Latest Review Date: July 2024

Category: Medical

POLICY:

Effective for dates of service on and after November 15, 2019:

Hydrogel spacer use during radiotherapy for prostate cancer is considered medically necessary when the following criteria are met:

• Prostate cancer that is considered low or favorable intermediate risk
• Tumor is confined to prostate
• PSA <20
• Gleason score ≤7
• Prostate volume <80cm3
• No prior hormone therapy or surgery or radiation of the prostate
• No active bleeding disorder
• Patient will be treated with a radiation source other than hadron or proton therapy

Hydrogel spacers are considered investigational in all other situations.

DESCRIPTION OF PROCEDURE OR SERVICE:

For low or intermediate risk prostate cancer, radiation therapy is an option. Because the rectum lies in close proximity to the prostate, the risk of rectal toxicity is high. One approach is to push the rectum away from the prostate, increasing the space between the two and reducing the radiation dose to the rectum. A variety of biomaterials, including polyethylene glycol hydrogels (e.g., SpaceOAR™ System), hyaluronic acid hydrogels (Barrigel Injectable Gel), or absorbable balloon implants (BioProtect Balloon Implant™ System), have been evaluated as perirectal spacers.

Prostate cancer is a complex, heterogeneous disease, ranging from microscopic tumors unlikely to be life-threatening to aggressive tumors that can metastasize, leading to morbidity or death. It is the second most common cancer in men, with approximately one in eight men diagnosed with prostate cancer over their lifetime. Cancer is typically suspected due to increased levels of prostate-specific antigen upon screening. A digital rectal exam may detect nodules, induration, or asymmetry, and followed by an ultrasound-guided biopsy with evaluation of the number and grade of positive biopsy cores.

Clinical staging is based on the digital rectal exam and biopsy results. T1 lesions are not palpable while T2 lesions are palpable but appear to be confined to the prostate. T3 lesions extend through the prostatic capsule, and T4 lesions are fixed to or invade adjacent structures. The most widely used grading scheme for a prostate biopsy is the Gleason system. It is an architectural grading system ranging from 1 (well differentiated) to 5 (poorly differentiated); the score is the sum of the primary and secondary patterns. A Gleason score of 6 or less is low-grade prostate cancer that usually grows slowly; 7 is an intermediate grade; 8 to 10 is high-grade cancer that grows more quickly. A revised prostate cancer grading system has been adopted by the National Cancer Institute and the World Health Organization. A cross-walk of these grading systems is shown in Table 1.

Table 1. Prostate Cancer Grading Systems

Treatment

Early localized disease can usually be treated with surgery and radiotherapy, although active surveillance may be adopted in men whose cancer is unlikely to cause major health problems during their lifespan or for whom the treatment might be dangerous. In patients with inoperable or metastatic disease, treatment consists of hormonal therapy and possibly chemotherapy. Treatment decisions are based on the anatomic extent of the lesion, the histologic grade from biopsy, and serum prostate-specific antigen (PSA) level. Other factors in treatment decisions are expected outcomes, potential complications, along with medical condition, age, comorbidities, and personal preferences. For patients with clinically localized low-risk cancer (no palpable tumor and PSA of ten or less), active surveillance is an option. Definitive therapy with radical prostatectomy or radiation therapy (RT) with external beam and/or brachytherapy is also an option for low or intermediate risk disease. Dose escalation of RT improves cancer outcomes but also increases the risk of urinary or bowel toxicity. Image-guided RT and intensity-modulated RT may be used to limit margins and reduce toxicity but because the rectum lies in close proximity to the prostate, the risk of rectal toxicity remains high. Hypofractionation, dose escalation, and salvage RT protocols can be particularly prone to rectal toxicity.

