It is estimated that prostate cancer will be diagnosed in nearly 268,000 men in 2022, making it the most commonly diagnosed cancer in men.1 Radiation therapy and surgical therapy are typically the primary treatment options for patients with prostate cancer. Options for radiation treatment include external beam radiation therapy (EBRT) and brachytherapy, wherein radioactive seeds are implanted into the prostate gland. EBRT has several modalities, based on regimen, with hypofractionated regimens called stereotactic beam radiation therapy (SBRT) delivering therapy over the shortest time.
As radiation therapy techniques such as dose escalation have continued to improve outcomes, the primary limiting factor is injury to surrounding structures. The organs primarily at risk include the bladder, urethra, and rectum, with the latter having the greatest risk.2 One of the best techniques to reduce radiation exposure to nontarget organs, and thereby decrease toxicity, is to increase the distance between the target and nontarget areas. In the setting of prostate cancer therapy, increasing the distance between the prostate and the rectum would accomplish this goal.2
Complications from pelvic radiation have been well documented. They include urethral strictures and subsequent urinary tract obstruction, gross hematuria, rectal bleeding, ureteral strictures, and even rectourethral fistulas.3 Toxicity rates vary based on the study referenced and radiation modality used. In general, patients undergoing conventional fractionation EBRT can expect very few early genitourinary (GU) or gastrointestinal (GI) toxicities; however, rates of late GU toxicities range from 6% to 14%, and up to 28% for rectal bleeding.3 In hypofractionation regimens, rates of toxicities tend to be higher as reported in the literature3: early GU toxicity occurs in 46% to 49% of patients but, in general, rates of delayed toxicity are lower. SBRT, also known as extreme hypofractionation, has similar rates of acute and long-term GI and GU toxicity as regular hypofractionation regimens.
The earliest reported use of spacer technology for prostate cancer treatment involved a trial of injecting hyaluronic acid into the perirectal fat to increase the distance between the prostate and the anterior rectal wall.4 Hyaluronic acid is a polysaccharide compound, located primarily in connective tissues, that can be degraded by hyaluronidase enzymes. The estimated stability of such polymers is up to 12 months.5 Patients in the trial underwent EBRT plus high-dose rate of brachytherapy for prostate cancer. On average, they reported that they were able to create 2 cm of additional distance between the prostate and rectum. Limitations to using hyaluronic acid include lack of radiation stability, with subsequent degradation after exposure to radiation.
Additionally, some authors have noted that utilization of cross-linked hyaluronic acid resulted in patients forming antibody responses, resulting in allergic reactions to hyaluronic acid-based compounds. A new hyaluronic acid-based prostate-rectal spacer is Barrigel®, which recently received approval from the US Food and Drug Administration (FDA). Approval was based on a randomized control trial (NCT04189913) investigating the ability of Barrigel® to increase the distance between the prostate and rectum, and thereby decrease rectal exposure to radiation.
Another type of spacing technology is a prosthetic balloon, commonly made of silicone, which is implanted before radiation and filled with saline. This technology has evolved, and biodegradable versions are now available that do not require removal after implantation.5 These balloons are often constructed with a polymer of polylactic acid and caprolactone.5 Some investigators have conducted trials in which they changed the solution placed in the balloon to further decrease the radiation dose delivered. One report demonstrated that filling a balloon with contrast can serve to lower radiation dosing to the anterior rectum when compared to filling with saline.6
The commonly utilized spacing technology involves the polyethylene-glycol (PEG)-based hydrogel compounds. The most well-known implementation of this is SpaceOAR™, which was approved by the FDA in April 2015 for use in prostate cancer radiation therapy.7 SpaceOAR was investigated in a prospective randomized phase 3 clinical trial, a trial that enrolled 222 patients, with 149 in the experimental arm (SpaceOAR) and 73 in the control arm.8 On average, the authors reported a mean increase in the space between prostate and rectum of 1 cm (from 1.6 mm to 12.6 mm). This correlated to a 78% relative reduction in radiation to the prostate. Toxicity rates between the two arms were similar in the acute phase; however, patients in the SpaceOAR group had a significant reduction in pain compared with those in the control arm. In the late phase (37 months follow up), rectal toxicity was substantially lower at 2% in the SpaceOAR arm versus 9% in the control arm.
No substantial difference in GU toxicity was noted between the two arms. DuraSeal® PEG gel is the other major product in this space; it has been demonstrated via off-label use to also reduce rectal radiation dose volumes.9 Although no direct comparisons between the two technologies have been conducted, it is reported that DuraSeal breaks down after 6 to 8 weeks compared to 3 to 6 months for SpaceOAR. This may limit its use in patients undergoing extended radiation courses.10 DuraSeal is less expensive than SpaceOAR, however, which may be of benefit in clinical scenarios where cost is a primary concern.
Insertion of rectal spacers varies based on the technology used; they can be inserted under local anesthesia or general anesthesia. Several authors report the goal as being to position the needle just anterior to the rectal wall and aim at the mid gland of the prostate in the axial imaging plane using transrectal ultrasound.10 Failure to achieve insertion is a rare complication but it does occur, primarily in patients undergoing salvage therapy in which the clinician is unable to perform hydrodissection after placement of the needle.10 Regardless of the technology used, the positioning of the spacer appears to stay stable throughout the treatment course.5 Another rarely noted benefit is that patients who are normally excluded from radiation therapy for prostate cancer owing to preexisting bowel conditions, such as inflammatory bowel disease, often become eligible with spacer placement.
Taking all types of spacers into consideration, acute GI complications, such as rectal bleeding and diarrhea, are 3 times less likely to occur in patients who undergo radiation with a spacer than in those who are treated without one.10 In conclusion, rectal spacers, most commonly the PEG- based compounds, improve rectal toxicity rates for patients undergoing radiation for prostate cancer while offering relative ease of administration.