Medical Policy
Subject: Perirectal Spacers for Use During Prostate Radiotherapy
Document #: SURG.00143Publish Date: 07/06/2022
Status: RevisedLast Review Date: 05/12/2022
Description/Scope

This document addresses the use of perirectal spacers placed prior to prostate radiotherapy as a method of rectal displacement. Such products include SpaceOAR® (Boston Scientific, Marlborough, MA.), an injectable liquid hydrogel product intended to create distance and serve as a spacer between the prostate and the anterior rectal wall in individuals undergoing radiotherapy for prostate cancer.

Position Statement

Medically Necessary:

Use of perirectal spacers during prostate radiotherapy is considered medically necessary when all of the following criteria are met:

* Daily external beam radiotherapy delivered in 28 fractions or fewer treatments.

Investigational and Not Medically Necessary

Use of perirectal spacers is considered investigational and not medically necessary when the criteria above are not met.

Rationale

Stereotactic Body Radiotherapy (SBRT)

 In 2017, Jones and others reported the results of two parallel cohort studies involving subjects being treated for prostate cancer with stereotactic body radiotherapy. In one study subjects were treated using a rectal balloon (n=36) and in the other, with SpaceOAR (n=36). The SpaceOAR group achieved significant dosimetric superiority over the rectal balloon group with respect to the maximum dose to the rectum (42.3 versus 46.2 Gy), dose delivered to 33% of the rectal circumference (28 versus 35.1 Gy), and absolute volume of rectum receiving 45 Gy (V45Gy), V40Gy, and V30Gy (0.3 versus 1.7 cc, 1 versus 5.4 cc, and 4.1 versus 9.6 cc, respectively). No significant differences between the two groups with respect to the V50Gy of the rectum or the dose to 50% of the rectal circumference was reported. The V18.3 Gy of the bladder was significantly larger with the rectal balloon (19.9 versus 14.5 cc). The authors concluded that the rectal balloon did not outperform the injectable spacer gel in any measured rectal dose parameter.

In a retrospective, single institution study, Hwang and others (2019) reported on the safety and efficacy outcomes of individuals with low- or intermediate-risk prostate cancer who were treated with SBRT (n=50). The median follow-up time was 20 months (range 4 to 44 months). Acute grade 2 genitourinary (GU) toxicity developed in 30% of participants during radiotherapy. Grade 2 GU toxicity remained in approximately one-sixth of the participants from 4 through 18 months. Grade 1 gastrointestinal (GI) toxicity was reported in 8 individuals during radiotherapy which was resolved in 7 individuals within 1 month. Within 2 weeks following SBR, an additional 5 individuals developed grade 1 or 2 GI toxicities. There were no grade 3 or higher GI or GU toxicities reported. These results were compared to historical controls who received SBRT without a spacer. In individuals who received a spacer implant, 88% and 44% reported no GI and GU toxicity 1 month following treatment compared to 21-62% and 9-49% of individuals in the historical control group, respectively.

Payne and colleagues (2021) published a meta-analysis and systematic review assessing the clinical utility of hydrogel spacers placed prior to SBRT in individuals with localized prostate cancer. A total of 11 prospective and retrospective studies were included. Across all studies, the perirectal space in individuals with SpaceOAR ranged from 9.6 to 14.5 mm and the rectal irradiation was 29% to 56% lower in those with SpaceOar compared to no spacer. The authors noted:

Grade ≥ 2 GI toxicity complications were uncommon. In early follow-up, grade 2 GI complications were reported in 7.0% of patients and no early grade 3+ complications were reported. In late follow-up, the corresponding pooled mean rates were 2.3% for grade 2 and 0.3% for grade 3 GI toxicity.

In a 2021 systematic review, Armstrong and associates reported on the association between the hydrogel spacer, SpaceOAR, and prostate cancer outcomes including radiation dosing, toxicity and quality-of-life. Studies which compared SpaceOar to no spacer using any radiotherapy modality were included, with two of the studies involving SBRT. The authors noted that SpaceOAR “decreased the risk of Grade 2+ acute and late gastrointestinal (GI)/rectal and genitourinary (GU) toxicity, with late GI toxicity of 1% vs 6% (p=0.01) and late GU toxicity of 15% vs 32% (p<0.001).”

Hypofractionated Intensity Modulated Radiation Therapy (IMRT)

While conventional fractional radiotherapy has been considered standard therapy, hypofractionated therapy provides potential benefits including therapeutic ratio improvement, resource use, and individual convenience (Dearnaley, 2016). Moderately hypofractionated IMRT has been shown to be similar or non-inferior to conventionally fractionated IMRT. The NCCN notes “Overall, the panel believes that hypofractionated IMRT techniques, which are more convenient for patients, can be considered as an alternative to conventionally fractionated regimens when clinically indicated.” Hypofractionated and ultrafractionated radiotherapy can be associated with higher toxicity rates due to the application of larger biological doses (Armstrong, 2021; Ogita, 2021).

