Response to Comments: Prostate Rectal Spacers

Rectal Toxicity of Radiation Therapy for Prostate Cancer

References and/or bibliographies of published studies which evaluated the risk of rectal toxicity of radiation therapy for prostate cancer were provided.  Kim et al. (2011)(1) used the Surveillance Epidemiology and End Results (SEER) – Medicare linked database to review 41,737 patients with T1 – T2 prostate cancer, 28,088 of whom received radiation therapy with the remaining patients receiving conservative therapy.  GI toxicities at least six months after diagnosis requiring interventional procedures were measured. GI toxicity rates were 9.3 per 1000 person years after 3-D conformal therapy, 8.9 after IMRT, 5.3 after brachytherapy alone, and 20.1 after proton beam therapy versus 2.1 with conservative therapy.  The radiation therapy group continued to experience higher rates of GI toxicity even after five years post-treatment.

Hoffman et al. (2014)(2) reported late toxicity outcomes of men with localized prostate cancer randomized to receive either conventional fractionation delivering 75.6 Gy in 1.8 Gy fractions or a dose-escalated moderate hypofractionated regimen that delivered 72 Gy in 2.4 Gy fractions. Late (≥ 90 days after completion of therapy) GI toxicity rates were reported.  There was no statistically significant difference between the groups although the absolute frequency of late GI toxicity was higher in those treated with hypofractionation.  However, there was a significant difference in late Grade 2 or 3 GI toxicity when 40% or 50% of the rectum received ≥ R36.9 Gy.  There was also a significant difference in those who received ≥ R64.6 Gy to 20% of the rectum.  The authors and the commenter noted that hypofractionation is a promising way of achieving equivalent prostate cancer control with a shorter course of treatment but may be associated with higher rectal toxicities.

The commenter also noted the study of Michalski et al (2013)(3) which was performed to give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial initiated with 3-D conformal RT and amended after 1 year to add IMRT [a Radiation Therapy Oncology Group (RTOG) 0126 trial using 79.2 Gy]. The 3D-CRT patients received 55.8 Gy to the prostate and seminal vesicles followed by a boost to the prostate alone to a total of 79.2 Gy. The IMRT patients received 79.2 Gy to include the prostate and the proximal 1 cm of seminal vesicle tissue identified with the planning CT.  There were 763 patients randomized with 748 eligible and evaluated; 491 with 3D-CRT and 257 with IMRT. Acute gastrointestinal and genitourinary (GI/GU) Grade 2+ toxicity showed a statistically significant decrease with IMRT compared to 3D-CRT (p = .042). There were no differences in Grade 3+ GI/GU acute toxicities nor in acute Grade 2+ or Grade 3+ GU toxicity rates. At three years, late rectal toxicity was significantly lower with IMRT (15.1%) versus 3D-CRT (22.0%) (p = .039). Results showed patients receiving IMRT had lower bladder and rectal volumes receiving 65, 70, and 75 GY (p <.0001). The risk of late rectal toxicity was significantly reduced when less than 15% of the rectum exceeded 70 Gy (V70 15%) or less than 10% exceeded 75 Gy (V75<10%). Lower dose thresholds in the 40 Gy to 60 Gy range did not predict rectal toxicity.

Another commenter stated that a median absolute rectal dose reduction of 8.2% is associated with spacer use, which is over double the median absolute rectal dose reduction of 3.5% due to IMRT use, relative to 3D-CRT, referencing the Michalski et al (2013)(3) study above and Pieczonka et al (2016)(11).

