In April 2015, the FDA cleared Augmenix Corporation’s hydrogel spacer for use in the US, as announced in their press release. The rectal spacer has been used in Europe since 2010. There are several kinds of rectal spacers: hydrogel, hyaluronic acid gels, biodegradable balloons, and collagen. They all entail injection of a biodegradable substance into the space between the rectum and prostate in order to reduce the radiation dose to the rectum. There have been several studies already published on its use with various kinds of radiation- IMRT, 3D-CRT, SBRT, protons, low dose rate brachytherapy, high dose rate brachytherapy, salvage radiation after primary prostatectomy, and salvage brachytherapy after primary radiation.
Approval was based on favorable results from a randomized clinical trial among 222 men in 20 centers. The study by Pierczonka et al. has now been published. The study design specs were:
- · 222 men who received 79.2 Gy in 44 fractions
- · 149 got fiducial markers plus the rectal spacer
- · 73 got fiducial markers only (control group)
The results were as follows:
- · No spacer sensation following application.
- · Mild transient rectal events in 10%.
- · Average separation added was 12.6 mm.
- · Complete absorption by 12 months.
- · 97% of the men with a rectal spacer had a reduction of more than 25% in the volume of the rectum that received 70 Gy.
- · 100% of men with a rectal spacer met dose constraints.
- · 92% of control group men met dose constraints.
- · Patient-reported bowel-related quality of life declined less for the rectal spacer group than for the control group at 6, 12, and 15 months.
- · There were no serious rectal adverse events. There were no differences in acute rectal toxicity whether the spacer was used or not. Adverse acute (earlier than 3 months) rectal events were noted in 34 percent of those who got the SpaceOAR gel, and 32 percent of those who did not — no difference.
So the hydrogel spacers were safe, well tolerated, and reduced the rectal dose somewhat. We note that the vast majority of radiation plans meet normal rectal dose constraints even without it.
This confirms what we've seen in other studies about acute rectal toxicity. In a study from Germany last year, Uhl et al. reported acute GI toxicity of Grade 0 or 1 of 88%, and Grade 2 of 12%. In a recent study of an IMRT dose of 79.2 Gy by Michalski et al., Grade 0 or 1 GI toxicity was reported by 90% of patients, and Grade 2 by 10% – nearly identical to the results with rectal spacers.
As for late rectal toxicity (those that occurred between 3 and 15 months after treatment) there were only 5 cases of rectal symptoms (7 percent) at all in the group that did not have the spacer, and 4 of the 5 were mild — Grade 1 bleeding and urgency. It should be noted that Grade 1 symptoms are so mild that they are often not even reported, so I like to group Grade 0 and 1 together. There was only one serious rectal event (Grade 3 proctitis) in a man who did not get a spacer. There was a single late-term Grade 1 rectal adverse event in a man who got a spacer.
Confirming that finding, the Uhl et al. study reported no late GI toxicity of Grade greater than 1. This seems consistent with the statement in the Pierczonka et al. study also that there were no serious rectal adverse events. For a historical comparison, we can look to a 10-year study of men treated with 81 Gy IGRT/IMRT at Memorial Sloan Kettering Cancer Center, arguably among the best at this kind of therapy. Alicikus et al. reported late-term gastrointestinal toxicity of Grade 0 or 1 in 97% of patients, Grade 2 in 2%, and Grade 3 in 1%. So we see that severe late term rectal toxicity is not much of a problem using best practices of IGRT/IMRT even without a rectal spacer.
Late-term rectal events are not a serious problem with modern radiation techniques. Acute rectal adverse events are a much bigger problem, but the SpaceOAR gel did not help at all with that.
I also notice very serious use of anesthesia with the rectal spacer, including general (36 percent), monitored (25 percent), local (31 percent), conscious sedation (6 percent) and other (11 percent). This increases the cost, and raises safety concerns (there were no anesthesia-related incidents), and limits the number of patients who are eligible for it. Antibiotic prophylaxis is required with it as well.
This raises the question: Is reducing the toxicity for 3% worth the cost of adding rectal spacers for all treated men? In Europe, the cost of a SpaceOAR gel injection was 1,700€ ($1,850). I think the decision about whether to use it should not be routine. It may have a very useful role in men with bowel inflammation, a history of rectal issues (hemorrhoids, for example), or anatomic abnormalities that make the rectal dosimetry problematic. There will always be that residual 1 or 2 percent who are sensitive to radiation for some reason, and who may benefit. I’m glad that there is this option for those few who may benefit from it.