Conventionally Fractionated IMRT

Song and colleagues (2013) reported the results of an industry sponsored prospective pilot clinical trial involving 54 subjects receiving intensity modulated radiation therapy (IMRT) for prostate cancer. All subjects underwent baseline scans and then were injected with SpaceOAR and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The authors reported that use of SpaceOAR resulted in ≥ 7.5 mm prostate-rectal separation in 95.8% of subjects and 95.7% had decreased rectal V70 of ≥ 25%, with a mean reduction of 8.0 Gy. No significant differences were reported in pre-injection and post-injection prostate planning target volume (PTV), or rectal and bladder volumes. Plan conformities were significantly different before versus after injection (p=0.02). Plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. The authors reported that in multiple regression analysis, greater post-injection reduction in V70 was associated with significantly decreased relative post-injection plan conformity. No significant relationships between reduction in V70 and the other characteristics analyzed were reported. The authors concluded that injection of SpaceOAR resulted in dose reductions to the rectum for > 90% of subjects treated. Furthermore, they stated that rectal sparing was statistically significant across a range of 10 to 75 Gy. The study did not address clinical outcomes.

Gastrointestinal and genitourinary toxicity were recorded during treatment for up to 12 months in 52 subjects in whom the SpaceOAR system was injected prior to IMRT radiotherapy to a dose of 78 Gy (Uhl, 2014). Of the subjects treated, 39.6% and 12.5% experienced acute Grade 1 and Grade 2 gastrointestinal (GI) toxicity using the RTOG/EORTC (Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer) criteria, respectively. No Grade 3 or Grade 4 acute GI toxicity was reported. Only 4.3% of subjects showed late Grade 1 GI toxicity, and there was no late Grade 2 or greater GI toxicity experienced in the study. A total of 41.7%, 35.4% and 2.1% of subjects experienced acute Grade 1, Grade 2 and Grade 3 genitourinary (GU) toxicity, respectively. There was no Grade 4 acute GU toxicity experienced in the study. Late Grade 1 and Grade 2 GU toxicity was experienced in 17.0% and 2.1% of subjects, respectively and no late Grade 3 or greater GU toxicity was reported. Vienna Rectoscopy Scale (VRS) score of 0 was reported for 71% of subjects, and 1 subject (2%) had Grade 3 telangiectasia. No evidence of ulceration, stricture or necrosis was noted at 12 months. The study did not include a control arm for comparison.

The largest published peer-reviewed study involving the use of the SpaceOAR device was reported by Mariados and colleagues (2015). This pivotal manufacturer sponsored, prospective, multicenter, single-blind, randomized, controlled trial (RCT) involved 222 subjects with clinical stage T1 or T2 prostate cancer who were randomized in a 2:1 fashion to receive image-guided IMRT (79.2 Gy in 1.8-Gy fractions) either with (n=149) or without (n=73) placement of the SpaceOAR system and were followed for 15 months. Individuals with extracapsular extension were excluded from the study, the authors cited the theoretical risk of pushing posterior extracapsular disease farther from the prostate during RT. The authors reported that perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. Neither group reported any device-related adverse events, rectal perforations, serious bleeding, or infections. The use of SpaceOAR was reported to have resulted in significant reduction in mean rectal V70 when comparing treatment plans with and without the device in place (12.4% to 3.3%, p<0.0001). Acute rectal adverse event rates were similar between groups, with the exception that significantly fewer spacer group subjects reported experiencing rectal pain. Significant benefits were reported in the spacer group with regard to late (3-15 months) rectal toxicity severity, with a 2.0% and 7.0% late grade 1 rectal toxicity incidence in the spacer and control groups, respectively and no late rectal toxicity greater than grade 1 in the spacer group. At 15 months, 11.6% and 21.4% of spacer and control subjects, respectively, experienced 10-point declines in bowel quality of life. The quality of these results is limited by blinding concerns, there was no physician masking and no evaluation of reliability of the participant masking. The most significant concern is that the study did not meet its primary clinical safety endpoint (Hall, 2021).

In 2017, this same group reported the results of an extension study involving 46 control group subjects and 94 SpaceOAR subjects (63% of the original cohort reported at 15 months for both groups) (Hamstra, 2017). No significant differences were reported for the mean follow-up times between groups. With regard to the volume of the rectum treated to all volumes of V50 to V80, the SpaceOAR group received a significantly smaller volume. For V50 a 54% relative reduction was found, 21% for controls versus 10% for SpaceOAR subjects. The relative reduction at V70 was 79% (10% versus 2%, respectively) and at V80 96% (4% versus 0.1%, respectively). No dosimetry differences were reported for the bladder, bladder wall or bladder/bladder wall within 1 or 2 cm of the prostate. The 3-year incidence of grade ≥ 1 rectal toxicity  (9.2% versus 2.0%) and grade ≥ 2 rectal toxicity (5.7% versus  0%) were significantly lower in the SpaceOAR group versus control group. The rate of grade ≥ 1 urinary incontinence was also significantly lower in the SpaceOAR group (15% versus 4%), but no difference in grade ≥ 2 urinary toxicity was found (7% versus 7%). While there was a genitourinary toxicity improvement in the spacer group, there were no differences in the radiotherapy doses given to the urinary structures between the groups. The authors provide no explanation for this result, raising concerns this finding could be spurious (Hall, 2021).

In 2018, Hamstra and associates reported on the results of a secondary analysis regarding the sexual quality of life in those individuals who participated in the 2015 Mariados RCT. Prior analyses had shown that while there was lower penile bulb radiation dose with spacer use, there was no difference in average sexual quality of life (QOL) between the spacer and control arms. The authors of the analysis noted that the impact of the spacer on sexual function may have been masked as nearly 60% of the participants had moderate to severe sexual dysfunction at baseline. Approximately 41% (88/222) of men were categorized as having adequate sexual QOL at baseline. When comparing individuals with better baseline sexual QOL scores, the spacer arm reported higher overall sexual scores (spacer 58 [± 24.1] versus the control arm 45 [± 24.4]). These results did not reach statistical significance, but did reach threshold minimally clinically important difference (MID). At 3 years, more men in the spacer group versus the control group self-reported “erections sufficient for intercourse" (control 37.5% versus spacer 66.7%), however that difference was not statistically significant.

