Dr. Richards on the effect of Agent Orange exposure on BCG treatment in NMIBC

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“We wound up finding that there was no difference in recurrence, no difference in secondary events, and no difference in our survival end points whether or not you were exposed to Agent Orange,” says Kyle A. Richards, MD, FACS.

In this video, Kyle A. Richards, MD, FACS, highlights the background and notable findings from the study “The impact of Agent Orange exposure on non-muscle invasive bladder cancer outcomes”. Richards is an associate professor of urology at the University of Wisconsin-Madison.

Video Transcript:

Could you describe the background of this study?

Agent Orange, also known as dioxin, was a herbicide that was used during the Vietnam War in Operation Ranch Hand. It was estimated that 45 million liters of Agent Orange was sprayed in Vietnam alone from 1965 through 1970. So, many veterans of the US armed forces that were stationed in Vietnam likely had this exposure. We know that one of the primary causes of bladder cancer are environmental exposures such as Agent Orange and other carcinogens that are present in the environment. Recently, bladder cancer was added to a list of cancers that had a link to Agent Orange. So, it's been fairly well established that that Agent Orange could cause bladder cancer. The purpose of our study, though, was to see if patients who had an exposure–so patients that had bladder cancer that were exposed during their service time–if that exposure led to worse outcomes. We don't really understand the mechanism of action of how Agent Orange causes bladder cancer, but we do know that there's a strong association with it. We wanted to ask the question, if you are exposed, did you have worse outcomes? Did it alter the biology of the disease? There were some previous studies that showed that Agent Orange may provide an effect against some of the apoptosis that is caused by BCG. So, we specifically wanted to look in a population of patients that were treated with BCG to test that hypothesis.

What were some of the notable findings?

We used national VA databases to build the cohort. We were able to identify patients with bladder cancer that were diagnosed from January of 2000 through December of 2010. Then we had follow-up through 2018. As I mentioned, we wanted to focus on patients that had non-muscle invasive bladder cancer that were also treated with BCG. That allowed us to have a final sample size of 7651 patients. So, we had a fairly robust sample size of patients. And out of those patients, we had a total of 753 that had a documented exposure to Agent Orange. To have that documented within the VA, the Veteran Affairs health system, the veterans have to prove that they had an exposure. There's a lot of administrative work that goes into showing that they had this exposure, so we do believe that they were exposed. So, 753 patients were exposed. The primary outcomes we looked at were recurrence. We also looked at secondary events which were a surrogate for progression. Then we looked at bladder cancer-specific survival and overall survival. We broke down the patients by Agent Orange exposed versus non-Agent Orange exposed. We wound up finding that there was no difference in recurrence, no difference in secondary events, and no difference in our survival end points whether or not you were exposed to Agent Orange. So, that was good. We felt like that was good news. It was a little bit surprising in the sense that we had hypothesized that the patients that had BCG treatments and Agent Orange exposure based on the mechanistic evidence, maybe would have had worse outcomes. But in this study, we did not see that.

This transcription has been edited for clarity.

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