Cost Effectiveness of the Insertion of Hydrogel Spacer in Men Treated With Radiation Therapy for Prostate Cancer

ABSTRACT 

Purpose: The study examined the cost effectiveness of prostate cancer radiotherapy with and without the use of a hydrogel spacer.

Design and Methodology: Retrospective data from Truven Health Analytics’ Commercial Claims and Medicare Supplemental database between 2012 and 2017 identified patients with prostate cancer, their subsequent radiation therapies (intensity modulated radiotherapy, stereotactic body radiotherapy , and brachytherapy), and associated toxicities (gastrointestinal [GI] and genitourinary [GU] toxicities and sexual dysfunction [SD]). Two cost-effectiveness model inputs, gross and adjusted costs per patient, were calculated. Complications and costs were modeled for two scenarios. The first assumed hydrogel spacers reduced GI toxicity but not GU toxicity or SD. The second assumed that hydrogel spacers benefited GI toxicity, GU toxicity, and SD, and showed improvements in GI, GU, and sexual quality of life. The primary output was the cost per additional quality-adjusted life year (QALY) gained by adding a spacer during radiotherapy compared with radiotherapy without a spacer.

Results: Under the first model scenario, the increased per-patient cost of $3,311 achieved an additional 0.1317 QALYs over two years and an overall incremental cost-effectiveness ratio (ICER) of $21,898 per QALY. The second scenario showed an increased per-patient cost of $2,759 and an additional 0.2148 QALYs over two years, with an overall ICER of $12,841 per QALY.

Conclusion: Over a two-year period, hydrogel spacer use during radiation treatment in men with prostate cancer reduced GI, GU, and SD complications and yielded QALY gains at moderately increased costs meeting generally accepted definitions of cost effectiveness.

Keywords: cancer care/oncology, prostate cancer, cost effectiveness/cost analysis, quality of life, radiology

INTRODUCTION

Prostate cancer is the most common cancer among men in the United States. One in nine men will be diagnosed with prostate cancer in their lifetime, with a projected 174,650 new cases diagnosed in 2019 (SEER 2018, Siegel 2019). When treatment is necessary, high-dose radiation is a well-
established method and has results similar to surgery in low-, inter­mediate-, and high-risk cases (Prostate Testing 2016, Kishan 2018, Lennernas 2015). Radiotherapy for prostate cancer is, however, associated with radiation-induced toxicities to the gastrointestinal (GI) and genitourinary (GU) systems and with sexual dysfunction (SD). Potential complications include bleeding, proctitis, incontinence, strictures, fistulas, and erectile dysfunction (Pan 2018). Highly conformal techniques like image-guided radiation therapy can reduce radiation exposure of the rectum, but doses to the rectum can remain high (Zietman 2010).

To allow maximum benefit of radio­therapy while minimizing adverse effects, more space can be created between the prostate and rectum. Several methods of creating this space have been developed, including absorbable hydrogel spacers (HS), hyaluronic acid, collagen, and implantable absorbable balloons (Mahal 2014). Absorbable HS are primarily water when inserted between the rectum and the prostate, where they solidify into a polymer that remains in place for most, if not all, radiation treatments. One such commercially available device (SpaceOAR, Augmenix), a spacer made of a polyethylene glycol hydrogel, increases the perirectal space by an average of over 10 mm and then is completely resorbed by the body within 12 months (Mariados 2015). Studies have shown that placement of the device between the prostate and rectum can optimize radiation therapies for patients with localized prostate cancer, and potentially minimize radiation-induced rectal toxicity and complications (Mariados 2015, Uhl 2014, Susil 2010). Those studies include a phase 3 trial that demonstrated a statistically significant reduction in late rectal toxicity (adverse events affecting the rectum, i.e., rectal bleeding) with the use of the spacer compared with rectal toxicity without spacer use (Mariados 2015).