Pinkawa and colleagues (2017a) published the results of a prospective cohort study of 167 subjects with prostate cancer treated with SpaceOAR and either IMRT or volumetric-modulated arc therapy (VMAT). The subjects were asked to complete the Expanded Prostate Cancer Index Composite (EPIC) QOL questionnaire at 2 months post-treatment and then at a median of 17 months. The authors noted that the SpaceOAR group received a significantly higher dose of radiation to the planning target volume compared to the control group. At the last data collection point (> 12 months) treatment of bowel symptoms and endoscopic examinations were significantly lower in the SpaceOAR group compared to the control group (0% versus 11% and 3% versus 19%; respectively). No differences in acute toxicity were reported. In the SpaceOAR group, mean bowel function scores did not change significantly, whereas control subjects reported a mean decrease of greater than 5 points at 1 year after radiation therapy (RT) compared to baseline. A change of 5-10 points is defined as “little” change in quality of life. The decision to place a spacer was made by the physician and the individual, which could result in a selection bias within the study group. Randomized studies with longer follow-up are needed to further evaluate any potential benefits.

Fischer-Valuck (2017) published the results of a prospective cohort study of 149 subjects undergoing radiotherapy with SpaceOAR. The authors’ investigation was focused on the correlation of spacer symmetry with rectal dose reduction, as well as rectal wall infiltration to acute and late toxicity. They reported that SpaceOAR was symmetrically placed at midline for 71 (47.7%) subjects at the prostate mid-gland as well as 1 cm superior and inferior to mid-gland. The remaining 78 (50.9%) subjects had some level of asymmetry. However, only 2 (1.3%) had far lateral distribution > 2 cm. It was noted that as SpaceOAR placement became more asymmetric, the level of rectal dose reduction relative to their control plans decreased. However, all but the most asymmetrical 1.3% of subjects had significant rectal dose reduction. Rectal wall infiltration with SpaceOAR was reported in 9 (6.0%) subjects. No correlation between rectal wall infiltration and procedure-related adverse events or acute/late rectal toxicity was reported.

In an industry supported systematic review and meta-analysis, Miller and associates (2020) evaluated the association between perirectal spacer use during radiotherapy and clinical outcomes. The study included seven studies which involved 486 individuals who received a hydrogel spacer and 525 controls. The control group was comprised of potential participants who were not eligible for spacer application due to contraindications or comorbidities. The analysis also included data from a study comparing the effectiveness of a hydrogel spacer to balloon spacers. There was no difference between the groups in regards to risk of early grade 2 or higher rectal toxic effects or in changes in bowel-related QOL at 3 months. The hydrogel spacer group was associated with a 77% reduction in grade 2 or higher risk of late rectal toxic effects and a lower risk of rectal toxic effects of any severity at any point in time. The hydrogel group also reported a higher bowel-related QOL in late follow-up, however, this comparison included data from only two studies.

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for prostate cancer (V 3.2022) includes radiation therapy general principles, noting:

Ideally, the accuracy of treatment should be verified by daily prostate localization with any of the following: techniques of IGRT using CT, ultrasound, implanted feducials, or electromagnetic targeting/tracking. Endorectal balloons may be used to improve prostate immobilization. Biocompatible and biodegradable perirectal spacer materials may be implanted between the prostate and rectum in patients undergoing external radiotherapy with organ-confined prostate cancer in order to displace the rectum from high radiation dose regions. A randomized phase III trial demonstrated reduced rectal bleeding in patients undergoing the procedure compared to controls. Retrospective data also support its use in similar patients undergoing brachytherapy. Patients with obvious rectal invasion or visible T3 and posterior extension should not undergo perirectal spacer implantation.”

The NCCN panel also notes that spacer implantation may be associated with rare complications such as rectum perforation and urethral damage.

Summary

There are multiple prospective studies addressing the use of SpaceOAR and showing reduced radiation exposure and rectal and GI toxicities (Chao, 2018; Chao, 2019a; Chao, 2019b; Hedrick, 2017a and 2017b; Juneja, 2015; Pinkawa, 2011; Pinkawa, 2017b; Ruggieri, 2015; Schörghofer, 2019; Te Velde, 2019; van Gysen, 2014; Whalley, 2016; Wilton, 2017; Wu, 2018). There are limited prospective, randomized controlled studies with medium- to long-term follow-up which focus on patient-oriented outcomes. Hall and associate (2021) note:

Prostate cancer is highly curable with both surgery and radiotherapy and, even without SpaceOAR, is associated with an exceedingly low rate of adverse events requiring intervention. Critical reflection and careful consideration of the need, toxicity, and benefits of SpaceOAR are appropriate before the device is recommended for routine care.

Hypofractionated radiation therapy and stereotactic body radiotherapy are intensive RT regimens associated with substantially increased risk for GI and GU side effects (Payne, 2021; Schörghofer, 2019). Perirectal spacers have been shown to reduce radiation doses to the colon and use of perirectal spacers are generally accepted within the medical community in select situations to mitigate the effects of radiation exposure.

