'Good Tool': Hydrogel Spares Rectum From Radiation

3-Year Data Show Durable Safety Effect

Nick Mulcahy

September 28, 2016

BOSTON — An injected hydrogel that temporarily creates space between the otherwise contiguous rectum and prostate gland continues to benefit patients 3 years after radiation treatment for prostate cancer, according to final safety results from a US multicenter, phase 3 clinical trial.

The extended safety benefits included reducing radiotherapy's toxicity and minimizing changes in quality of life (QOL).

The hydrogel (SpaceOAR, Augmenix) is a "spacer" that, after injection, remains in place for approximately 3 months and then is eventually absorbed by the body, said lead study author Daniel Hamstra, MD, from Texas Oncology in Irvine. The product was cleared for use in the United States by the Food and Drug Administration last year.

The temporary space is intended to decrease the amount of rectum that is exposed to radiation, he said. The rectum and bowel are acknowledged to be the organ most vulnerable to damage from radiation treatment to the nearby prostate. That physical proximity limits the intensity of radiation that can be delivered to patients with prostate cancer.

In the first clinical trial of a device that creates space between the rectum and prostate, 222 men with low-risk prostate cancer were randomly assigned 2:1 to fiducial marker placement plus hydrogel treatment and to fiducial marker placement alone (ie, controls) before intensity-modulated radiotherapy (IMRT). The radiotherapy (79.2 Gy) was delivered over 8 weeks in 44 fractions.

The hydrogel application resulted in an average of 12.6 mm of perirectal space.

The median follow-up was 37 months for both treatment groups.

Here at the American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting, Dr Hamstra reported on the primary safety endpoint: the proportion of hydrogel and control patients experiencing grade 1 or greater rectal or procedural adverse events (AEs).

The control group had higher rates of AEs overall, he revealed.

With regard to rectal toxicity, the control group, when compared with the hydrogel group, had a higher incidence of both grade 1+ (9.2% vs 2.0%; P = .028) and grade 2+ (5.7% vs 0%; P = .012) events.

With regard to urinary incontinence, the control group had more grade 1+ events (19.6% vs 4.3%; P = .003). But there was no difference between study groups in grade 2+ urinary toxicity (P = .7).

Dr Hamstra also reported that there was no difference in response to radiotherapy in the study; no biochemical failures have occurred to date, and the median prostate-specific antigen at last follow-up was 0.5 ng/mL in each group (P = .28).

These data are important, said Eric Horwitz, MD, from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was not involved in the study.

"The reduction in the rectal side effects indicate that they are durable," he told Medscape Medical News. With gastrointestinal toxicities, 3 years is the point at which "you know they are going to be chronic," he explained.

Furthermore, the rates will likely not change with any further follow-up. "What you see at 3 years is what you are going to see," Dr Horwitz said.

What you see at 3 years is what you are going to see. Dr Eric Horwitz

Dr Horwitz acknowledged that the hydrogel is unique and effective: "There is no other spacer. I think it is a good tool."

While he knows of centers that use the spacer, Dr Horwitz said Fox Chase is not one of them. "I know radiation oncologists that are happy with it. But we don't use it because we are a high-volume center with a very experienced staff and a record of minimal side effects. The spacer is also invasive," he said.

Volume of Radiation Is Also Reduced

The study also included QOL measurements of the patient groups, using the Expanded Prostate Cancer Index Composite (EPIC), which was collected at baseline and serially.

Dr Hamstra summarized the EPIC findings for bowel events and QOL declines. Overall, for the hydrogel group compared with the control group, there was a clinically meaningful improvement in bowel QOL with 70% reduction in the risk for bowel QOL declines of 5 and 10 points, he said. In other words, a lower incidence of men in the hydrogel group had a bowel-related QOL decline than the men in the control group.

The urinary QOL findings were similar. Dr Hamstra summarized by saying that there was a 50% relative reduction (9% absolute) in the likelihood of a large decline (12 or more points) in urinary QOL among the men in the hydrogel group.

Last year, the study authors published 15-month data from their study. In that publication, they reported that the hydrogel had resulted in a significant reduction of radiation volume to the rectum.

Specifically, they reported on the study's primary effectiveness endpoint: the proportion of patients achieving greater than 25% reduction in rectal volume receiving at least 70 Gy (rV70) because of spacer placement. This measure was evaluated by looking at pre- and post-spacer dosimetry treatment plans. There was a significant reduction in mean rectal V70 (12.4% to 3.3%; P < .0001), they reported (Int J Radiat Oncol Biol Phys. 2015;92:971-977).

"The radiation plans were different due to the spacer. There were much lower doses to the rectum after the spacer was placed," said Dr Hamstra.

The 25% reduction was deemed clinically relevant because it approximates the reduction achieved with progressing from 3-dimensional conformal RT to IMRT.

The study was funded by Augmenix, maker of SpaceOAR. Dr Hamstra is a consultant to multiple companies, including Augmenix. Dr Horwitz has disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting. Abstract LBA-6. Presented September 27, 2016.

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

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