Previous studies have shown that the spacers are easy to put in place, well tolerated by patients, reduce radiation exposure to the rectum, and are associated with good clinical outcomes. Clinical trials demonstrated substantial reduction of GI and GU toxicities related to radiation therapies with spacer use (Zietman 2010, Mariados 2015, Wolf 2015). Mariados (2015) found that patients with spacers showed fewer Grade II or higher toxicities than those without (GI: 4.1% vs. 0%; GU: 37.8% vs. 6.8%) from base treatment to 15 months. A quality-of-life (QoL) analysis found the use of an HS decreased the dose of the radiation to the penile bulb; this reduced dose was associated with improved erectile function compared with the control group based on patient-reported sexual function (Hamstra 2018). A prospective study by Uhl (2014) found lower rates of rectal side effects compared to other studies. Hamstra (2017) and Karsh (2018) both found that from six months to three years following treatment, patient-reported bowel QoL was near or above baseline in men who used HS, while it was below baseline in men in the control group. Additionally, Karsh found that 2.5% of men treated with radiation with an HS had long-term (at 37 months post-treatment) minimally important declines in bowel, urinary, or sexual QoL, compared with 20% of men in the control group.

Use of a spacer will increase the health care costs of the initial treatment, but reductions in rectal complications and improved QoL may reduce overall costs and improve outcomes and patient experience of care (Hutchinson 2016). Uhl (2014) concluded that the lower rate of late side effects on the rectum from radiation and the potential for enabling hypo­fractionation and dose escalation associated with the use of HS may lead to decreased overall costs for the health care system. Previous studies have compared the cost of rectal complications between patients who do and do not use rectal spacer (Uhl 2014, Vanneste 2015). But to our knowledge, there is only one other overall cost-effectiveness analysis for prostate cancer treatment that compares men who receive the HS with those who do not (Levy 2019). That study, based on a Markov model using inputs derived from the phase 3 pivo­tal trial for the SpaceOAR hydrogel insert, concluded that the spacer is cost effective in hospital outpatient and ambulatory settings but may be affected by the setting where the procedure is performed.

The objective of this study is to compare the overall cost effectiveness of radiation therapy for prostate cancer with and without HS. Cost estimates of treatment complications are based on a real-world analysis of a commercial claims database. If similar results were found using a different methodology, it would provide convergent validity for a conclusion of cost effectiveness.

METHODS

Data source

We obtained real-world data to model HS cost effectiveness across different types of prostate cancer radiotherapy. Retrospective claims data from 2012 to 2017 were obtained from Truven Health Analytics’ Commercial Claims and Medicare Supplemental (CCMS) database. ICD-9, ICD-10, and Current Procedural Terminology (CPT) codes were used to identify patients with prostate cancer who were subsequently treated with radiation therapies including intensity-­modulated radiotherapy (IMRT), stereo­tactic body radiotherapy (SBRT), and brachytherapy. Diagnostic codes were also used to identify GI toxicities, GU toxicities, and SD that can arise as a result of radiation therapies. We included all inpatient and outpatient claims. Appendix 1 lists all codes used to identify diagnostic and treatment procedures for prostate cancer. The index procedure was defined as the first occurrence for a patient of any of the radiotherapy treatment codes in Appendix 1 (all the appendices are available at www.managedcaremag.com/appendix), in conjunction with a diagnosis of malignant neoplasm of the prostate as defined by the associated codes.

The complication and procedure codes were derived through a literature review and qualitative interviews with physicians (Hamstra 2017, Karsh 2018, Hutchinson 2016). Prior to the database analysis, we consulted with two radiation oncologists and one urologist. The consultation detailed the diagnostic and treatment pathways of more than 20 detrimental outcomes of radiation treatment and provided information on related diagnostic exams, pharmacologic interventions, consult requirements, and other information regarding medical resource utilization patterns, to inform an exhaustive coding effort. Appendix 2 lists the 10 most common procedure and complication codes found in the Truven Health Analytics data.

Patients were included in the Truven data set if they were aged 50 to 64 years at the time of the index procedure and if they had (a) two full years of continual enrollment prior to the index procedure and (b) two full years of continual enrollment following the index procedure. The focus is on the 50- to 64-year-old age group for two reasons: More than 40% of prostate cancer cases are diagnosed before age 65, and prostate cancer is usually treated more aggressively in younger patients (SEER 2018). Aggressive treatment makes these patients more likely to experience radiotherapy-­associated toxicities.