In a retrospective analysis of 403 individuals who received conventional or moderate hypofractionation, Schörghofer and colleagues (2019) reported on the complication and toxicity rate of individuals with prostate cancer who received either a gel or balloon spacer. The authors concluded:

In our study we have shown that rectal spacers lead to an increased rate of grade 3 toxicities of 1.24–1.49%. Whether this can be accepted depends on the risk-benefit relation of the used fractionation scheme. When applied in modern IGRT-IMRT based technique, normo- as well as moderately hypofractionated regimens with  biologically equivalent doses of approximately 78Gy are unlikely to cause any CTC [common toxicity criteria] grade 3 (corresponding to RTOG grade 4) or worse toxicities. The benefit of a spacer application in such regimens is questionable since the reduction in radiation induced grade 1 and 2 toxicity may come at the price of increased grade 3 toxicity inflicted by the spacer. However, in highly dose escalated regimens with EQD2 [equivalent dose in 2Gy per fraction] of >80Gy and in stereotactic treatments where even higher BEDs [biologically equivalent doses] are used, the benefit of the spacer becomes more likely to outweigh its risks.

Brachytherapy

Brachytherapy, the placement of radioactive seed implants into prostate tissue, is divided into low-dose-rate (LDR) and high-dose-rate (HDR) therapy. In LDR brachytherapy, the radioactive seeds are permanently implanted into the prostate. Excessive irradiation of the bladder and rectum is avoided as the radiation emitted from these low energy seeds have a short range. In HDR brachytherapy, radioactive seeds are temporarily implanted (NCCN, 2022).

Butler and colleagues (2021) retrospectively compared prostate and rectal dosimetry in individuals who received a hydrogel spacer prior to prostate cancer treatment (n=174) with individuals who did not receive hydrogel spacer prior to prostate cancer treatment (n=174). Of the individuals who received the spacer, a subset received the spacer immediately following LDR brachytherapy (n=91), the remainder of the group had the spacer placed prior to a moderate dose of EBRT followed by LDR brachytherapy (n=83). The rectal mean dose, rectal maximum dose, and rectal wall V50 were significantly lower at post-implant dosimetry in those who received a spacer. There was no significant difference in rectal dosimetry between the groups who received a spacer at different time points. While some parameters were significantly lower in individuals who received a spacer prior to any radiation therapy, the clinical significance of this is unknown. This study did not evaluate any clinical outcomes which might be associated with the use of a hydrogel spacer.

In 2020, Nehlsen and associates, compared the rectal dosimetry, QOL and rectal toxicity outcomes of individuals with intermediate-risk and high-risk prostate cancer who had (n=22) and had not (n=146) received hydrogel spacers prior to combination EBRT and LDR brachytherapy. Follow-up evaluations began 2 months postimplant dosimetry (PID) and continued every 3 months through 2 years. From 2-5 years, 6 month follow-up evaluations were performed. Rectal toxicity was evaluated based on the presence of rectal bleeding at each visit. The median follow-up was longer in the no-spacer group compared to the spacer group (24 months versus 9 months respectively). Baseline and at least one set of follow-up data were available for only 102 participants. There was a significant reduction in the V100rectum in the spacer group compared to the no spacer group. There was also no significant difference in QOL between the groups. There was no significant reduction in overall Grade 1+ rectal toxicity events. There were a number of limitations associated with this study including the retrospective design, insufficient sample size to draw definitive conclusions, limited assessment of toxicities, and a significant drop-out rate.

Kahn and colleagues (2020) evaluated the dosimetric impact and toxicity levels associated with a bioabsorbable hydrogel rectal spacer injected during low-dose-rate (LDR) prostate brachytherapy. Individuals undergoing LDR for prostate cancer received concurrent hydrogel spacer implantation (n=40) and were compared to individuals who did not have a hydrogel spacer implanted (n=40). Individuals with intermediate- and high-risk prostate cancer were eligible to receive EBRT at their physician’s discretion. The average distance between the prostate and rectum with the addition was significantly increased in the spacer group (13.9mm) compared to the control group (6.5mm). At 1 month post-procedure, the rectal grade 1 toxicity was 12.5% in the hydrogel group and 17.5% in the control group. At 1 and 2 years, there was no difference in rectal toxicities between the groups. The authors note that the clinical benefit of hydrogel spacer use during LDR therapy is not clear at a time when the careful placement of permanently implanted seeds is guided by modern ultrasound and treatment planning.

The effect of hydrogel spacers on rectal dosimetric and toxicity outcomes in individuals with intermediate- and high-risk prostate cancer who underwent combined HDR brachytherapy and EBRT was assessed in a retrospective study (Chao, 2019b). Individuals who had received hydrogel spacers (n=32) and individuals who had not received hydrogel spacers (n=65) were included. Therapy consisted of HDR brachytherapy followed by EBRT, with the hydrogel spacer injected at the time of fiducial marker placement. There were no reported post-operative complications. Individuals were evaluated at baseline, every week during EBRT, every 3 months in the first year and every 6 months from years 1 through 5. The median follow-up time for the spacer group was 42 months and 65 months for the control group. Individuals in the spacer group had significantly reduced rectal irradiation compared to the control group. The results on toxicity outcomes were mixed. While the spacer group reported less GI toxicities, there were no significant differences in GU toxicities between the groups.

