New device adds clinical benefit and reduces risk with prostate radiotherapy

BERKELEY, CA USA (UroToday.com) -

SpaceOAR® System Protects Organ At Risk During Prostate Cancer Treatment

On April 2, 2015, SpaceOAR® System received clearance from the Food and Drug Administration as the first and only “spacing” device to protect the rectum during radiation treatment of prostate tumors.

Radiation oncologist John E. Sylvester, MD, from 21st Century Oncology, in Bradenton, FL, was a principal investigator in the recently completed phase III study to evaluate the safety and tolerability of the SpaceOAR® system.

Here, Dr. Sylvester speaks to UroToday.com about treatment and side effect considerations with radiotherapy for prostate cancer, and explains features and benefits of the SpaceOAR® System as it shortly becomes available to the wider oncology community. Written By: Barbara Jones

sylvester john md
John E. Sylvester, MD

UroToday:There is potential risk to adjacent organs and structures when radiation is directed at a tumor. Can you describe the safety considerations in circumstances where radiation therapy is used for prostate tumors?

Dr. Sylvester: When you use radiation therapy for prostate cancer, either external beam radiation therapy, IMRT, or brachytherapy, and are delivering a high dose to the prostate—and to the edge of the prostate—you want to limit the dose to the rectum. The rectum is the dose-limiting structure, also known as the organ at risk (OAR).

UroToday: What are ways in which you try to avoid or limit damage to the rectum with radiation therapy?

Dr. Sylvester: Throughout the whole body, the field of radiation oncology has developed what are called dose-volume histograms, so that we know what dose a particular volume of rectum can tolerate safely. What we want to do, for instance, is make sure less than 20% of the rectal volume is getting 70 Gy radiation. You want that to be less than 20%. The lower the percentage the better.

Another thing we do is take a CT scan of the patient in the treatment position every day before we turn the beam on to make sure we’re hitting our target. For instance, if the rectum is full of gas, it will push the rectum anteriorly up into the beam. So, by conducting the CT scan first, we will see that and can lower the table so that the prostate is in the beam, but not the rectum.

And, to stop the prostate from moving while the beam is on, we put a small rubber tube/balloon in the rectum each day and inject air into it. This inflates the balloon in the rectal vault and holds the prostate still while the treatment beam is on. So, when we do the scan, we have it all lined up and know that it is not going to move.

UroToday: How does the SpaceOAR® system, a prostate cancer spacing device, contribute to strategies like the one you just described to prevent damage to the rectum during radiation for prostate cancer?

Dr. Sylvester: What SpaceOAR® does is add to this. It actually takes the space between the prostate and the rectum—a very small, couple of millimeters of space and increases it to 12 ½ to 13 millimeters, which is a lot of space. It moves the dose radiation further away from the rectum. We couldn’t do that before.

UroToday: Could you describe how the SpaceOAR® system is administered?

Dr. Sylvester: Under local or general anesthetic, or IV sedation, we take an 18-gauge needle and insert it through the skin of the perineum at an angle so that it goes into the natural space posterior to the prostate and anterior to the rectum – an approximately 2 millimeter space.

We inject 10 ccs of sterile saline into the space, called hydrodissection, to verify correct needle placement. Leaving the needle in place, we then take the syringe with the sterile saline off and attach the SpaceOAR® applicator to that needle and inject the SpaceOAR® hydrogel. The hydrogel is initially injected as a liquid which expands the space between the prostate and the rectum.

Within about 10 seconds the liquid solidifies into a gel in the space just created by the water dissection. This will keep the prostate away from the rectum for an average of 3 months. Then it slowly dissolves and disappears.

UroToday: What is the SpaceOAR® hydrogel made of?

Dr. Sylvester: SpaceOAR® hydrogel is very similar to other hydrogels used in other medical procedures. Based on polyethylene glycol (PEG), these products are non-toxic and safe, and are used in sensitive areas of the body.

UroToday: How does it differ from these other hydrogel products and applications?

Dr. Sylvester: It differs in that it stays in gel-like form for a longer period of time – at least 3 months, which is important for radiation. External beam radiation is a 2-month process. Also it is easier to use as it takes 10 seconds to solidify while other substances solidify too fast (in ~2-3 seconds)

In patients receiving seed treatment, seeds are radioactive for several months, so you want that prostate to stay away from the rectum during that entire period of time. SpaceOAR® hydrogel was designed to stay in place for 3 months.

UroToday: During the time the hydrogel is a solid is the patient aware of its presence?

Dr. Sylvester: It is not really hard, it is firm. And no, actually none of the patients I’ve treated can feel anything different.  They report that everything felt normal; bowel movements felt normal. They didn’t really notice anything.

UroToday: Could you speak a bit about the phase III SpaceOAR® pivotal study, which was completed toward the end of 2014 and awaits publication?

Dr. Sylvester: It was a randomized, controlled trial, with 2-to-1 randomization. Twenty centers were involved in the study. The plan was for 222 patients, which was accomplished. A total of 149 subjects got the SpaceOAR® gel injection, and 73 were control patients. The study was blinded, so patients did not know whether they had the SpaceOAR® system or not. Eligible patients were low-risk and favorable intermediate-risk patients.