Complications associated with radiotherapies

The Truven database analysis identified GI, GU, and SD that can arise from prostate cancer radiotherapies. The complications captured were Grade II and above (Appendix 1). Mild Grade I complications that can be controlled without medical claims are not captured in the database analysis.

For the purposes of this analysis, outpatient cost is considered to be equivalent to outpatient net payment, which is defined as the payment received by the provider excluding patient out-of-pocket and coordination of benefits (i.e., employer or plan liability). Inpatient cost is the sum of hospital net payments and physician net payments. Hospital net payment included payment received by the hospital for an admission, excluding patient out-of-pocket and coordination of benefits. Physician net payment included payment received by the principal physician (the professional who charges the most during the admission), excluding patient out-of-pocket and coordination of benefits.

Gross and adjusted costs per patient were calculated to capture and separate costs associated with patients’ pre-existing conditions prior to the index procedure. These were calculated as follows:

Gross cost per patient = total complication claims for all eligible patients divided by the number of eligible patients

Adjusted cost per patient = (total complication claims minus complication claims prior to radiotherapy) divided by the number of eligible patients

For model inputs, the adjusted cost per patient was used in order to identify and exclude claims for pre-existing complications (those claimed prior to the initial radiotherapy session). Pharmacy costs were not included.

Cost components

This cost-effectiveness analysis was developed to evaluate cost and outcome implications associated with use of a HS during prostate cancer radiation therapy from the U.S. commercial payer perspective. We focused on costs and disutility associated with radiation therapy complications. The main cost components are the HS device and its placement, and the costs associated with GI, GU, and SD complications. Radiation therapy efficacy and cost were not included.

Model assumptions

The main assumption was the HS would reduce the risk of complications equally in radiotherapies, regardless of the type or dosing intensity. Pivotal trial outcomes suggest a substantial reduction of GI toxicity related to IMRT (Mariados 2015, Uhl 2014). For the relatively novel SBRT, fewer studies, conducted with fewer patients, have evaluated outcomes with hydrogel use. However, these studies indicate that HS use with SBRT is beneficial in protecting the rectum from damage (Alongi 2013, Ruggieri 2015). A single institutional study with 200 patients treated with high dose rate brachytherapy and IMRT found considerable dosimetric rectal sparing effects with HS use (Strom 2014).

We devised two scenarios to model complication and cost reductions. In the baseline scenario, based on SpaceOAR’s pivotal trial (Mariados 2015), we assumed the HS reduces GI toxicity in prostate cancer radiotherapies, but to be conservative in our assumptions we assumed no impact on GU toxicity and SD.

In Scenario 2, based on the pivotal trial and other published results finding HS benefits in GU toxicity (Uhl 2014) and improvements in GI, GU, and sexual QoL (Mariados 2015, Hamstra 2017), we assumed the spacer reduces 70% of GI toxicity, 48.2% of GU toxicity, and 30% of SD. In both of these scenarios, we included complications identified over the two-year follow-up.

The cost of the HS and injection procedure was based on CPT codes and the Physician Fee Schedule (2018 SpaceOAR Coding and Payment Quick Reference Guide) of SpaceOAR (Boston Scientific Corporation, Marlborough, Mass.). This cost was assumed to be constant ($3,815) based on the CPT code 55874.

Appendix 3, Table 1 summarizes key features of the data and modeling assumptions.

Structure of the model

A decision-tree model (Figure 2) was developed from the U.S. commercial payer perspective, evaluating cost and patient outcomes implications associated with spacer use during prostate cancer radiotherapies. The likelihood of complications was based on the claims data analysis. The cost-effectiveness analysis was implemented using Microsoft Excel 2013. Discounting of cost and utility values was not incorporated into the analytic model due to the endpoints assessed and the short length of the modeled time horizon (two years). The primary output is the incremental cost-­effectiveness ratio (ICER) measuring cost per additional quality-adjusted life year (QALY) gained by adding HS to prostate cancer radiotherapy, compared to radiotherapy alone.