In 2018, a retrospective review by Taggar and associates reported on the impact of rectal hydrogel spacers on dosimetry and acute rectal toxicity in LDR brachytherapy. Individuals who had a spacer placed immediately following Pd-103 seed-implantation (n=74) were compared to a cohort of individuals who did not receive a spacer (n=136). The spacer cohort included those who received brachytherapy as a monotherapy (initial or salvage) or in combination with EBRT. Implantation of the spacer resulted in a median 11.2 mm distance between the prostate and the rectum. There was a significant improvement in all rectal dosimetric parameters in the spacer group compared to the control group. Acute GI toxicities were reported in 10.8% (8/74) of the spacer group compared to 13.2% (18/136) of the control group. At the first post-treatment follow-up, 7 individuals in the spacer group reported grade 1 rectal toxicity. The small retrospective review of a heterogeneous population represents the experience of a limited number of researchers.

The published studies evaluating the use of hydrogel spacers in individuals undergoing LDR or HDR brachytherapy are limited to retrospective studies. The studies are limited by the retrospective design of all studies, short follow-up times and the heterogeneous population (Beydoun, 2013; Kubo, 2021; Strom, 2014; Vaggers, 2021; Yeh, 2016). These studies are not designed to evaluate the clinical, patient-oriented benefits of spacers in the population undergoing brachytherapy to treat prostate cancer. Unlike the evidence regarding perirectal spacers and external radiotherapy, the current evidence regarding the benefit of perirectal spacers used prior to or in conjunction with brachytherapy is inconclusive..

Other Products

Other products have been investigated for the same indication as SpaceOAR. One such product is DuraSeal® (Integra Lifesciences Corp., Princeton, NJ), a polyethylene glycol hydrogel which received FDA approval in 2005 as an adjunct to sutured dural repair during spinal surgery. A few studies have been published addressing the use of DuraSeal during prostate radiotherapy.

Strom (2014) reported on a nonrandomized controlled trial involving 200 subjects with clinically localized prostate cancer who received high-dose rate brachytherapy with or without intensity modulated radiation therapy. Subjects received treatment either with (n=100) or without (n=100) insertion of DuraSeal into the anterior perirectal fat between the prostate and rectum. The authors reported a DuraSeal implantation success rate of 100%. They also reported that implantation of DuraSeal significantly increased the prostate-rectal separation (12 ± 4 mm with versus 4 ± 2 mm without DuraSeal) and significantly decreased the mean rectal D2 mL (47 ± 9% with versus 60 ± 8% without DuraSeal). It was noted that implantation of DuraSeal decreased rectal doses regardless of body mass index (BMI). Subjects were followed for a median of 8.7 months. No data were presented regarding adverse events, including rectal toxicity.

In 2016, another study was published addressing the use of DuraSeal (Yeh, 2016). This non-controlled case series study involved 326 subjects with prostate carcinoma who underwent combination high-dose rate brachytherapy and external beam radiotherapy. All subjects had DuraSeal implanted into the anterior perirectal fat space prior to radiotherapy. The median follow-up was 16 months. The authors stated that the mean anterior-posterior separation achieved was 1.6 cm (standard deviation [SD] =0.4 cm). Rates of acute Grade 1 and 2 rectal toxicity were 37.4% and 2.8%, respectively. No acute Grade 3/4 toxicities were reported. Rates of late Grade 1, 2, and 3 rectal toxicity were 12.7%, 1.4%, and 0.7%, respectively. There were no late Grade 4 toxicities. The limitations of this study included its single arm, retrospective design and short-term follow-up.

A small nonrandomized controlled trial involving 20 subjects undergoing proton beam therapy with (n=12) or without (n=8) DuraSeal was published by Chung in 2016. However, this small study provides little generalizable information regarding the efficacy of this product.

Another product, Rectafix™ (Scanflex Medical AB), has been studied for the same indications as SpaceOAR. Wilton (2017) described a retrospective study of 45 subjects from the PROMETHEUS trial who received a total dose (TD) of 19 or 20 Gy in two fractions followed by 46 Gy in 23 fractions. This study compared the use of Rectafix (n=35) versus SpaceOAR (n=10). Based on the results of several subanalyses, the authors reported that Rectafix versus SpaceOAR demonstrated lower mean doses at 9 out of 11 measured intervals (p=0.0012). However, they noted that although dose levels were in favor of Rectafix, in absolute terms the differences were small (2.6-9.0%). The findings of this study are weak due to the small subject pool, and retrospective methodology. Further large, well-designed studies are warranted to investigate the safety and efficacy of this product.

Background/Overview

Prostate cancer is the most common cancer among U.S. males. In 2022, an estimated 268,490 new cases of prostate cancer will be diagnosed and approximately 34,500 deaths will be from prostate cancer. More than 3.1 million men are living with a diagnosis of prostate cancer (ACS, 2022).

Radiotherapy for the treatment of prostate cancer is very common, being one of the most used treatment methods available, supported by national guidelines from an array of authoritative organizations. The use of highly conformal radiation techniques allows precise treatment of the prostate while minimizing exposure of adjacent tissue. However, due to the close proximity of surrounding organs, the risk of radiation induced toxicity of the tissue adjacent to the prostate remains. The risk of unintentional exposure can be reduced by daily prostate localization to improve treatment accuracy or by creating a buffer space between the prostate and the rectum to move the rectum away from the treatment field.