Perirectal Spacers

One approach to the problem of rectal toxicity is to push the rectum away from the prostate, increasing the space between the two organs and reducing the radiation dose to the anterior rectal wall. A variety of biomaterials, including collagen, polyethylene glycol (PEG) hydrogels, hyaluronic acid (HA) hydrogels and absorbable balloons have been evaluated as a means to reduce rectal radiation exposure. The SpaceOAR System is the first PEG hydrogel that was cleared by the U.S Food and Drug Administration (FDA) specifically for use during RT of the prostate. Subsequently, Barrigel Injectable Gel, an HA hydrogel, and BioProtect Balloon Implant, an absorbable balloon hydrogel spacer, were FDA-approved in 2022 and 2023, respectively. The chemical composition of the SpaceOAR is similar to a PEG-based hydrogel that is Food and Drug Administration approved as a dural sealant. Hydrodissection is achieved with saline between the retroprostatic (Denonvilliers’) fascia and the anterior rectal wall using a transperineal approach. Once the needle placement is confirmed, two solutions in a two-channel syringe are injected into the perirectal space. The hydrogel then polymerizes to form a soft mass. The hydrogel maintains the space for approximately 3 months, the duration of radiotherapy, and is completely absorbed by 12 months. The PEG hydrogel may be injected at the same time as the placement of fiducial markers in the prostate.

KEY POINTS:

The literature search was conducted through May 22, 2024.

Summary of Evidence

For individuals who have prostate cancer and are undergoing radiation therapy who receive a hydrogel spacer, the evidence includes a pivotal randomized controlled trial (RCT) with a 3-year follow-up for the SpaceOAR system, a pivotal RCT with up to 6-month follow-up for the Barrigel, observational studies, and systematic reviews of these studies. Relevant outcomes include symptoms, quality of life, and treatment-related morbidity. The combined evidence indicates that the hydrogel spacer can reduce the radiation dose to the rectum with a statistically significant decrease in Grade 1 or greater late toxicity with a number needed to treat (NNT) of 14.3. There were few events of greater than Grade 1 toxicity in either group across all trials, and the NNT for a reduction in clinically significant Grade 2 toxicity has been reported as 68 for SpaceOar. Patient-reported declines in rectal and urinary quality of life at 3 years in the SpaceOar studies were statistically lower in the spacer group and met the threshold for a clinically significant difference, although patients were not blinded to treatment at the longer-term follow-up. The NNT for late improvement in rectal and urinary quality of life was 6.3 to 6.7, respectively, for SpaceOar analysis. Limitations to all RCTs include the lack of blinding and the exclusion of patients who might be at greater risk of rectal toxicity. Evidence from observational studies is inconclusive but generally shows a decrease in radiation dose to the rectum with the insertion of a hydrogel spacer. However, the potential benefits of the hydrogel spacer must be balanced against the risks of an additional procedure. Additional studies are needed to corroborate the findings of the pivotal RCTs, to identify the factors that increase the risk of rectal toxicity, and to determine who is likely to benefit from the use of a spacer. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network

The National Comprehensive Cancer Network for prostate cancer (v4.2024) provides the following recommendation in principles of radiation therapy (PROS-F), "Overall, the panel believes that 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."

“Perirectal spacer materials may be employed when the previously mentioned techniques [highly conformal RT, photon or proton beam, brachytherapy boost] are insufficient to improve oncologic cure rates and/or reduce side effects due to anatomic geometry or other patient-related factors, such as medication usage and/or comorbid conditions. Patients with obvious rectal invasion or visible T3 and posterior extension should not undergo perirectal spacer implantation.”

National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence (NICE) (2023) updated their guidance on the biodegradable spacer. The NICE recommendations state that “Evidence on the safety and efficacy of biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer is limited in quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research."

American Society of Clinical Oncology, the American Urological Association, and the American Society for Radiation Oncology

The American Society of Clinical Oncology, the American Urological Association, and the American Society for Radiation Oncology (2018) published a joint guideline on hypofractionated radiation therapy for localized prostate cancer. The guideline recommends that men be counseled about the small increased risk of acute gastrointestinal (GI) toxicity with hypofractionation. “Moderately fractionated EBRT has a similar risk of acute and late genitourinary and late GI toxicity compared with conventionally fractionated EBRT. However, physicians should discuss the limited follow-up beyond 5 years for most existing RCTs [randomized controlled trials] evaluating moderate hypofractionation.” This was a strong recommendation based on high-quality evidence and 100% consensus. Additionally, the guideline mentions that prostate-rectal spacers can be used to allow rectal dose sparing.