The commenter stated that in a study of nearly 300 consecutive patients receiving IMRT, Pederson et al (2012)(4), found the risk of GI toxicity was directly related to the percentage of rectal volume receiving high dose (70 and 65 Gy) and intermediate doses (40 Gy). The results with a median follow-up of 41 months showed 4-year freedom from maximal Grade 2+ GI toxicity was 91% and by last follow-up the Grade 2+ GI toxicity was 5%. Four subsets of patients were studied using rectal DVH groupings with separate analysis for men <70 years and ≥70 years. Men in each age group and those on anticoagulation had 100% freedom from Grade 2+ (FFG2+) rectal toxicities when the rectal DVHs were V70 ≤10%, V65 ≤20%, and V40 ≤40%. The FFG2+ results were 92% for men with rectal V70 ≤ 20%, V65 ≤ 40%, and V40 ≤ 80%; and 85% for men exceeding these doses (p = 0.13). These criteria were more highly associated with GI toxicity in men aged ≥ 70 years (p = 0.06). No bladder dose-volume relationships were associated with the risk of genitourinary (GU) toxicity.

As noted in the draft LCD, we recognize that the proximity of the rectum to the prostate is a limiting factor in the safe delivery of prostate radiation. In the one randomized controlled trial of the hydrogel prostate spacer, Mariados et al (2015)(5) and Hamstra et al (2017)(6), reported pre- to post-spacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, p<.0001) whereas the control results were 12.4% and 11.7%. The planning treatment volumes were not reported and alternate methods to decrease the rectal dose were not described.  

Hydrogel Biodegradable Spacers Increase the Distance Between the Prostate and Rectum and Significantly Decrease the amount of Rectum Receiving High or Intermediate Doses

The data from Hamstra et al. (2017)(6) was submitted which showed the V50 – V80 radiation. 

• % rectal volume V50, Control 21, Spacer 10
• % rectal volume V55, Control 18, Spacer 8
• % rectal volume V60, Control 15, Spacer 5
• % rectal volume V65, Control 13, Spacer 4
• % rectal volume V70, Control 10, Spacer 2
• % rectal volume V75, Control 8,   Spacer 1
• % rectal volume V80, Control 4,   Spacer 0

We agree that there was a statistically significant decrease in the volume of rectum treated using the spacer. Percentages for volumes less that V50 were not reported which makes the comparisons to results to the DVH groupings described by Pederson et al.(4) immediately above incomplete.

Use of the Spacer to Allow Increased Prostate Radiation Dose

A history of increasing radiation doses to achieve a decrease in biochemical cancer recurrence was provided. The commenter stated the current standard of care has reached the limit of the dose that can be delivered. The ASCENDE-RT study by Morris et al (2017)(7) randomized men with intermediate- and high-risk prostate cancer after 12 months of androgen deprivation therapy.  Pelvic irradiation of 46 Gy, followed by dose-escalated external beam radiation therapy (DE-EBRT) to 78 Gy or an experimental arm that substituted a low-dose prostate brachytherapy (LDR-PB) boost occurred. The LDR-PB group was twice as likely to be free of biochemical failure at a median follow-up of 6.5 years. There was no difference in the overall survival rate between the two groups. Rodda et al. (2017)(8) reported the treatment-related morbidity. The incidence of acute and late genitourinary (GU) morbidity was higher in the group receiving the LDR-PB boost and there was a nonsignificant trend for worse gastrointestinal morbidity. (The five-year Grade 3 GI toxicity was 8.1% in the LDR-PB boost arm compared with 3.2% in the DE-EBRT group.) No difference was found in the frequency of erectile dysfunction.

We appreciate the information provided from previous studies. The unstated suggestion is that use of the spacer would allow higher doses of radiation to be provided which well may be true but is a matter of research yet to be reported.

There is Level I Evidence That Hydrogel Spacers Decrease Toxicity and Improve Health-Related Quality of Life Outcomes

Commenters included letters from individual physicians, as well as one with 48 physician signatures (with 30 indicating an academic appointment or practice at a teaching hospital), and another from a large urology group practice currently representing 148 independent urology group practices with 2,200 physicians said to be providing approximately 35% of the nation’s urology services. Letters of support for coverage were also received from the American Society for Radiation Oncology (ASTRO) and the American College of Radiology (ACR) as well as the American Urological Association (AUA). A radiation oncologist presented supporting information at the JK Open LCD meeting.

