Exploring Acupuncture's Potential to Mitigate BCG Therapy Side Effects: A Phase I/II Trial - Sarah Psutka

June 15, 2023

Zach Klaassen interviews Sarah Psutka about her Phase I/II trial focusing on using acupuncture to mitigate the toxic effects of Bacillus Calmette-Guerin (BCG) therapy for non-muscle invasive bladder cancer. Psutka explains that while BCG is an essential treatment for high-risk cases, it triggers a severe inflammatory response that can lead to an array of symptoms, including urinary urgency, painful urination, fatigue, and flu-like symptoms. These side effects often become so burdensome that patients quit the therapy, risking cancer recurrence. The trial aims to explore the potential of acupuncture to alleviate these symptoms, given evidence from overactive bladder literature supporting its effectiveness in managing urgency and frequency. The intervention group, who received acupuncture treatments, showed no significant treatment delays, and dropped-outs were primarily due to disease progression. Interestingly, patients reported a highly positive experience with acupuncture, with a large majority expressing satisfaction and willingness to refer others. Early data suggest acupuncture might be mitigating pain and urinary symptoms, warranting further studies.


Sarah Psutka, MD, MSc, Urologic Oncologist, Associate Professor of Urology, Department of Urology, University of Washington, Seattle, WA

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Georgia Cancer Center

Read the Full Video Transcript

Zach Klaassen: Hello, my name is Dr. Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We are live in Chicago at ASCO 2023. I'm delighted to be joined by Dr. Sarah Psutka, who's at the University of Washington. And we're going to discuss some awesome data today that you are presenting at this meeting.

Sarah Psutka: Oh, thanks so much for having me, Zach. I'm really excited to be here.

Zach Klaassen: It's great to have this conversation. So we're talking about your trial Phase I/II trial, looking at acupuncture in patients that are going to get BCG for non-muscle invasive bladder cancer. Just walk us through and remind our audience, some of the toxic effects that BCG can have.

Sarah Psutka: Sure. Well, so as we all know, BCG is the cornerstone of treatment for high risk, non-muscle invasive bladder cancer. The problem is, and this is how I explain it to patients, we are essentially, inciting a massive inflammatory response in the bladder, with the hope that we incite an immune response, and basically, weaponize the immune system to fight the cancer.

Zach Klaassen: Yep.

Sarah Psutka: So basically, we're giving patients the symptoms of a really wretched urinary tract infection.

Zach Klaassen: Yeah, absolutely.

Sarah Psutka: So classically, patients complain of urinary urgency, frequency, and painful urination is probably the worst part of it. The pattern when patients feel those symptoms can be variable. So some patients have symptoms every single time in their 10 out of 10.

Zach Klaassen: Right.

Sarah Psutka: Some patients really tolerate their first couple of cycles pretty well, and then, the toxicity ramps up. Other patients get through induction, and it really hits during maintenance. So it can never really predict who's going to have these kind of really challenging localized bladder symptoms.

And on top of that, they can also have some systemic symptoms.

Zach Klaassen: Right.

Sarah Psutka: The really bad ones, obviously, that we worry about. So symptoms of BCG sepsis, obviously, that's an emergency. That's exceedingly rare now, because we know how to avoid it.

Zach Klaassen: Right.

Sarah Psutka: But I would say, that a lot of patients have fatigue, malaise, lethargy, sometimes fevers and headaches, and sort of flu-like symptoms, myalgias.

Zach Klaassen: Sure.

Sarah Psutka: So BCG is tough. And the problem with it being tough is, one, we don't have great treatments to help, especially with the irritative voiding symptoms.

Zach Klaassen: That's right. Oxybutynin, just doesn't seem to work for it that well, does it?

Sarah Psutka: Not only that, there's randomized controlled trial data that shows that it makes them worse.

Zach Klaassen: Yep.

Sarah Psutka: But that's what we rely on. We rely on anticholinergics.

Zach Klaassen: Sure.