American College of Radiology

American College of Radiology appropriateness criteria, last reviewed in 2016, for dose-volume constraints for the rectum with external beam radiotherapy are described in Table 2.

Table 2. Dose Constraints for the Rectum With External Beam Radiotherapy

EBRT: External beam radiotherapy; Gy: gray

V100= volume of structure (X%) receiving 100% of the dose

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Bulking agent, Polyethylene glycol hydrogel, PEG, Prostate cancer, radiation therapy, rectal protection, Spacing organs at risk, OAR, hydrogel, SpaceOAR, hyaluronic acid hydrogels, Barrigel Injectable Gel, absorbable balloon implants, BioProtect Balloon Implant System.

APPROVED BY GOVERNING BODIES:

In October 2014, SpaceOAR™ (Augmenix, a subsidiary of Boston Scientific) was cleared by the U.S. Food and Drug Administration (FDA) through the De Novo process (DEN140030). Barrigel Injectable Gel (Palette Life Sciences) was approved by the FDA via the premarket approval process in March 2022 (K220641; FDA product code: OVB), followed by BioProtect Balloon Implant™ System (BioProtect, Ltd) in 2023 (K222972; FDA product code: OVB).The intended and approved use of SpaceOAR System, Barrigel, and BioProtect Balloon Implant is to temporarily position the anterior rectal wall away from the prostate during radiotherapy for prostate cancer and in creating this space it is the intent of these hydrogel spacers to reduce the radiation dose delivered to the anterior rectum.”

DuraSeal® Exact (Integra) was approved by the FDA through the premarket approval process as a spine and cranial sealant (dura mater) and has been used off-label as a perirectal spacer.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. 

CURRENT CODING

CPT Codes:

REFERENCES:

1. American Cancer Society. Key Statistics for Prostate Cancer. www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html. 

2. American College of Radiology. ACR appropriateness criteria for external beam radiation therapy treatment planning for clinically localized prostate cancer. 2016. acsearch.acr.org/docs/69396/Narrative/. 

3. Babar M, Katz A, Ciatto M. Dosimetric and clinical outcomes of SpaceOAR in men undergoing external beam radiation therapy for localized prostate cancer: A systematic review. J Med Imaging Radiat Oncol. Jun 2021; 65(3): 384-397.

