Earlier this month, the US Food and Drug Administration (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, biogradable 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. is to be presented at the upcoming annual meeting of the American Urological Association, but has not yet been published in a peer-reviewed journal. The study design specs were:
- 222 men with T1/2 localized prostate cancer were treated with 79.2 Gy in 44 fractions.
- 149/222 got fiducial markers plus the rectal spacer.
- 73/222 got fiducial markers only (control group)
The results were as follows:
- No spacer sensation following application.
- Mild transient rectal events in 10 percent.
- Average separation added was 12.6 mm.
- Complete absorption by 12 months.
- 97 percent of the men with a rectal spacer had a reduction of more than 25 percent in the volume of the rectum that received 70 Gy.
- 100 percent of men with a rectal spacer met dose constraints.
- 92 percent 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.
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. Does the reduction in rectal dose translate into meaningful reductions in gastrointestinal (GI) toxicity? Since we don’t have the details of gastrointestinal toxicity for this study, we must look at rectal spacer outcomes as reported in other published studies and in light of typical rectal toxicity reported for contemporary IGRT/IMRT treatments as historical controls.
The abstract of this study doesn’t provide any information about acute rectal toxicity. However, in a study from Germany last year, Uhl et al. reported acute GI toxicity of Grade 0 or 1 of 88 percent, and Grade 2 of 12 percent. 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 percent of patients, and Grade 2 by 10 percent – nearly identical to the results with rectal spacers.
As for late rectal toxicity, 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 percent of patients, Grade 2 in 2 percent, and Grade 3 in 1 percent. 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.
This raises the question: Is reducing the toxicity for 3 percent 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. It is good that radiation oncologists will have this protective option for certain, well-selected patients.
Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.
Filed under: Management, Treatment | Tagged: outcome, radiation, rectal, SpaceOAR, spacer |
THE "NEW" PROSTATE CANCER INFOLINK 
The results from the US pivotal trial are now published in the Red Journal.
The SpaceOAR arm demonstrated a 73% reduction in rectal V70 vs. control and a 71% reduction in late rectal toxicity (7% in control vs. 2% in the SpaceOAR at only 15 months follow-up). Also, patients in the SpaceOAR arm had 46% fewer significant declines in bowel QOL than those in the control arm.
Hmmm … According to the abstract of the article in the Red Journal, the differences in last GI toxicity were only barely statistically significant (p = 0.04), which would seem to concur with the point that Allen was making above.
Thank you for posting that link, which includes a link to the full text. It confirms what I suspected. 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.
As far as incidents of rectal toxicity 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.
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 reinforces my point that 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. True, 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.
I’d be interested to hear of any methods to identify the patients who might benefit. Just doing it for everyone might not work, but if you could identify the 1 to 2 percent, it could save those patients many problems later.
Thanks Allen, Sitemaster and other participants for this article and discussion.
Considering my own experience with 78 Gy IMRT TomoTherapy (plus 46 Gy pelvic dose) in 2013, grade 0 and 1 long-term side effects which I have experienced would not have made this spacer technology worthwhile, though I did wonder about it at the time. Of course I’m hoping I continue to do as well as I have since getting past the acute phase.
This discussion up front would have eased my mind a bit and I would have dispensed with thoughts about use of a spacer. All this said, I’m glad the spacer is approved to help the few who will really need it and whose doctors recognize that need.
This discussion should help others.
I think it’s a good idea to visit a proctologist before having any kind of radiation to identify and possibly clear up issues before radiation exacerbates them. Colitis, irritable bowel syndrome, internal hemorrhoids. fissures, etc., can be identified as possible indications for a rectal spacer.
Admittedly reducing toxicity in current protocols is a difficult undertaking. However, we should not forget that the current protocols were shaped by the prostate-rectum proximity. We have spent decades making compromises between rectal toxicity and cancer recurrence. Even though the long-term toxicity is relatively low, is 40-44 fractions with not-insignificant recurrence rates where we really want to be?
The real potential for prostate-rectum spacers is that they should enable dose escalation and extreme hypofractionation. Being able to provide a more definitive, cost-effective, and convenient treatment should be a really big deal.
The discussion should not be centered around the value of marginal improvements in current protocols, or about use in select patients, but about enabling significant protocol and outcome improvements going forward.
Patrick,
I agree that the traditional 40-44 IMRT treatment schedule may soon become outmoded. (I’ll wait for the comparative clinical trial results expected this year to see for sure.) It’s not all about dose though — sometimes ADT has a role to play, and the risk level of the patient may enter into it as well. Recently we reported a study by Nabid et al. that showed that for intermediate-risk patients, higher dose EBRT was inferior in biochemical recurrence rates to lower dose EBRT with ADT. We still await a long-term trial that shows a survival benefit, and not just a recurrence benefit, to dose escalation.
The rectum is only one of the organs at risk. The bladder, the femoral heads, the urethra, the penile bulb, and the bowel are at risk as well. Every indication is that the biologically effective dose levels reached by current hypofractionated protocols and combo therapies have already reached the end of the steep part of the dose/response curve. Bioequivalent doses beyond 200 Gy have not demonstrated any clinical benefit thus far.