Sarah Psutka: We rely on beta three agonists. Rely on Tylenol, anti-inflammatories. In really bad situations sometimes have to go to steroids for severe cystitis. But there's nothing that really works well. And the trouble is then, of course, is that as the toxicity mounts, the ability for patients to actually tolerate BCG goes down, and then, that becomes problematic. Because while we can usually get folks through their first maybe induction, and a couple of maintenance phases, it's very hard to get people to the end of the SWOG protocol, three years.

Zach Klaassen: It is, yeah. And we were just talking too, I mean, we have patients that would rather quit BCG and risk a cancer recurrence.

Sarah Psutka: Yeah.

Zach Klaassen: The toxic effects get that bad.

Sarah Psutka: Yeah. The impact, and the burden of those symptoms on life. And the other problem is, the amount of time it takes for them to go away.

Zach Klaassen: Right.

Sarah Psutka: I don't know what your experience has been, but I've definitely seen a lot of my patients kind of, the symptoms get better pretty quickly, especially after they get through the first induction and maybe maintenance.

Zach Klaassen: Right.

Sarah Psutka: But if you get out to some of the later maintenance doses, those toxicities persist. And even sometimes past that six, they haven't recovered by the six months when they're coming back for their next round.

Zach Klaassen: Yep.

Sarah Psutka: And that's really disheartening for patients. Because at that point, they're saying they're coming into a round, where they know they're going to get those symptoms again, and they're still not at their baseline.

Zach Klaassen: Yeah. So it brings us to the genesis of your guys' trial, which is exciting. So tell us, how did you guys come up with the hypothesis of acupuncture and BCG? I mean, it really jumped off the computer when I was scrolling through and looking at the program.

Sarah Psutka: Well, it was one of those, so a little bit of right place, right time.

Zach Klaassen: Yeah.

Sarah Psutka: And one of those wonderful moments, where you meet someone who has a really special skillset, and you start talking about things and there's a synergy.

So the story is that, I was at SWOG, and had joined the survivorship committee, and someone said, "Oh, do you know Dr. Heather Greenlee? She's at UW.", who's also on this committee.

Zach Klaassen: Wow.

Sarah Psutka: I had just gotten to UW, so I hadn't had a chance to meet Heather yet. But she's the director of our integrative medicine department.

Zach Klaassen: Excellent.

Sarah Psutka: And she's an incredible researcher and physician. And has a really incredible research program, doing numerous acupuncture trials across different cancers, and also, has an incredible nutrition platform.

So we sat down and had a cup of coffee, and we're talking about different ways that we could leverage complimentary and alternative therapies, to potentially mitigate side effects of GU cancer treatments. And I think at the time, I was struggling with a couple patients who were really having a hard time with their BCG, and I just kind of brought it up.

Zach Klaassen: Right.

Sarah Psutka: And started talking a bit. And she asked me what different drugs we use? And then the fact is, that in the overactive bladder literature, there's actually a fair amount of data that supports the use of acupuncture to manage urgency and frequency, and actually PTENs and inner stim is based on neuromodulation.

Zach Klaassen: It's a great point. I hadn't thought about that.

Sarah Psutka: Yeah.

Zach Klaassen: That's a great point.

Sarah Psutka: So we started talking, and it was just one of those things. There happened to be some pilot funding, there was a deadline coming up, and it was one of those things where we were like, "Why don't we just throw?"

Zach Klaassen: Yeah.

Sarah Psutka: Let's try to put something together.

Zach Klaassen: That's awesome.

Sarah Psutka: So we basically wrote a grant, pretty quickly, and were successful in securing the funding.

Zach Klaassen: That's awesome.

Sarah Psutka: Which was a tremendous opportunity. So the nice thing is, Heather and her team already had a team of research acupuncturists who were really well-trained. They designed an intervention that was meant to mostly manage bladder symptoms, but also, to manage some other regional symptoms. We were using electro acupuncture. And so, we designed a randomized controlled trial, it's a Phase I/II. So mostly focused on feasibility. Because the question is, can we even do this?

Zach Klaassen: Even do it, yeah.

Sarah Psutka: Are patients going to want to do this?