On July 19, 2019, the SpaceOAR system was FDA cleared for use during radiotherapy for prostate cancer. SpaceOAR is a biodegradable polyethylene glycol (PEG) hydrogel that is injected as a liquid between the prostate and rectum under ultrasound guidance. Once injected, the liquid solidifies within seconds into a hydrogel that pushes the anterior rectal wall away from the prostate, increasing the peri-rectal space. SpaceOAR is completely resorbed by the body over time. This is in contrast to endorecal balloons or rectal retractors. These devices are used to fix the rectal volume and position, which expands the rectal wall and results in a smaller planning target volume, ultimately sparing more portions of the wall (Ghaffari, 2020). The use of these devices is based on the assumption that the normal rectal parenchyma’s tolerance to radiotherapy is not compromised by the placement of a foreign body in rectum (Hall, 2021).

Radiotherapy doses are based upon the presumed relative sensitivity of malignant and normal tissue (Benjamin, 2017). Radiation doses are divided into 3 categories. Conventional fractionation has a radiation dosage size of 1.8 to 2 Gy (180 to 200 cGy). Moderate hypofractionation is defined as radiation therapy with a dosage size of approximately 2.4 to 4 Gy (240 cGy to 400 cGy). Ultra or extreme hypofractionation, also referred to as SBRT or stereotactic ablative body radiation therapy can be defined as a radiation dosage size of greater than approximately 5 Gy (500 cGy) (Armstrong, 2021; Morgan, 2018; NCCN, 2022). Radiation dosages are administered on a gradient the definitions of conventional, moderate and ultra-fractionation may overlap. Hypofractionation is more clearly defined as therapy delivered in 28 or fewer fractions (NCCN, V3.2022). 

Definitions

FDA Cleared Device: A medical device which the FDA has determined to be substantially equal to another legally marketed device. Once the FDA has approved a device, a 510(k) approval is given.

Fractionation: The division of the total dose of radiation into separate doses or treatments.

High-Dose Rate (HDR) Brachytherapy: A type of radiation therapy in which radioactive material is placed directly into the tumor or surrounding tissue. The radioactive material is left in place for short periods of time, typically a few minutes. 

Hypofractionated Radiation Therapy: Therapy in which the total dose of radiation is divided into larger doses compared to standard radiation doses, resulting in a shorter treatment period.

Low-Dose Rate (LDR) Brachytherapy: A type of radiation therapy in which radioactive material is placed directly into the tumor or surrounding tissue. The radioactive material is left in place for longer periods of time, typically hours or days.

Stereotactic Body Radiation Therapy: External radiation treatment  in which the total radiation dose is divided into small doses and delivered precisely into the tumors, sparing the surrounding tissue. Also known as SABR, SBRT or stereotactic ablative body radiation therapy.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

CPT

 

55874

Transperineal placement of biodegradable material, peri-prostatic, single or multiple injection(s), including image guidance, when performed

 

 

ICD-10 Diagnosis

 

 

Malignant neoplasm of prostate

D07.5

Carcinoma in situ of prostate

Z51.0

Encounter for antineoplastic radiation therapy

Z85.46

Personal history of malignant neoplasm of prostate

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, or for all other diagnoses not listed.

References

Peer Reviewed Publications:

