare cases it can progress.
Sam Chang: Progress. Exactly.
Sarah Psutka: So I think if you want to quantify the risk, there's the treatment burden, there's the chronic illness factors. There's obviously, the cognitive, financial, societal cost. Just the fact that these are often older patients who have a lot of medical comorbidity and you're saying, "Yeah, we need to put you under a GA again and again and again." And there's risk every time we put somebody under a GA.
Sam Chang: Right. Right.
Sarah Psutka: So what can we do? So this is where this space has gotten so interesting because there's a really big intensification/de-intensification debate. And also, people are starting to think outside the box and say, "Okay, how can we break that TUR chemo maintenance?
Sam Chang: Well, tell me your thoughts. What do you think?
Sarah Psutka: So I think the Italian group has done an amazing job of really legitimizing the idea of active surveillance, which we're talking about, as a strategy for small papillary, low-grade tumors, less than five tumors, less than one centimeter each. You can monitor those. The risk of progression is exceedingly low. And then once one hits that one centimeter mark, you go in and you clean out the bladder and reset the clock on that bladder. They've demonstrated the safety and the oncologic viability of that strategy.
Two, we can do a lot in the office for these patients. We don't have to go to the OR. I frequently am doing now office-based quick biopsy to confirm it, make sure your cytology is negative. And then fulguration in the office, rinse with some gemcitabine. Hopefully, come back next time and everything's clear. And I've saved that patient a whole day in the hospital, their kids taking time off work, the risks of a GA, the pain of surgery.
Sam Chang: Sure.
Sarah Psutka: But then, of course, we now have ablative options like Zusduri, which has an FDA indication as an ablative therapy, intravesical agent that is used with the goal of basically melting away these tumors. Single-arm trial.
Sam Chang: A big, big, big paradigm shift.
Sarah Psutka: Big paradigm shift, but something that we actually need to be thinking about. Can you actually treat these without having to go to the OR? So I think that's exciting. And expensive for sure, but also has, in the single-arm and ENVISION trial, 78% CR rate with pretty good-
Sam Chang: Long-term durability.
Sarah Psutka: ... long-term durability at one year that approached 80%. I mean, that's pretty exciting.
Sam Chang: Right.
Sarah Psutka: There are novel oral agents that are being evaluated in here, the FGFR3 inhibitors. I think that's a really neat idea. Can you give people an oral med and actually ablate their tumors?
Sam Chang: Tumors.
Sarah Psutka: Brilliant. If that works, that will be a game-changer. Very exciting. Let's learn about the toxicity of that. Let's see how that performs. The early trials are in progress.
And then something I've gotten excited about recently is we're thinking about secondary prevention. Can we use other medications to try to prevent the recurrences of tumors? And this is very early days, so I'm just highlighting something that I'm working on right now. Within SWOG, we're looking at pitching a concept that will look at a 5-alpha reductase inhibitor as a preventive agent because there's observational data, and small prospective clinical trial data that suggests that there's a signal if you impact the androgen axis.
Sam Chang: Is it the androgen receptor?
Sarah Psutka: There's a couple of people working around, in both Canada and the United States, on this idea. So there's lots being done, which is really exciting.
And then there's the other side of it where some patients are like, "Yeah, hit me with the kitchen sink. I don't want this to come back. Let's do intravesical gemcitabine induction and let's do a year of maintenance." And so I think this gets at the art of medicine and talking to patients about what are the trade-offs? What are the risks and benefits? What will make you feel best? And then you go from there.
Sam Chang: Yeah. I think balancing all those impactful variables is something that we as urologists need to get better at.
Sarah Psutka: Totally.
Sam Chang: Honestly, we've spent so much, and rightfully so in some aspects, regarding high-risk disease, concern for progression metastasis, which obviously is very, very important. But what you've helped to emphasize and clarify is again, that burden for this large, large group of patients that people will have different areas of stress and impact.
Sarah Psutka: Sure.
Sam Chang: And I think now we're starting to develop appreciation of that and options for that. And as always, I really applaud the steps that you're taking next, Sarah, the research on looking at the impact of the possibility of affecting the androgen axis. I mean, there was some data early on regarding, perhaps there's a role and differentiation in men and women, and all those types of things, but to actually think about it as a secondary preventive.
Sarah Psutka: Well, we'll see. We're pitching the concept right now and trying to build that up. But I think there's a lot of opportunity here, but I think the biggest opportunity for us as a community is to really actually, just understand the impact that this disease has on these patients. It's a huge group of our non-muscle-invasive bladder cancer patients that are in this camp. And I also think it's an opportunity to leverage better risk-stratification tools. So think about like the IBCG risk stratification for intermediate-risk, non-muscle-invasive bladder cancer. The fact that now we can actually start to try to-
Sam Chang: De-escalate.
Sarah Psutka: ... de-escalate for those low-risk patients-
Sam Chang: Escalate.
Sarah Psutka: ... and escalate in the appropriate situation. So provide risk-concordant, risk-adapted care recommendations.
And then I think it's also just relevant to think about how we talk to patients about this disease. And our language matters, as we know so well. I mean, you're so, so thoughtful about how you talk to patients about these cancers.
And trying to get at, with patients when we check in with them, like in the survivorship realm, how is this affecting your life? You mentioned how I get really excited about rehab and getting people fit. So we actually just launched the EMPOWER trial, which is a survivorship timeline in non-muscle-invasive bladder cancer, home-based personalized exercise prescription.
Sam Chang: Oh, I love it.
Sarah Psutka: A randomized controlled trial. So it's funded by Andy Hill Care Foundation and it's a randomized controlled trial for patients in the survivorship portion of non-muscle-invasive bladder cancer care. So these intermediate-risk patients are actually the bucket.
Sam Chang: It's a huge bucket. I mean, these are survivors.
Sarah Psutka: Yeah. Everybody who's on maintenance or just surveillance.
Sam Chang: Right.
Sarah Psutka: And we're trying to see in a 12-week period, can we help make people a little bit more active or not, using a ... The challenge trial was a big exercise trial in colon cancer. We're using their paradigm. So I think there's a lot of ways we can make life better for these patients. I'm trying to figure that out in a couple of realms, but definitely, just having an awareness of how impactful this disease space is is really critical.
Sam Chang: Well, there are many things I wonder about in life, but I have no doubt that you've made huge impact on many, many people's lives. And so we look forward to talking to you always, Sarah, and your efforts for our patients. And all these different urologic malignancies is something that we should all applaud.
Sarah Psutka: Well, thanks. And thanks so much for the time to talk about this. What fun.