Zach Klaassen: Right. It's hard enough setting up timing for getting people's treatment, let alone mixing in acupuncture, right? So I think feasibility is a great sort of primary outcome.

Sarah Psutka: So can we do that, and can we do it without grinding our clinical workflow to a halt?

Zach Klaassen: Right.

Sarah Psutka: And so, the workflow for the trial was, well, even in our clinics now, I'm sure it's similar for you. Patients come in about an hour before their appointment. They do their urine dip, to make sure they don't have any blood or infection. They wait about an hour, and then they do their BCG treatment. So we just took that hour. During that hour, our trial participants, if they were randomized to the acupuncture arm, so it was a 45% trial, randomized two-to-one, acupuncture to control. It's a weightless control, so there's no sham acupuncture.

Zach Klaassen: Right.

Sarah Psutka: They do their urine sample, and then they're brought into the research room, which we'd set up with an acupuncture bed, warm blankets, low light.

Zach Klaassen: And this is a spot at the infusion center.

Sarah Psutka: Kind of.

Zach Klaassen: Yeah.

Sarah Psutka: And then, the intervention arm patients went through about a 35 to 45 minute intervention. And then, the wait list control patients just got wrapped in warm blankets.

Zach Klaassen: That's nice.

Sarah Psutka: And kind of got to rest.

Zach Klaassen: That's good.

Sarah Psutka: We did quality of life surveys every week. And this happened in the hour before each installation. And then we did a follow-up visit at the end, and looked at quality of life. And so the main questions were really about recruitment, retention, getting people through their BCG, delays in therapy. And then, some sort of implementation workflow, data points for the clinic. Then we also looked at safety, because that's critical.

Zach Klaassen: Sure.

Sarah Psutka: We looked at whether or not giving acupuncture was going to interrupt the receipt of BCG.

Zach Klaassen: Sure.

Sarah Psutka: Because that obviously is, that would be counterproductive.

Zach Klaassen: Yep.

Sarah Psutka: We looked at patient satisfaction with the treatments, and likelihood of referring others for acupuncture, likelihood of getting it again.

Zach Klaassen: Sure.

Sarah Psutka: And then, we did some exploratory work with with PROs, and collected the EORTC, QLQ-C30, and then the NMIBC24. So we had some general quality of life, and then bladder cancer specific.

Zach Klaassen: That's great. So looking at the figure where you described where it sounds like the acupuncture locations were kind of all over the place, right?

Sarah Psutka: Yeah.

Zach Klaassen: How'd you guys decide where you're going to do it?

Sarah Psutka: Well, and that of course, so not an acupuncturist.

Zach Klaassen: Sure.

Sarah Psutka: I've never given acupuncture and have never even received it.

Zach Klaassen: We'll keep our day jobs.

Sarah Psutka: Now, I'm curious about it after actually going through this. But it was developed choosing the accu points that are specifically thought to be relevant for the bladder. And then also, for managing pain and anxiety, and sort of overall wellness. And we actually went through a description of how we chose those points in the protocol paper that we've already published-

Zach Klaassen: Awesome.

Sarah Psutka: ... on the trial.

Zach Klaassen: So tell us about the results.

Sarah Psutka: So the first question, of course, was can we do it?

Zach Klaassen: Yes.

Sarah Psutka: The answer is yes.

Zach Klaassen: Great.

Sarah Psutka: I've run a couple of clinical trials recently.

Zach Klaassen: That's great.

Sarah Psutka: This was the easiest trial to recruit to-

Zach Klaassen: That's awesome.

Sarah Psutka: ... of any of the trials we've ever done. Patients were really excited about it.

Zach Klaassen: Yeah.

Sarah Psutka: And we got it recruited to all 45 patients in the setting of, not only COVID, but also, the BCG shortage-

Zach Klaassen: Right. Two major challenges.

Sarah Psutka: ... in less than a year.

Zach Klaassen: That's awesome.

Sarah Psutka: The next question was, could we retain P patients? And basically, the only people who... There's a sort of heat map looking figure on the poster, but the point of that is to show that the acupuncture didn't cause any delays to treatment.

Zach Klaassen: Right.