4. Butler WM, Kurko BS, Scholl WJ, et al. Effect of the timing of hydrogel spacer placement on prostate and rectal dosimetry of low-dose-rate brachytherapy implants. J Contemp Brachytherapy. Apr 2021; 13(2): 145-151.
5. 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. 2019 Feb;11(1)8-13.
6. Fischer-Valuck BW, Chundury A, Gay H, Bosch W, Michalski J. 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. 
7. Forero DF, Almeida N, Dendukuri N. Hydrogel Spacer to reduce rectal toxicity in prostate cancer radiotherapy: a health technology assessment. Report No. 82. April 16, 2018. muhc.ca/sites/default/files/micro/m-TAU/SpaceOAR.pdf. 
8. Gleason DF. Classification of prostatic carcinomas. Cancer Chemother Rep. Mar 1966; 50(3): 125-8.
9. 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. Apr 1 2017;97(5):976-985.
10. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
11. 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. Mar 2020; 19(2): 228-233.
12. Karsh LI, Gross ET, Pieczonka CM, et al. Absorbable hydrogel spacer use in prostate radiotherapy: A comprehensive review of phase 3 clinical published data. Urology. 2018 May; 115:39-44.
13. Mariados NF, Orio PF, Schiffman Z, et al. Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial. JAMA Oncol. Apr 01 2023; 9(4): 511-518.
14. 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. Aug 1 2015;92(5):971-977.
15. McDonald AM, Baker CB, Popple RA, et al. Different rectal toxicity tolerance with and without simultaneous conventionally-fractionated pelvic lymph node treatment in patients receiving hypofractionated prostate radiotherapy.Radiat Oncol. Jun 03 2014; 9: 129.
16. 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. Jun 01 2020; 3(6): e208221.
17. Morgan SC, Hoffman K, Loblaw DA, et al. Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline. J Urol. Oct 9 2018.
18. National Cancer Institute. SEER Database. 2018; seer.cancer.gov/seerinquiry/index.php?page=view&id=20170036&type=q.
19. National Comprehensive Cancer Network NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer v4.2024 www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. 
20. National Institute for Health and Care Excellence. Biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer. IPG752 2023. Available at: www.nice.org.uk/guidance/ipg752/
21. 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. Mar-Apr 2021; 20(2): 296-301.
22. Pinkawa M, Berneking V, Konig L, et al. Hydrogel injection reduces rectal toxicity after radiotherapy for localized prostate cancer. Strahlenther Onkol. 2017 Jan;193(1):22-28.
23. 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. International journal of radiation oncology, biology, physics. 2017;99(2):374-377.
24. Pinkawa M, Piroth MD, Holy R, et al. Quality of life after intensity-modulated radiotherapy for prostate cancer with a hydrogel spacer. Matched-pair analysis. Strahlenther Onkol. 2012 Oct;188(10):917-25.
25. Seymour ZA, Hamstra DA, Daignault-Newton S, et al. Long-term follow-up after radiotherapy for prostate cancer with and without rectal hydrogel spacer: a pooled prospective evaluation of bowel-associated quality of life. BJU Int. Sep 2020; 126(3): 367-372.
26. Skolarus TA, Dunn RL, Sanda MG, et al. Minimally important difference for the Expanded Prostate Cancer Index Composite Short Form. Urology. Jan 2015;85(1):101-105.
27. Te Velde BL, Westhuyzen J, Awad N, et al. Late toxicities of prostate cancer radiotherapy with and without hydrogel SpaceAOR insertion. J Med Imaging Radiat Oncol. 2019 Dec;63(6):836-841.
28. Te Velde BL, Westhuyzen J, Awad N, et al. Can a peri-rectal hydrogel spaceOAR programme for prostate cancer intensity-modulated radiotherapy be successfully implemented in a regional setting? J Med Imaging Radiat Oncol. 2017 Aug;61(4):528-533.
29. 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 Oct;28(10):e148-54. Te Velde BL, Westhuyzen J, Awad N, et al. Can a peri-rectal hydrogel spaceOAR programme for prostate cancer intensity-modulated radiotherapy be successfully implemented in a regional setting? J Med Imaging Radiat Oncol. 2017 Aug;61(4):528-533.

POLICY HISTORY:

Medical Policy Panel, January 2019

Medical Policy Group, February 2019 (4): Adopted new policy; however, spaceoar has been previously considered investigational.

Medical Policy Administration Committee, February 2019

Available for comment February 8, 2019 – March 25, 2019

Medical Policy Group, November 2019 (4):  Updated policy statements to allow coverage for spaceoar with criteria.

Medical Policy Administration Committee: December 2019

Available for Comment: November 15, 2019 – December 30, 2019

Medical Policy Panel, January 2020

Medical Policy Group, January 2020 (5): Updates to Description, Key Points, Approved by Governing Bodies, Practice Guidelines and Position Statements, and References. No change to Policy Statement.

Medical Policy Panel, January 2020

Medical Policy Group, January 2020 (5): Updates to Key Points, Approved by Governing Bodies, Practice Guidelines and Position Statements, and References. No changes to Policy Statement.

Medical Policy Panel, July 2021

Medical Policy Group, July 2021 (5): Updates to Description, Key Points, Practice Guidelines and Position Statements, Approved by Governing Bodies, and References. No change to Policy Statement.

Medical Policy Panel, July 2022

Medical Policy Group, July 2022 (5): Updates to Key Points, Practice Guidelines and Position Statements, and References. No change to Policy Statement.

Medical Policy Panel, July 2023

Medical Policy Group, July 2023 (11): Updates to Description, Key Points, Benefit Application, and References. No change to Policy Statement.

Medical Policy Panel, July 2024

Medical Policy Group, July 2024 (11): Updates to Description, Key Points, Key Words hyaluronic acid hydrogels, Barrigel Injectable Gel, absorbable balloon implants, BioProtect Balloon Implant System added, Approved by Governing Bodies, and References. No change to Policy Statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.