Disutility of radiotherapy complications

The model uses health-related QoL, in terms of utility scores, as an outcome measure. Utility scores represent a multi-attribute, preference-based measure of health status and provide a single index value for preferred health status, ranging from 0 (death) to 1 (perfect health) (Drummond 2005). Disutility values were assigned to each complication category, and an offset value was assigned for spacer use to reflect the assumed decreases in complications (Appendix 3, Table 2). Disutility values were derived from sources focused on prostate cancer radiotherapy (Cooperberg 2013). The model assumed complication disutilities are independent between categories. Disutility values and the spacer offset were applied to calculate the benefit to outcomes and cost per QALY saved. No discount rate was applied to disutility value because of the short timeline and a need for consistent cost assumptions.

RESULTS

Overview of Truven data set and reported costs

In the Truven claims database analysis, 74% of prostate cancer patients received IMRT, 22% received brachytherapy, and 4% received SBRT. The most frequent GI complications included colitis or gastroenteritis, hemorrhage of the anus and rectum, and diarrhea. GU complications were the most frequent for all categories of radiotherapy while SD frequency was comparable to GI complications (Appendix 4).

Appendix 5 shows gross and adjusted costs associated with GI, GU, and SD across the two-year period. Average cost per patient was highest for GI complications, associated with procedures including hyperbaric oxygen therapy, office visits, surgical pathology, metabolic scans, colonoscopy, microscopic exams, blood transfusions, and laser treatments.

Scenario 1: Baseline scenario

The two main cost components included the device and procedure costs for the spacer and costs stemming from radiotherapy complications. Under the baseline scenario, the two-year average cost per patient of each complications category was calculated. Assuming the spacer reduces 100% of GI toxicities associated with medical claims, the use of spacers is associated with an increased per-patient cost of $3,311 to achieve an additional 0.1317 QALYs over two years. The overall ICER was $21,989 per QALY. Based on a standard cutoff value of $50,000 to establish cost effectiveness, HS represent a cost-­effective treatment addition to prostate cancer radiotherapies (Table 1).

Scenario 2: Reductions in GI, GU, and SD complications

Assuming a reduction of 70% of GI toxicity, 48.2% of GU toxicity, and 30% of SD, use of the spacer is associated with an increased per patient cost of $2,759 to achieve an additional 0.2148 QALYs over two years. The overall ICER was $12,841, well under the standard cutoff of $50,000. Therefore, HS are a cost-effective treatment addition to prostate cancer radiotherapies under this scenario (Table 2).

Probabilistic sensitivity analysis of complication disutility values and spacer benefit

A probabilistic sensitivity analysis was performed by allowing all model parameters to vary. The analysis simulated 1,000 scenarios by randomizing cost and frequency input parameters within a range of ± 20% of the observed values. Spacer benefits for reduction in radiotherapy complications varied based on the Scenario 2 analysis assumptions. Range of dis­utility values for GI, GU, and SD complications varied based on disutilities cited earlier (Cooperberg 2013). Table 3 shows resulting parameter ranges.

Simultaneously varying all parameters 1,000 times over each parameter’s distribution, the sensitivity analysis resulted in ICERs between $10,200 and $63,886 per QALY gained by using spacers in patients under­going prostate cancer radiotherapies. The HS was cost effective in 98.2% of cases, using an ICER threshold of $50,000 per QALY gained, as compared to prostate cancer radiotherapy without SpaceOAR (Figure 3).

When the assumed ICER cost-­effectiveness threshold was decreased, the probability of spacers demonstrating cost effectiveness did not drop below 50% until the ICER threshold dropped to approximately $22,700.

The two-year scenario that assumed reductions in GU complications and SD in addition to GI complications, based on analyses of patient-reported outcomes from a phase 3 trial, resulted in an ICER of $12,841 per QALY. This indicates that the HS is highly cost effective. This scenario is more realistic than the baseline scenario in taking into account benefits for non-GI complications (Mariados 2015, Uhl 2014, Hutchinson 2016). Furthermore, a sensitivity analysis demonstrated that the spacer remains cost effective in the two-year time frame across a broad range of both assumed complication incidences and assumed HS effectiveness in disutility reduction. This increases confidence in the robustness of our findings. The baseline scenario, assuming no reduction in SD or GU complications but elimination of GI complications, resulted in an ICER of $23,763 per QALY gained, which would also be considered highly cost effective.