Sarah Psutka: The only people who dropped out, were people who dropped out because of disease progression, or sort of recognition of more advanced disease later on during the treatments. There was one patient who was randomized to the control arm who decided that they didn't want to participate. And then otherwise, delays were related to the things we normally see delays for.

Zach Klaassen: Sure.

Sarah Psutka: Things like urinary tract infections and some logistical issues.

Zach Klaassen: Sure.

Sarah Psutka: The next question was safety. There were no grade three or greater adverse events. There were two grade one-

Zach Klaassen: Fair enough.

Sarah Psutka: ... adverse events, bruising and a bit of pain at one of the accu sites.

Zach Klaassen: Right.

Sarah Psutka: Acupoint sites. And then the satisfaction data was really interesting.

Zach Klaassen: Yes, absolutely. That's where the real meat of the results are, other than the safety and feasibility.

Sarah Psutka: 95% of patients were very satisfied, or extremely satisfied with their therapy. 100% had sort of a really positive view of the acupuncture experience. And 75% said that they would refer others to-

Zach Klaassen: That's great.

Sarah Psutka: ... acupuncture while going through BCU. I think we do have data on sort of preconceived notions of acupuncture. We're going to put that in the paper. But overwhelmingly, I think the patient experience was very positive.

Zach Klaassen: Which is key for a trial like this.

Sarah Psutka: And anecdotally, many of these patients are my patients. They would come in for their next cystos, and we'd be talking about maintenance, and they'd say, "When am I going to do my acupuncture?"

Zach Klaassen: That's incredible.

Sarah Psutka: We thankfully have a referral base in Seattle, so we're able to refer them to other acupunctureists, if they want to. But they were very disappointed when we couldn't do it for their maintenance dosing.

And then, the really sort of interesting hypothesis generating data. Obviously, it's a small study, we weren't powered to look at efficacy, but we do have all this quality of life data. And what was, I think, surprising to us was that, when we look at urinary symptoms and pain symptoms. So for pain symptoms, there was a trend, it was not statistically significant, that pain scores decreased more in the acupuncture arm than in the-

Zach Klaassen: That's great.

Sarah Psutka: ... than in the control arm. But the urinary symptoms statistically significantly declined more than the control arm. There does appear to be a signal that we are mitigating symptoms with this intervention. Now there's a lot of work we still have to do, to sort of delve into those PROs, but I think it, there's an enough of a signal that we feel like it warrants a bigger trial.

Zach Klaassen: That was my next question. I think that if you take the fact that the patient experience was good, you've got a strong signal for improvement in symptoms, which is kind of the whole genesis for wanting to do the trial anyways, right?

Sarah Psutka: Yeah.

Zach Klaassen: And the fact that safety, and efficacy, and feasibility were all there. I mean, this seems like a home run Phase III pitch, right?

Sarah Psutka: I hope so.

Zach Klaassen: Yeah.

Sarah Psutka: It was really striking to me then, and I want to emphasize this, that the urinary symptoms, it's not that they stayed the same or they weren't as bad, they actually got better.

Zach Klaassen: Yeah.

Sarah Psutka: Which doesn't happen-

Zach Klaassen: Does not happen.

Sarah Psutka: ... normally on BCG, where the median scores went down.

Zach Klaassen: Yeah.

Sarah Psutka: And there's something that we're going to dive into, and when we write the paper, which is that, the baseline urinary scores in the acupuncture group were actually worse. The acupuncture group was a randomized controlled trial, but the acupuncture intervention group was a little bit older than the control arm. So some of that may be related to age and other sort of baseline urinary symptoms. So we have to explore this.

Zach Klaassen: Yeah.

Sarah Psutka: But I think the signal is really compelling.

Zach Klaassen: And especially like you said, I mean, the fact that you have a group that arguably was a little bit worse than the control and they end up doing better.

Sarah Psutka: Yeah.

Zach Klaassen: Because when I think about this from just a high level view, it would seem that the people that wanted to come to this trial were not desperate, but they were having problems already, right?

Sarah Psutka: There were a lot of people who were worried about getting BCG.

