Discussing findings from a phase 1/2 study, Sarah P. Psutka MD, looks at the use of acupuncture for patients with non muscle-invasive bladder cancer prior to induction of their BCG treatment.
The use of acupuncture before induction of intravesical Bacillus Calmette-Guerin (BCG) treatment is safe and feasible for patients with non muscle-invasive bladder cancer, according to data presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting.1
These data were from a phase 1/2 trial (NCT04496219) that looked at 43 patients randomized 2:1 to either acupuncture prior to treatment or no acupuncture. According to Sarah P. Psutka MD, who presented the data at the ASCO meeting, the majority of patients given acupuncture would recommend it for other patients on this cancer treatment. Further, no adverse events (AEs) from the acupuncture were observed but BCG-attributed AEs were. These included pain in 28% of patients given acupuncture compared with 43% in the control arm (P = 0.34) and urinary symptoms were seen in 62% versus 79%, respectively (P = 0.31).
While the study was not powered to decide efficacy outcomes, according to Psutka, associate professor of urology at the University of Washington Medical Center, physician at Fred Hutchinson Cancer Center, efficacy was a part of secondary outcomes showing a change in quality of life for patients given acupuncture. Over the study period, median urinary symptoms showed a greater improvement for patients given acupuncture compared with those on the control arm at a score of 9.5 (IQR, 0.0-19.0) versus 0.0, (IQR, -14.3-7.1), respectively (P = 0.02). Moreover, there was a trend toward improvement in overall pain scores for patients in the acupuncture arm.
In an interview with Targeted OncologyTM, Psutka discussed these findings and why the use of acupuncture is important for these patients undergoing BCG treatment for their non muscle-invasive bladder cancer.
Targeted OncologyTM: What was the rationale that led to this trial?
PSUTKA: BCG, which is the live attenuated tuberculosis vaccine, is the cornerstone of treatment for [patients with] high-risk non muscle invasive bladder cancer. It's a medication that's placed in the bladder, it dwells for an hour or 2, then patients voided out and the goal is that it creates, essentially, an immune response that is geared towards reducing the risk of recurrence and progression of non muscle-invasive bladder cancer. We've used it for decades, it has a proven track record in reducing the recurrence and progression risk, which is substantial, especially with [patients with] high-risk non muscle-invasive bladder cancer, but it's incredibly hard on patients. It increases frequency urgency, painful urination, or dysuria, there's also an increased risk of things like infection, and the problem with those toxicities is that they're challenging to manage.
They reduce quality of life as patients are going through the through the therapy, and they can interfere with the patient's ability to receive therapy. If the cystitis becomes so severe that patients can't tolerate the therapy, we sometimes have to dose reduce and we have to delay doses. Oftentimes, during the maintenance series, where patients are coming in for these 3-week booster rounds, at set intervals, the AEs can be so severe that they can actually preclude patients from being able to tolerate maintenance.
This is important because we know that the ability to receive ongoing maintenance dosing, especially if we get out to ideally at least 1 year but preferably 3-years based on the original SWOG data, that's critical to maximizing efficacy. So, the trial was geared to sort of leverage integrative medicine techniques, complementary and alternative therapies to mitigate AEs and try to reduce the toxicity that patients experience as they're going through BCG therapy, with the goal of improving the ability of patients to receive BCG as indicated, but potentially, improve quality of life on therapy and/or reduce the decrements in quality of life that patients experience.
Please explain the design of the study.
[This was] a randomized controlled study. It's a phase 1/2 trial, which means it was geared to demonstrate feasibility and safety. We did look at some secondary outcomes that were geared towards efficacy, [as well]. We wanted to understand, could we even recruit to an acupuncture trial in patients with high-risk non muscle-invasive bladder cancer undergoing induction BCG? Could we get patients through the protocol safely? So, we needed to understand whether they're going to be any safety signals from the acupuncture itself, but also, if it was going to interfere with the patient's ability to receive BCG, because that is an outcome that we want to avoid. Secondly, we looked at patient satisfaction with the intervention in the acupuncture arm, and then finally, we did collect patient reported outcomes throughout the trial, both...general cancer related quality of life and then bladder cancer specific quality of life.
How did you administer acupuncture in the trial?
The target sample we wanted to recruit was 45 patients, of course this happened in the middle of COVID, but we were remarkably successful and recruited 45 patients. Ultimately, we randomized the 45 patients and in total 43 patients made it through the trial. Several patients dropped out at certain specific time points, not due to problems with the intervention, but due to progression of disease and in one case because a patient was randomized to our control arm and did not want to wish to participate.... Importantly, there were no safety AEs, so there were 2 grade 1 AEs but no grade 3 or greater AEs related to the acupuncture itself. When we looked at whether the acupuncture interfered with the patient's ability to receive BCG the acupuncture did not interfere with the patient's ability to receive BCG or was associated with any delays to receipt of care.
In a normal practice, the workflow is such that the patients come in and have a urine sample obtained to make sure there's no blood or infection, which that means that it's safe to have the BCG for that day. Then, they wait about an hour while that sample is processed for their appointment. So, during that hour was when we brought the patients back into a study room and patients who were randomized to the acupuncture arm would undergo a 35-to-45-minute acupuncture intervention that was directed specifically towards managing the symptoms related to the bladder, but also managing anxiety and general pain. If the patients were randomized to the control waitlist arm, they underwent the other similar preparations, like being wrapped up in warm blankets and were allowed to rest in a quiet space before going in and having their BCG treatment. So, there was no increased time in the clinic and there were no additional visits, which was important just in terms of optimizing the efficiency of care for the patients.
What were the key findings of the study?
We demonstrated that we could recruit, we could retain patients on the trial, and that it was safe. Importantly, patients loved the therapy, and about 95% of patients said that they were either very satisfied or extremely satisfied with the intervention. All the patients said that they were pleased with the acupuncture that they received, and about 75% said that they would refer other people going through BCG to acupuncture. Finally, when we did look at the patient reported outcomes, and it's a small study so we have to take this with a grain of salt...there was a trend towards reductions in pain score.
So, not stable pain scores or differences in pain scores between the arms but the patients in the acupuncture arm their pain scores across the 6 weeks declined. More importantly, across those 6 weeks their urinary symptoms declined. Patients in the acupuncture arm ended the trial with fewer urinary symptoms than when they started the trial with, which is virtually unheard of when it comes to folks going through BCG. That's an exciting signal and it's something that we are excited to pursue in future studies. I think it gives us enough of a reason to...take this concept forward and see if we can design a phase 3 study to get at that efficacy question in a much more detailed way.
Psutka SP, Veleber S, Siman J, et al. Phase I/II randomized clinical trial of in-clinic acupuncture prior to BCG in patients with high-risk non muscle-invasive bladder cancer. J Clin Oncol. 2023;41(16);4590-4590. doi:10.1200/JCO.2023.41.16_suppl.4590