DISCUSSION

This study differed from other examinations of cost and cost effectiveness in patients with prostate cancer who have been treated with radiotherapy, in that it took into consideration a combination of clinical trial findings, expert opinions, and real-world data. Qualitative expert interviews enabled us to detail the diagnostic and treatment pathways of over 20 detrimental outcomes of radiation treatment. Informed by clinical trials and expert opinions, the database analysis was constructed to thoroughly capture cases and costs associated with all types of radiation-induced toxicities across the continuum of care. These methodological strengths allowed us to more accurately capture the full real-world cost savings and anticipated reduction of radiation-related toxicities. The methods we use also demonstrate the robustness of our findings.

Supportive data for the cost effectiveness of HS exists elsewhere in literature, although methodologies used differ from ours. Mixed results came from a decision-tree model by Hutchinson (2016) that compared 10-year costs associated with rectal toxicities across three different radiation therapy modalities. Rectal toxicity reduction rates were estimated from the phase 3 pivotal trial for SpaceOAR (Mariados 2015). The authors concluded that rectal spacers are immediately cost effective when used in high-dose SBRT, although no other modalities.

The recent cost-effectiveness study by Levy (2019) further supports the cost effectiveness of HS. This study based a Markov model on inputs estimated or calculated from the phase 3 pivotal trial for the SpaceOAR hydrogel insert, as well as published literature on the probabilities, utility, and costs of complications. The authors concluded the setting for HS insertion has a large effect, but that it is cost effective (>$100,000/QALY) in an outpatient setting, and highly cost effective (>$50,000/QALY) in an ambulatory facility. Given the difference between our methodology and that of Levy’s, the finding of cost effectiveness in both studies increases confidence in the robustness of the conclusions.

Limitations

Clinical trials and expert interviews both suggested improvements in QoL when using HS with prostate cancer radiotherapies. However, frequency and cost inputs in this study were based on the database analysis and, therefore, may not adequately capture QoL improvements not associated with medical claims. Such improvements are not directly relevant to a payer perspective, so they are not directly relevant to our purpose and analysis.

Moreover, any study utilizing administrative claims databases—the reliance on data intended for reimbursement—rather than research, comes with intrinsic limitations. Not all adverse events may be captured, so costs and incidence of these events may be underestimated. Additionally, our study was limited to a two-year time period. It is possible that differences in health-utility states could persist for longer, particularly for more serious adverse events, so our results may underestimate the benefits of HS.

Finally, we note that the incidence of complications in our data was higher than that typically seen in other studies (Mariados 2015). However, our results are based on real-world claims data, and they were robust to sensitivity analyses that varied the rate of complications. GI toxicities in multicenter trials varied from 14% to 24.9% (Lee 2016, Dearnaley 2016, Aluwini 2016, Wortel 2016), so those found in our data appear reasonable.

CONCLUSION

This study demonstrates that a HS (SpaceOAR) is a cost-effective treatment in men aged 50 to 64 years who undergo prostate cancer radiotherapy, assuming an ICER threshold of $50,000 per QALY. Payers are confronted with additional initial cost for the device and the insertion procedure, but the substantial reductions in frequency of GI, GU, and SD complications, along with accompanying improvements in QoL, outweigh that expense over a two-year time frame.