Mariados et al. (2015)(5) and Hamstra et al. (2017)(6) were consistently referenced as support with some including Hamstra et al. (2018)(9). The commenters noted that the three year incidence of Grade ≥ 2 GI toxicity was 5.7% in the placebo arm, but 0% in the hydrogel patients (p = 0.012) and that the bowel quality of life scores consistently favored the spacer group beginning at about six months after treatment with significantly more patients in the placebo group having large declines in the bowel quality of life scores.  He also noted the second paper reported that men who received the spacer had better sexual function and overall EPIC summary scores which appeared to be related to their lower penile bulb radiation dose compared to the control group.  Several commenters also referenced these findings and listed the same references.  Pinkawa et al. (2017)(10) was also cited for support. 

Hamstra et al. (2017)(6) reported on the population enrolled in the studies reported by Mariados et al. (2015)(5) and Pieczonka et al. (2016)(11) studying the extended three-year follow-up.  The patients were blinded in the Mariados study but the physicians were not. In the Hamstra 2017 study, patient participation was voluntary but not randomized although the report stated there were no differences in participation between the groups.  One hundred forty (63%) of the initial 222 subjects consented (94/149 spacer and 46/73 controls).  Median follow-up was 37 months (range 26-46) for the controls and 37.1 (range 32-47) for the spacer patients.  No Grade ≥ 2 rectal toxicity was seen in the spacer patients with four (5.6%) in the control group having Grade 2, and one Grade 3. (Results at 15 months) It was noted that the toxicity in the control group was less than usually reported and no explanation was available. The Expanded Prostate Cancer Index Bowel Composite (EPIC) quality of life (QOL) and minimally important difference (MID) tools were used to assess patient opinions of treatment. Bowel QOL declined in both groups in the first three months with return to baseline at six months.  At three years the spacer group was near or greater than baseline, but the control group had decreased (p=.002). From six months through three years, more men in the control arm had a MID in bowel QOL meeting the threshold of five points (p= 009) but no differences were found for a ten point decline. A correlation between an increasing rectal V50 to V80 and a decline in bowel QOL was found.  Urinary QOL also declined in both groups in the first three months with return to baseline at six months.  At three years, there was a statistical difference between the two groups favoring the spacer group, but the difference was only 3.9 points so it did not meet the MID level.  Disclosures for the Mariados study(5) included Augmenix, Inc. providing research funding, the lead and another author being Augmenix, Inc. shareholders, and another receiving speaking honoraria from the same source. Disclosures for the Hamstra study(6) included two authors having made investments in Augmenix, Inc. another receiving speaker honoraria, one providing consulting services; research support was provided by Augmenix, Inc.

4A. We found no clinical guidelines published by the ASTRO, ACR or the AUA addressing rectal spacers.

4B. We agree that in these studies, the spacer group had fewer instances of ≥ Grade 2 rectal toxicity.  Given the study design and number of subjects, it would be reasonable to have additional studies. For instance, there is only one RCT and there are no studies comparing use of the spacer to planning constraints designed to limit rectal toxicity.

Hamstra et al. (2018)(9) performed a secondary analysis of the population immediately above to determine sexual quality-of-life (QOL).  Ten (4%) of the initial 222 men did not answer all of the sexual QOL questions. There was no difference in average sexual QOL between the two groups after treatment.  However, since nearly 60% of men had moderate to severe sexual dysfunction at baseline, a subgroup of men (41%) with adequate baseline sexual QOL and “erections firm enough for intercourse” was analyzed and did not differ by arm [56 spacer (39%) and 34 (34%)], p = .22.  In this group of 49 men (33 spacer and 16 controls), the use of a spacer was associated with a greater likelihood of having erections firm enough for intercourse in the preceding 4 weeks (p = 0.490) which was seen from six months onward and reached a difference of 67% versus 38% at 36 months. There were no planning goals for the penile bulb dose but delivery data were collected. Disclosures included the lead and another author having small investments in Augmenix, Inc., another receiving speaking honorarium, and two providing consulting services to Augmenix, Inc.

