Edward Soffen: Welcome to the third part of the series of the spacer wars trilogy. I'm going to be talking about the BioProtect balloon and a quote from Luke Skywalker from Star Wars was that you can't stop change any more than you can stop the sun from setting. My disclosures are that I've been a consultant for Boston Scientific and BioProtect and I was an investigator in both of the pivotal studies for SpaceOAR and BioProtect, and I've used Barrigel since it was FDA approved earlier this summer.

So change is evolution. Luke Skywalker said you can't stop change, you cannot stop evolution. And that pertains also to the rectal spacing issue. SpaceOAR came out seven years ago and it was a good start to the problem that we as radiation oncologists have been facing for years, the rectal toxicity, the proximity of the rectum to the prostate, but it didn't always go where you wanted it. Even after several thousand of placements, sometimes it goes off to the side, sometimes it goes into the rectal wall. You just cannot control it all the time and you couldn't see it. So then upon our recommendation to Boston Scientific, they added a little bit of contrast to it and suddenly you could see it and maybe it wasn't that good to be able to see it because we could see a lot of our mistakes, but you still couldn't control where it was going.

Then this past summer, Barrigel was FDA approved and suddenly you could sculpt. You had a little bit more control, not complete control, but you still couldn't see it. And I disagree, I think it's hard to see on CT simulation. At my therapist, even though we have excellent cone beam CT, it is not quite as clear as the SpaceOAR view or the BioProtect balloon. So the study that I was involved in was a prospective randomized trial in eight US sites. We enrolled 222 patients with a 2:1 randomization to get the balloon or not. We enrolled patients throughout COVID. It was quite difficult. Our efficacy endpoints were looking at reducing at least 25% of the rectal volume, receiving 70 gray in 75% of the patients. We looked at safety endpoints including rectal implantation adverse events. The secondary endpoints were the distance of the rectal wall to the prostate at the beginning and on the last day of radiation, we looked at dosimetry and quality of life.

And finally the balloon resorption at six months. Here are the results. 97.9% of subjects gained rectal dose reduction and greater than 25% of V70 after implantation. The rectal volume receiving 70 gray was 7% initially after post-implantation, it was 1.1%. That's 84.8% mean V70 reduction. The V60, V50, V40, they were all also reduced. We don't know exactly what that means, but it probably has to do with some of the non-reportable rectal toxicities like rectal urgency and frequency. There were no unanticipated adverse events. There was a 5% reduction in rectal toxicity in the balloon group as compared to control. The balloon height remained robust throughout the treatment. There was only approximately one millimeter loss in height over the course of radiation. And at six months, almost all of the balloons had completely resorbed. All of them were absorbed except for two, which were almost resorbed.

So in my opinion, the advantages to the balloon are there is uniform and symmetrical separation from base to apex. If you don't like the position of the balloon on ultrasound, you can deflate it, move it, reposition it, reinflate it, until you like where it is, center from base to apex and then you can discharge the balloon. You get 15 to 17 millimeters of displacement. You cannot achieve that with the other spacing devices. They're just not enough volume with the Barrigel, which is either 9 or 12cc or the SpaceOAR view, which is 10cc, it's a stable configuration for three months. It's gone by six months. You could deflate the balloon if you wanted by sticking a needle in if for some reason you wanted to.

It is virtually impossible to place in the rectal wall. We don't have a sharp beveled needle. We have a thin, it's almost like a Bic pen dilator. You can see it in Denonvilliers' fascia. There is virtually no way that you can place it into the rectal wall. There were no complaints of rectal discomfort. It's highly visible on ultrasound and CAT scan. You don't have to get that post implantation MRI. It's simple for the physician to contour, the physicists and dosimetrists love it and the therapist will praise you for it. One picture is worth a thousand words. Here's an axial and sagittal image on CT sim. You can see the balloon has a little bit of contrast, less than five ccs of contrast in the saline. And you see beautiful images on CAT scan and on cone beam CT. So in quick comparison, the spacing is more robust. It's symmetrical, it's consistent. You can see it on ultrasound, you can see it on CAT scan. You can control the positioning better than the Barrigel. There's no beveled needle. So like I said, it's virtually impossible to place into the rectum.

And theoretically, if you're worried about microscopic extracapsular extension being displaced through the liquid of the spacer, view out into the area where you don't get high dose radiation. There's no liquid here. You just inflate the balloon. So the likelihood of spreading extracapsular cells is virtually nil. So final analysis, if you believe rectal spacing is important in the treatment of prostate cancer with radiation, you should consider it a standard of care no matter which spacing device you're using. And there are few exceptions for that. It improves the dosimetric advantage, reduction to the rectum and bladder, with significant decrease in grade two and higher rectal toxicity. And in my opinion, the most symmetrical, robust and visible product with a precise decay is clearly the balloon. Now, as soon as this is FDA approved, we're going to do a phase III randomized trial that will ultimately prove the spacer wars. Thank you.