Protons 101: A recent randomized study of rectal spacing.
Do we learn anything new from the latest rectal spacing trial?
As always, author of one: if you see an omission or think I missed something, please reach out or comment below.
Today is a quick update post as new data was just released this week. Just a few days ago, I looked at the original rectal spacing data and came away rather unimpressed.
February 9th we had the release of more prospective rectal spacing data (ref 1). This is a rather highly advertised first ever trial of rectal spacing in hypofractionated prostate cancer patients. This study clearly adds to our dataset and so we’ll quickly look at this study and see if adds significantly to the prior data. Below is the Barrigel website main graphic.
First off, as with any prospective trial, the data is generally far better than anything retrospective. The authors and supporters of the trial need to be commended for carrying out the study trying to scientifically define the correct path forward.
We’ll go rather quickly.
It was a multicenter trial with 260 patients: 2:1 in favor of Barrigel placement. Margins were allowed to vary - which I do think introduces significant opportunity for differences in the arms simply due to margin differences. (margins varied from 5mm-10mm with 5mm consistently posteriorly). Not wrong per say but important to note.
The trial used 9-12 cc - so 3 or 4 vials of Barrigel. In my experience, this is more than they might recommend as you pay per vial and is more costly - 2 or 3 is quite common recommendation so that would be one less. Many of our current cases have 6cc - 2 vials.
Primary endpoint was "at least" a 25% reduction in rectum V54 which is a non-validated endpoint. It probably is fine as a general marker for “improved dosimetry” but meeting that metric doesn’t mean better outcomes. It simply means better dosimetry.
Dosimtry Outcomes: Study did show dosimetry improvements. I believe that conclusion even with leeway in the margins. p value highly significant.
Clinical outcomes: Gr2 or higher rectal toxicity did show a reduction 13.8% to 2.9%, p=0.01. This is a validated clinical endpoint. But, QoL surveys were less impressive and showed only a trend at 3 months (p=0.13) in favor of rectal spacing and by 6 months, there was no difference. No urinary or sexual function differences.
COI: I’ve seen people discuss the COI and there are quite a bit of potential conflicts with a number of authors. Generally I don’t have much trouble with MDs being compensated for time. In this case, the $$$ are not insignificant with the lead author, as one example, showing 2018 compensation over $100,000 from relationships with the rectal spacing industry. More broadly $216,000 for all-time, from all sources. For comparison, my data shows $1497 for all-time, all sources. (ref 2)
My summary: A relatively non-impactful randomized trial
Both this and the prior trial I discussed earlier, seem to have some issues (the original with analysis and writeup and this mainly due to potential COI) but in general both point to a little less rectal toxicity. How often are the differences clinically important is a more nuanced question, but Gr2 toxicity is validated and often used.
Despite no findings of significant implant toxicity in any prospective study, there is some minimal but non-zero risk - infection, procedural, stopping anti-coagulants etc. No free lunches in this world.
This trial again leaves off any sexual impact and any bladder impact which is consistent with my prior assessment of the data. Overall, I think it is randomized data that ultimately doesn’t add much. It lets Barrigel advertise head to head with SpaceOAR with a study showing that rectal spacing shows reductions in Gr2 rectal toxicity with little other impact.
Finally, to me, the Barrigel site advertising is appropriate. They deserve credit for a more subdued marketing approach. I don’t think they overstate the results and that is nice to see in today’s world. I think the SpaceOAR webpage is more typical where debatable data is pronounced as fact - primarily in the bladder and sexual function data which has not be repeatable (at best).
COI: As stated in my prior article, I do typically utilize rectal spacing. No COI, just good to understand my practice - see prior post for greater details regarding that decision.
REFRENCES:
Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy
https://jamanetwork.com/journals/jamaoncology/fullarticle/2801296
OpenPayments CMS site:
https://openpaymentsdata.cms.gov/physician/319127
Special shoutout to whoever this is below for helping me find that site and this article»
elementaryschooleconomics on the https://forums.studentdoctor.net/