Zach Klaassen: Yeah.

Sarah Psutka: And so, I'm very excited to sort of, there's a couple... I have a lot of questions in my mind because-

Zach Klaassen: Sure.

Sarah Psutka: ... obviously, if you're going to propose something like this to be part of symptom management, not only do we have to make sure it's safe during the study, I think we've been able to demonstrate that.

Zach Klaassen: Yeah.

Sarah Psutka: But the other point that I think is interesting is, you do also need to generate, to understand if there's any impact on cancer control.

Zach Klaassen: Sure.

Sarah Psutka: Now, I don't know that there's necessarily a biological explanation that would suggest that in any way, shape, or form, acupuncture should impair BCG response. But if it is affecting inflammation, it's something we just need to be sure of.

Zach Klaassen: Yeah. No, you're absolutely right.

Sarah Psutka: We're actually tracking all that data as well. So we're going to try to be really careful and thoughtful about this. It was a really interesting study to run. And I think the data is exciting.

Zach Klaassen: Yeah. Absolutely.

Sarah Psutka: So we're enthusiastic about next steps, I think.

Zach Klaassen: That's great. So I think just a couple summary points for our listeners. And I think, as you said, this is very exciting.

Sarah Psutka: Yeah. So basically, acupuncture, one, can be given in a urology clinic in patients who are awaiting their induction BCG dosing. I think the key things that really helped us, just from a workflow standpoint, were one, we had a research room. Obviously, we were doing this on a fairly limited research budget, but we were still able to make it happen. We had a really wonderful group of trained acupuncturists. And the nice thing is, integrative oncology is a really sort of exploding field right now.

Zach Klaassen: Sure. Yeah.

Sarah Psutka: I think a lot of major cancer centers have very robust integrative oncology programs that are developing and/or developed. And it's an amazing opportunity to collaborate with-

Zach Klaassen: Totally.

Sarah Psutka: ... these guys, because they are incredible physicians, and have some really smart ideas about how to manage symptoms. And this is a sidebar.

Zach Klaassen: Yeah.

Sarah Psutka: This is not a take home point necessarily, but there's a lot of other areas where complimentary and alternative medicine can help us in taking care of our patients.

Zach Klaassen: Sure.

Sarah Psutka: Whether it's acupuncture for return of bowel function.

Zach Klaassen: Yeah.

Sarah Psutka: Ileus, postoperative nausea, vomiting.

Zach Klaassen: And I didn't even think about just psychosocial components of stuff. I mean, psycho-oncology, that integration's already there.But this is a whole nother level. But on that same thought process, we got to think outside the block sometimes to help a patient.

Sarah Psutka: Couldn't agree more. And actually, I think the mindfulness based practices, there's something to be said for taking what is a challenging procedure to go through, and having a little bit of sort of TLC at the beginning of it, right?

Zach Klaassen: That's right.

Sarah Psutka: The more wrapping up in warm blankets may not be a-

Zach Klaassen: That's not a bad idea.

Sarah Psutka: That's not a bad idea.

Zach Klaassen: No matter whether it's a trial or not.

Sarah Psutka: Yeah.

Zach Klaassen: Yeah.

Sarah Psutka: So back to take home points. So one, you can do it. Patients really liked it.

Zach Klaassen: Yeah.

Sarah Psutka: We didn't have any issues with a lack of interest, or people saying, "That's not an acceptable idea to me."

Zach Klaassen: Right.

Sarah Psutka: In fact, patients were enthusiastic about joining.

Zach Klaassen: Yeah.

Sarah Psutka: It's safe.

Zach Klaassen: Yeah.

Sarah Psutka: It didn't interfere with the BCG receipt, which is critical.

Zach Klaassen: Which is key. Yep.

Sarah Psutka: And then, there's a pretty compelling efficacy signal that warrants study in a further bigger study.

Zach Klaassen: That's awesome. Thanks so much for joining us. It was a great conversation.

Sarah Psutka: Yeah.

Zach Klaassen: I think our listeners will really enjoy it.

Sarah Psutka: Thanks, Zach. I appreciate it.