  1. Armstrong N, Bahl A, Pinkawa M, et al. SpaceOAR hydrogel spacer for reducing radiation toxicity during radiotherapy for prostate cancer. A systematic review. Urology. 2021; 156:e74-e85.
  2. Benjamin LC, Tree AC, Dearnaley DP. The role of hypofractionated radiotherapy in prostate cancer. Curr Oncol Rep. 2017; 19(4):30.
  3. Beydoun N, Bucci JA, Chin YS, et al. First report of transperineal polyethylene glycol hydrogel spacer use to curtail rectal radiation dose after permanent iodine-125 prostate brachytherapy. Brachytherapy. 2013; 12(4):368-74.
  4. Butler WM, Kurko BS, Scholl WJ, Merrick GS. Effect of the timing of hydrogel spacer placement on prostate and rectal dosimetry of low-dose-rate brachytherapy implants. J Contemp Brachytherapy. 2021; 13(2):145-151.
  5. Chao M, Ho H, Chan Y, et al. Prospective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy. BJU Int. 2018; 122(3):427-433.
  6. Chao M, Lim Joon D, Khoo V, et al. The use of hydrogel spacer in men undergoing high-dose prostate cancer radiotherapy: results of a prospective phase 2 clinical trial. World J Urol. 2019a; 37(6):1111-1116.
  7. Chao M, Ow D, Ho H, et al. Improving rectal dosimetry for patients with intermediate and high-risk prostate cancer undergoing combined high-dose-rate brachytherapy and external beam radiotherapy with hydrogel space. J Contemp Brachytherapy. 2019b; 11(1):8-13.
  8. Chung H, Polf J, Badiyan S, et al. Rectal dose to prostate cancer patients treated with proton therapy with or without rectal spacer. J Appl Clin Med Phys. 2017; 18(1):32-39.
  9. Dearnaley D, Syndikus I, Mossop H, et al; CHHiP Investigators. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2016; 7(8):1047-1060.
  10. Fischer-Valuck BW, Chundury A, Gay H, et al. Hydrogel spacer distribution within the perirectal space in patients undergoing radiotherapy for prostate cancer: impact of spacer symmetry on rectal dose reduction and the clinical consequences of hydrogel infiltration into the rectal wall. Pract Radiat Oncol. 2017; 7(3):195-202.
  11. Ghaffari H, Navaser M, Refahi S. In regard to Cuccia et al.: impact of hydrogel peri-rectal spacer insertion on prostate gland intra-fraction motion during 1.5 T MR-guided stereotactic body radiotherapy. Radiat Oncol. 2020; 15(1):199.
  12. Hall WA, Tree AC, Dearnaley D, et al. Considering benefit and risk before routinely recommending SpaceOAR. Lancet Oncol. 2021; 22(1):11-13.
  13. Hamstra DA, Mariados N, Sylvester J, et al. Continued benefit to rectal separation for prostate radiation therapy: final results of a phase III trial. Int J Radiat Oncol Biol Phys. 2017; 97(5):976-985.
  14. Hamstra DA, Mariados N, Sylvester J, et al. Sexual quality of life following prostate intensity modulated radiation therapy (IMRT) with a rectal/prostate spacer: Secondary analysis of a phase 3 trial. Pract Radiat Oncol. 2018; 8(1):e7-e15.
  15. Hedrick SG, Fagundes M, Case S, et al. Validation of rectal sparing throughout the course of proton therapy treatment in prostate cancer patients treated with SpaceOAR®. J Appl Clin Med Phys. 2017; 18(1):82-89.
  16. Hedrick SG, Fagundes M, Robison B, et al. A comparison between hydrogel spacer and endorectal balloon: an analysis of intrafraction prostate motion during proton therapy. J Appl Clin Med Phys. 2017; 18(2):106-112.
  17. Hwang ME, Mayeda M, Liz M, et al. Stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer: toxicity profile and early oncologic outcomes. Radiat Oncol. 2019; 14(1):136.
  18. Jones RT, Hassan Rezaeian N, Desai NB, et al. Dosimetric comparison of rectal-sparing capabilities of rectal balloon vs injectable spacer gel in stereotactic body radiation therapy for prostate cancer: lessons learned from prospective trials. Med Dosim. 2017. pii: S0958-3947(17)30067-5.
  19. Juneja P, Kneebone A, Booth JT, et al. Prostate motion during radiotherapy of prostate cancer patients with and without application of a hydrogel spacer: a comparative study. Radiat Oncol. 2015; 10:215.
  20. Kahn J, Dahman B, McLaughlin C, et al. Rectal spacing, prostate coverage, and periprocedural outcomes after hydrogel spacer injection during low-dose-rate brachytherapy implantation. Brachytherapy. 2020; 19(2):228-233.
  21. Mariados N, Sylvester J, Shah D, et al. Hydrogel spacer prospective multicenter randomized controlled pivotal trial: dosimetric and clinical effects of perirectal spacer application in men undergoing prostate image guided intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2015; 92(5):971-977.
  22. Miller LE, Efstathiou JA, Bhattacharyya SK, et al. Association of the placement of a perirectal hydrogel spacer with the clinical outcomes of men receiving radiotherapy for prostate cancer: a systematic review and meta-analysis. JAMA Netw Open. 2020; 3(6):e208221.
  23. Nehlsen AD, Sindhu KK, Moshier E, et al. The impact of a rectal hydrogel spacer on dosimetric and toxicity outcomes among patients undergoing combination therapy with external beam radiotherapy and low-dose-rate brachytherapy. Brachytherapy. 2021; 20(2):296-301.
  24. Ogita M, Yamashita H, Nozawa Y, et al. Phase II study of stereotactic body radiotherapy with hydrogel spacer for prostate cancer: acute toxicity and propensity score-matched comparison. Radiat Oncol. 2021; 16(1):107.
  25. Payne HA, Pinkawa M, Peedell C, et al. SpaceOAR hydrogel spacer injection prior to stereotactic body radiation therapy for men with localized prostate cancer: A systematic review. Medicine (Baltimore). 2021; 100(49):e28111.
  26. Pinkawa M, Berneking V, König L, et al. Hydrogel injection reduces rectal toxicity after radiotherapy for localized prostate cancer. Strahlenther Onkol. 2017a; 193(1):22-28.
  27. Pinkawa M, Berneking V, Schlenter M, Krenkel B, Eble MJ. Quality of life After radiation therapy for prostate cancer with a hydrogel spacer: 5-year results. Int J Radiat Oncol Biol Phys. 2017b; 99(2):374-377.
  28. Pinkawa M, Corral NE, Caffaro M, et al. Application of a spacer gel to optimize three-dimensional conformal and intensity modulated radiotherapy for prostate cancer. Radiother Oncol. 2011; 100(3):436-441.
  29. Ruggieri R, Naccarato S, Stavrev P, et al. Volumetric-modulated arc stereotactic body radiotherapy for prostate cancer: dosimetric impact of an increased near-maximum target dose and of a rectal spacer. Br J Radiol. 2015; 88(1054):20140736.
  30. Schörghofer A, Drerup M, Kunit T, et al. Rectum-spacer related acute toxicity - endoscopy results of 403 prostate cancer patients after implantation of gel or balloon spacers. Radiat Oncol. 2019; 14(1):47.
  31. Song DY, Herfarth KK, Uhl M, et al. A multi-institutional clinical trial of rectal dose reduction via injected polyethylene-glycol hydrogel during intensity modulated radiation therapy for prostate cancer: analysis of dosimetric outcomes. Int J Radiat Oncol Biol Phys. 2013; 87(1):81-87.
  32. Strom TJ, Wilder RB, Fernandez DC, et al. A dosimetric study of polyethylene glycol hydrogel in 200 prostate cancer patients treated with high-dose rate brachytherapy±intensity modulated radiation therapy. Radiother Oncol. 2014; 111(1):126-131.
  33. Taggar AS, Charas T, Cohen GN, et al. Placement of an absorbable rectal hydrogel spacer in patients undergoing low-dose-rate brachytherapy with palladium-103. Brachytherapy. 2018; 17(2):251-258.
  34. Uhl M, Herfarth K, Eble MJ, et al. Absorbable hydrogel spacer use in men undergoing prostate cancer radiotherapy: 12 month toxicity and proctoscopy results of a prospective multicenter phase II trial. Radiat Oncol. 2014; 9:96.
  35. Vaggers S, Rai BP, Chedgy ECP, et al. Polyethylene glycol-based hydrogel rectal spacers for prostate brachytherapy: a systematic review with a focus on technique. World J Urol. 2021; 39(6):1769-1780.
  36. van Gysen K, Kneebone A, Alfieri F, et al. Feasibility of and rectal dosimetry improvement with the use of SpaceOAR® hydrogel for dose-escalated prostate cancer radiotherapy. J Med Imaging Radiat Oncol. 2014; 58(4):511-516.
  37. Whalley D, Hruby G, Alfieri F, et al. SpaceOAR hydrogel in dose-escalated prostate cancer radiotherapy: rectal dosimetry and late toxicity. Clin Oncol (R Coll Radiol). 2016; 28(10):e148-154.
  38. Wilton L, Richardson M, Keats S, et al. Rectal protection in prostate stereotactic radiotherapy: a retrospective exploratory analysis of two rectal displacement devices. J Med Radiat Sci. 2017; 64(4):266-273.
  39. Wu SY, Boreta L, Wu A, et al. Improved rectal dosimetry with the use of SpaceOAR during high-dose-rate brachytherapy. Brachytherapy. 2018; 17(2):259-264.
  40. Yeh J, Lehrich B, Tran C, et al. Polyethylene glycol hydrogel rectal spacer implantation in patients with prostate cancer undergoing combination high-dose-rate brachytherapy and external beam radiotherapy. Brachytherapy. 2016; 15(3):283-287.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Cancer Society (ACS). Key Statistics from Prostate Cancer. January 12, 2022. Available at: https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed on March 11, 2022.
  2. Canadian Agency for Drugs and Technologies in Health (CADTH). Hydrogel Spacers for Patients with Prostate Cancer: A Review of Clinical Effectiveness and Cost Effectiveness. February 22, 2019. Available at: https://www.cadth.ca/sites/default/files/pdf/htis/2019/RC1069%20Space%20OAR%20Hydrogel%20Final.pdf. Accessed on March 11, 2022.
  3. Lawrie TA, Green JT, Beresford M, et al. Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers. Cochrane Database Syst Rev. 2018; 1:CD012529.\
  4. Morgan SC, Hoffman K, Loblaw DA, et al. Hypofractionated radiation therapy for localized prostate cancer: An ASTRO, ASCO, and AUA evidence-based guideline. J Clin Oncol. 2018; 36(34):JCO1801097.
  5. NCCN Clinical Practice Guidelines in Oncology™ (NCCN). © 2022 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website at: http://www.nccn.org/index.asp. Accessed on March 11, 2022.
  6. U.S. Food and Drug Administration (FDA) 510(k) Premarket Notification Database. Summary of Safety and Effectiveness. Rockville, MD: FDA. SpaceOAR Vue Hydrogel. K182971. July 17, 2019. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf18/K182971.pdf. Accessed on March 11, 2022.
Index