4C: We agree with the authors who stated there are a number of limitations to post hoc subset analyses, the sample size was small, and the results must be viewed as hypothesis generating.

The Pinkawa et al. (2017)(10) report described a retrospective study of 114 patients with prostate cancer, 54 of whom were selected for hydrogel injection in a non-randomized fashion.  Patients were prospectively surveyed before RT, on the last day of RT, and a median time of 2 months, 17 months, and 63 months using the EPIC questionnaire made up of 50 items concerning urinary, bowel, sexual, and hormonal domains.  The multi-item scores were transformed linearly to a 0 to 100 scale with higher scores said to represent a higher quality of life.  A mean score change of > 5 was defined as clinically relevant: 5-10 “little,” 10- 20 “moderate,” and >20 “very much.”  The 17-month median results showed statistically significant differences favoring the spacer patients for “moderate/big problem” with bowel urgency, losing control of stools, and bowel habits, overall.  At 5 years the only measure with statistical significance was a “moderate/big problem” with bowel urgency. In the 17 month median survey 106/114 (93%) of patients gave responses, 47 (44%) of whom received the spacer.  At 5 years, only 65/114 (57%) patients responded; 19 (29%) without the spacer, and 37 of the 65 (57%) with the spacer.  A “Conflict of Interest” stated all authors reported grants and nonfinancial support (part of the hydrogel material) from Augmenix, Inc. during the conduct of the study. 

4D: The design and results of this study preclude its supporting coverage because it was not randomized, was retrospective, and the numbers of patients at five years was small.

Sylvester, Shaw, Karsh et al. (2017) were also cited by one commenter. The Karsh et al (2017)(12) review is an “accepted” manuscript which was available online November 23, 2017. It summarizes and reviews the clinical results of SpaceOAR® focusing on the Mariados et al. (2015)(5) and Hamstra et al. (2017)(6) reports. Sylvester and Shaw were listed as co-authors in these two papers.  Financial disclosures indicated each author was a study investigator, one was also stockholder, and two others were paid consultants to the sponsor Augmenix, Inc., the manufacturer of the SpaceOAR® system.

4E: We appreciate the additional literature. The authors’ conclusions were that the spacer application is safe and well tolerated, and that the created space significantly reduces rectal injury leading to long-term benefits. We note this was another paper for which the authors had a potential conflict of interest.

Other References Received 

Padmanabhan et al. (2017)(13) reviewed the use of hydrogel spacers in prostate radiotherapy.  Conclusions were that, “The current data show promise, but further studies with longer follow-up would be useful to pave the way for hydrogels as a cost-effective standard of care in radiation therapy for prostate cancer.”  The authors noted no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.  Serrano et al (2017)(14) included tissue spacers in their review of methods to reduce rectal injury in men receiving prostate cancer radiation therapy.  Concluding statements were, “The use of these spacers is promising as they show significant reduction in acute and late toxicities.  However, longer follow-up is needed as there is currently only one published phase III trial with a 3-year follow-up.”  No potential conflicts of interest were disclosed.

We appreciate having these references to review and agree with the conclusions.

Miscellaneous

A commenter was concerned that the draft LCD had included the phrase “comparing different spacers are needed” from the final ECRI report/statement.(15) He felt that did not change the conclusion that the biodegradable hydrogel spacer is safe, effective in reducing bowel toxicity, and improves quality of life in these patients. In addition, the commenter stated most of the late GI toxicity occurs in the first two years following treatment and in Hoffman’s study, only one event had occurred in the third year.

The ECRI Executive Summary has this “Conclusion” which favors a longer period of observation for toxicity. (15)

SpaceOAR® hydrogels are well tolerated and work as intended to reduce rectal irradiation, long-term (but not acute) rectal toxicity, and improve bowel qualify of life (QOL) based on 1 randomized controlled trial (RCT and 3 non-RCTs). A comparative study found that neither SpaceOAR® nor a competing spacer (BioProtect Prospace) reduced acute rectal toxicity (< 3 months). Studies with longer follow-up (> 5 years) that compare different spacers are needed; an ongoing study will provide 5-year data.(15)

Palmetto has removed the spacer code (0438T) from its Category III CPT Code LCD listing non-covered codes in October 2017.