References

1. 2018 SpaceOAR Coding and Payment Quick Reference Guide. 2018.
2. Alongi F, Cozzi L, Arcangeli S, et al. Linac based SBRT for prostate cancer in 5 fractions with VMAT and flattening filter free beams: preliminary report of a phase II study. Radiat Oncol. 2013;8(171).
3. Aluwini S, Pos F, Schimmel E, et al. Hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer (HYPRO): late toxicity results from a randomised, non-inferiority, phase 3 trial. Lancet Oncol. 2016;17(4):464–474.
4. Cooperberg M, Ramakrishna N, Duff S, et al. Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis. BJU Int. 2013;111(3):437–450.
5. Dearnaley D, Syndikus I, Mossop H, et al. 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;17(8):1047–1060.
6. Drummond M, Sculpher M, Claxton K, Stoddart GL, Torrance GW. Methods for the Economic Evaluation of Health Care Programs. 3rd ed. New York, NY: Oxford University Press; 2005.
7. 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. 2017;97(5):976–985.
8. 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.
9. Hutchinson R, Sundaram V, Folkert M, Lotan Y. Decision analysis model evaluating the cost of a temporary hydrogel rectal spacer before prostate radiation therapy to reduce the incidence of rectal complications. Urol Oncol Semin Orig Investig. 2016;34(7):291.e19–e26.
10. Karsh LI, Gross ET, Pieczonka CM, et al. Absorbable hydrogel spacer use in prostate radiotherapy: a comprehensive review of phase 3 clinical trial published data. Urology. 2018;115:39–44.
11. Kishan AU, Cook RR, Ciezki JP, et al. Radical prostatectomy, external beam radiotherapy, or external beam radiotherapy with brachytherapy boost and disease progression and mortality in patients with Gleason score 9–10 prostate cancer. JAMA. 2018;319(9):896–905.
12. Lee WR, Dignam JJ, Amin MB, et al. Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. J Clin Oncol. 2016;34(20): 2325–2332.
13. Lennernas B, Majumder K, Damber J-E, et al. Radical prostatectomy versus high-dose irradiation in localized/locally advanced prostate cancer: a Swedish multicenter randomized trial with patient-reported outcomes. Acta Oncol. 2015;54(6):875–881.
14. Levy J, Khairnar R, Louie A, et al. Evaluating the cost-effectiveness of hydrogel rectal spacer in prostate cancer radiotherapy. Pract Radiat Oncol. 2019;9(2):e172–e179.
15. Mahal BA, O’Leary MP, Nguyen PL. Hydrogel spacing for radiotherapy of prostate cancer: a review of the literature. Urol Pract. 2014;1(2):79–85.
16. 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. 2015;92(5):971–977.
17. Pan HY, Jiang J, Hoffman KE, et al. Comparative toxicities and cost of intensity-modulated radiotherapy, proton radiation, and stereotactic body radiotherapy among younger men with prostate cancer. J Clin Oncol. 2018;36(18):1823–1830.
18. Prostate Cancer Foundation. Prostate cancer FAQs. www.pcf.org/faq_category/prostate-­cancer-faqs. Accessed Dec. 19, 2019.
19. Prostate Testing for Cancer and Treatment Group. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375(15):1415–1424.
20. 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.
21. SEER Cancer Stat Facts: Prostate cancer. April 2018. https://seer.cancer.gov/statfacts/html/prost.html. Accessed Dec. 19, 2019.
22. Siegel R, Miller K, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.
23. 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.
24. Susil R, McNutt T, DeWeese T, Song D. Effects of prostate-rectum separation on rectal dose from external beam radiotherapy. Int J Radiat Oncol. 2010;76:1251–1258.
25. 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.
26. Vanneste BGL, Pijls-Johannesma M, Voorde LVD, et al. Spacers in radiotherapy treatment of prostate cancer: is reduction of toxicity cost-effective? Radiother Oncol. 2015;114(2):276–281.
27. Wolf F, Gaisberger C, Ziegler I, et al. Comparison of two different rectal spacers in prostate cancer external beam radiotherapy in terms of rectal sparing and volume consistency. Radiother Oncol. 2015;116(2):221–225.
28. Wortel RC, Incrocci L, Pos FJ, et al. Late side effects after image guided intensity modulated radiation therapy compared to 3D-conformal radiation therapy for prostate cancer: results from 2 prospective cohorts. Int J Radiat Oncol Biol Phys. 2016;95(2):680–689.
29. Zietman AL, Bae K, Slater JD, et al. Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from Proton Radiation Oncology Group/American College of Radiology 95-09. J Clin Oncol. 2010;28(7):1106–1111.

Correspondence: 
Elizabeth Brooks
1231 Tech Court Suite 201
Westminster, MD 21157
Tel: (800) 580-2990
ebrooks@tti-research.com

Disclosure: The research reported in this manuscript was supported by Augmenix, a manufacturer of a hydrogel insert. However, the manufacturer had no involvement in the design of the study, the interpretation of the results, or the preparation or review of the manuscript.