DuraSeal
Rectafix
SpaceOAR

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Revised

05/12/2022

Medical Policy & Technology Assessment Committee (MPTAC) review. Revised medically necessary position statement to clarify criteria without a change in intent. Updated Rationale, Background, Definitions and References sections.

Revised

05/13/2021

MPTAC review. Revised position statement from perirectal spacers are investigational and not medically necessary in all cases to statement that perirectal spacers are medical necessary for hypofractionated radiation therapy or stereotactic body radiotherapy when criteria are met. Added investigational and not medically necessary statement when criteria are not met and for all other indications. Updated Rationale, Coding and References sections.

Reviewed

02/11/2021

MPTAC review. Updated Rationale, Background, References and Description sections.

Reviewed

02/20/2020

MPTAC review. Updated Rationale, Background, References and Description sections.

Reviewed

06/06/2019

MPTAC review. Updated Rationale and References sections.

Reviewed

07/26/2018

MPTAC review.

Reviewed

07/18/2018

Hematology/Oncology Subcommittee review. Updated Rationale and References sections.

Reviewed

11/02/2017

MPTAC review.

Reviewed

11/01/2017

Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Rationale and References sections. Updated Coding section with 01/01/2018 CPT changes; removed 0438T deleted 12/31/2017.

Revised

11/03/2016

MPTAC review.

Revised

11/02/2016

Hematology/Oncology Subcommittee review. Revised title. Clarified MN statement. Updated Rationale and Reference sections.

New

05/05/2016

MPTAC review.

New

05/04/2016

Hematology/Oncology Subcommittee review. Initial document development.

 


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