We are aware of the Palmetto LCD but did not reach the same conclusion when reviewing the evidence. Currently, MACs may be paying claims for spacers but no MAC has an LCD of positive coverage.

The National Institute for Health and Care Excellence (NICE) “Biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer” guideline, published August 23, 2017 (16), was provided.  Also received was the Kaiser Permanente Clinical Review Criteria, “SpaceOAR® (Spacing Organs at Risk).”  National Comprehensive Cancer Network (NCCN) guidelines (17) were also cited suggesting they recommended use of a spacer.

The NICE document cited findings from the one RCT.  Ten safety events were listed.  Recommendations were that, “Current evidence on the safety and efficacy of insertion of a biodegradable spacer to support the use of this procedure provided that standard arrangements are in place for clinical governance, consent, and audit.” (16) Although Kaiser Permanent decided that the SpaceOAR® met their medical technology assessment criteria, the conclusion of the Medical Technology Assessment Committee (MTAC) was:

• There is insufficient published evidence to recommend for or against the use of SpaceOAR® in prostate cancer patients treated with external beam radiotherapy.

• The only published RCT trial to date, had its limitations and does not provide sufficient evidence to determine the long-term safety and efficacy of the hydrogel spacer, or to determine its effect on the net health outcome outside the investigational setting.

The NCCN Guidelines Version 2.2018 for Prostate Cancer simply state that “Perirectal spacer materials may be employed when the previously mentioned techniques 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.” (17)

The new Category I code, 55874 (Transperineal placement of biodegradable material, single or multiple injection(s), including image guidance, when performed), would not allow it to be used for “Interstitial balloons” or other non-biodegradable material as the draft LCD had suggested.

We agree and will remove that statement.

Lack of Heterogeneity in Patients Studied

A commenter noted that the one RCT does not address the variations seen in prostate cancer patients, especially those with co-morbidities. Inflammatory bowel disease, diabetes, anticoagulation or anti-platelet therapy, and pre-existing hemorrhoids would be considerations.

Men with T1 or T2 prostate cancer, a Gleason score of 7, a prostate-specific antigen (PSA) concentration of 20 ng/mL, and a Zubrod performance status 0 to 1 were included in the RCT. Exclusion criteria included a prostate volume of 80 cm³, extracapsular extension of disease or 50% positive biopsy cores, metastatic disease, indicated or recent androgen deprivation therpay, and prior prostate surgery or radiation therapy.

One can understand the desire for homogeneity in the initial study population.  However, most commenters did not make this point and seemed eager to use the spacer in any patient for whom radiation therapy for prostate cancer was planned. If spacer use is planned for a wider population than currently studied, it would seem reasonable to ask that such studies be performed prior to wide acceptance of its use. Co-morbidities were not mentioned by those favoring coverage for the spacer, but IBD was specifically raised as a concern by a commenter.

A literature search addressing patients with IBD receiving prostate cancer radiation was performed and portions are summarized here. Song et al. (2001)(18) and Bosch et al. (2017)(19) reported on patients with IBD who received radiation and chemotherapy.  Murphy et al. (2015)(20) studied 84 men, 63 of whom served as matched control and 21 with IBD: 13 with ulcerative colitis, 7 with Crohn’s disease, and 1 with not otherwise specified IBD. Patients who had had a flare in the year preceding the prostate cancer diagnosis were excluded as were those in the midst of an active flare. Twenty of the 21 men (95.2%) completed therapy and were flare free during therapy. Follow-up was for five years. There was no statistical difference in acute or late toxicity between these men and the controls. The use of IDB medication during therapy was the only significant predictor of acute > Grade 2 GI toxicity. The authors concluded the presence of IBD may not be an absolute contraindication but perhaps a relative contraindication. They also noted the small sample was inadequate to conclude radiation therapy results in acceptable toxicity risk. Gestaut et al. (2017)(21) performed a retrospective review of 18 patients out of the 166 in the tumor registry of patients with IBD and prostate carcinoma. Patients were excluded from review if they first had surgery and then salvage RT or if they were currently having an active IBD flare. Only patients in remission or on medical maintenance therapy for IBD were included. Twelve were treated with EBRT, three received 3D-CRT and six had IMRT. Average length of follow-up was 12 years. Grade 1 diarrhea decreased post-radiation but proctitis was zero Grade before and 17% for Grades 1 and 2 each post-radiation. All patients with Grade 2 proctitis received 3D-CRT. The authors concluded that patients can be given radiation therapy without concern for significantly increased late GI toxicity in the moderan era of IMRT. The small number of patients in each study makes conclusions elusive.