We did a whole treatment plan on the  study patients, with CT and MRI scans first, without the SpaceOAR® hydrogel. Then we brought them into the OR and placed three gold markers into the prostate, which is standard practice for image guidance. Immediately after the placement of the gold markers, while subjects were still in the OR, we opened up the randomization envelope to learn whether they got the SpaceOAR® material or nothing.

If the patient was to receive the SpaceOAR® hydrogel, we injected that. It took about 3 to 4 minutes to do the SpaceOAR® injection. And then we did another treatment planning simulation on them, just like the first one, for comparison purposes, and to do the real treatment plan. Then they received the 44 treatments 79.2 Gy of radiation with image-guided approach. We followed them up at 3, 9, 12, and 15 months post-SpaceOAR® injection with specific patient questionnaires—CTCAE (Common Terminology Criteria for Adverse Events), EPIC—quality of life questionnaires. The patients filled out these questionnaires before treatment and at each of the follow-ups, so that we could document whether or not they had less side effects because of the SpaceOAR® – although the primary endpoint of the study was to document a reduction in the dose of the radiation to the rectum.

UroToday: What were the findings from this trial?

Dr. Sylvester: The endpoint was met easily. We had a dramatic reduction in the primary endpoint of the dose of radiation to the rectum, on the order of a 73% reduction in rectal V70 radiation dose looking at the pre-SpaceOAR® plan versus the post-SpaceOAR® plan.

We also saw a reduction in bowel side effects; specifically, rectal pain was less with the SpaceOAR® hydrogel. Among the SpaceOAR® patients, only three patients had grade 1 side effects and nobody had grade 2 or greater side effects after 3 months. Among the controls, there were more grade 1-3 side effects.

The statistically significant finding was that the SpaceOAR® patients had less rectal toxicity compared to controls, and pain was significantly less in the SpaceOAR® patients than in controls.

UroToday: How would you summarize the benefits the SpaceOAR® system may offer clinicians over the former alternatives, as it soon becomes widely available?

Dr. Sylvester: It is a very nice additive approach to what we are already doing. It only takes a few minutes to inject the gel (after the patient is positioned properly with ultra sound in place, etc.), and we are seeing much lower rectal doses. Hopefully, it will allow us to go to higher total doses of radiation to the prostate. Every study that’s looked at radiation therapy for prostate cancer has shown that the higher the doses you give, the better chance you have of eliminating the cancer.

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A Patient Speaks About His Experience With the SpaceOAR® System

Prostate cancer patient “Bill” elected to receive radiotherapy when his physician explained his treatment options. His treatment coincided with patient recruitment for the phase III clinical trial evaluating the safety and tolerability of the SpaceOAR® system. Bill joined the trial as one of 222 patients who were randomized either to SpaceOAR® or nothing. Retrospectively, Bill learned that he was in the active treatment (SpaceOAR®) arm. He responded to a few questions from UroToday about his experience with the device.

UroToday: I understand you received radiation therapy to the prostate. How did you learn about the SpaceOAR® system? What did your physician tell you about it?

Bill: My urologist was pushing for surgery, but as soon as the word catheter came up, I was like … “I don’t think so.” Dr. Sylvester was very specific about the clinical trial and the SpaceOAR® system.

UroToday: What things did Dr. Sylvester say regarding the role the SpaceOAR® system plays during radiotherapy, and the protection it provides?

Bill: I understand that the radiation can hit other organs. It was my understanding that the whole balloon thing is just very uncomfortable. It (SpaceOAR®) separates the prostate from the rectum. It is put in and it leaves your body over the course of time.

UroToday: About the SpaceOAR® placement… were you uncomfortable during the process?

Bill: No, not at all. When they put in the gold markers, at the same time they inserted the SpaceOAR®. I was knocked out during the process. It was completely uneventful; no different than getting a colonoscopy.

UroToday: Did you experience any side effects, any uncomfortable symptoms while the SpaceOAR® was in place? If so, how long did the side effects last?

Bill: I wasn’t aware of anything. There was no discomfort, no pain. I just carried on, business as usual. There were a few days after the radiation when I might be a little more tired than usual. Three of four times I had two radiation treatments in the same day. Other than that, my life was completely normal.

UroToday: It sounds like this was something you endured with very little discomfort, if any at all…

Bill: The whole thing, from start to finish—the entire 44 consecutive days of treatment—everything was pretty much a piece of cake. I am really happy the FDA has approved it.

The SpaceOAR® system, (OAR referring to “organ at risk”) is a temporary injectable gel that protects the rectum of men undergoing radiation therapy for prostate cancer. It is the first and currently the only prostate cancer spacing device to receive Food and Drug Administration (FDA) clearance.

Read related content:

Augmenix announces FDA clearance of SpaceOAR® System
Application of a hydrogel spacer for postoperative salvage radiotherapy of prostate cancer
Feasibility of and rectal dosimetry improvement with the use of SpaceOAR® hydrogel for dose-escalated prostate cancer radiotherapy
Hydrogel injection followed by treatment planning during radiotherapy of prostate cancer, "Beyond the Abstract," by Michael Pinkawa, MD
Application of a spacer gel to optimize three-dimensional conformal and intensity modulated radiotherapy for prostate cancer

Written by Barbara L. Jones, medical writer for UroToday.com.

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