Searching for the outcomes of patients on anticoagulation (AC) therapy who receive RT for prostate cancer, we were directed back to one study noted above (Pedersen et al. - 2012)(4) and two others (Choe et al. - 2010(22)  and Chennupati et al – 2014 (23)). Given the findings between planning and rectal toxicity, we have summarized the results.   Choe et al.(22) studied 568 patients with prostate cancer who received 3D-CRT or IMRT. Seventy-nine were taking warfarin (55/69.6%) or clopidogrel (24/30.4%); 56 (70.9%) had been taking AC prior to RT and 23 (29.1%) started AC post-radiation.  Gastrointestinal (GI) bleeding occurred more often than genitourinary (GU) bleeding.   Thirty-one (39.2%) developed GI bleeding and 38 (48.1%) had heme positive stools. Nine patients with GU bleeding also had GI bleeding.  The median follow-up was 48 months. The four-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receiving AC versus 3.6% for those not receiving AC (p <.0001). Multi-variate analysis showed AC therapy was the only significant factor associated with Grade 3 or worse bleeding which was 38.2%. Higher radiation dose, previous transurethral resection of the prostate, and IMRT were associated with Grade 2 or worse bleeding toxicity. Analysis of rectal dose volume histograms available for 55 of the 79 AC patients showed Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving ≥70 Gy was <10% or the rectum receiving ≥50 GY was <10%. 

Pedersen et al. (2012)(4) at the same institution reported on the GI and GU toxicity of 296 consecutive men treated with IMRT between 2000 and 2007 and proposed dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity.  The median dose was 76 Gy, median follow-up was 41 months and the four-year freedom from maximal Grade 2+ toxicity was 81% for GU and 91% for rectal toxicity.  Results are listed below.

Rectal DVH and Freedom from Grade 2+ GI toxicity at 4 years for patients <70 years of age were: 

• Rectal DVH (V70 < 10%, V65 < 20%, and V40 < 40%) =100%
• Rectal DVH ( V70 < 15%, V65 < 30%, and V40 < 60%)= 93%
• Rectal DVH ( V70 < 20%, V65 < 40%, and V40 < 80%)= 90%
• Rectal DVH (None of the above)= 93%

Rectal DVH and Freedom from Grade 2+ GI toxicity at 4 years for patients ≥70 years of age were: 

• Rectal DVH (V70 < 10%, V65 < 20%, and V40 < 40%) =100%
• Rectal DVH ( V70 < 15%, V65 < 30%, and V40 < 60%)= 91%
• Rectal DVH ( V70 < 20%, V65 < 40%, and V40 < 80%)= 92%
• Rectal DVH (None of the above)= 75%

Chennupati et al (2014)(23), also at the same institution, studied 372 consecutive men between 2001 and 2010 who received IMRT with daily image guidance beginning in 2003.  Rectal planning constraints were tightened in 2007 at V70 ≤ 10%, V65 ≤ 20%, and V40 ≤ 40%.  Men had relaxed contraints of V70 <20%, V65 <60%, and V40 <80% if they had received treatment to an initial pelvic nodal field.  Median follow-up for late toxicity was 47 months from the end of RT.  For all patients, the Freedom from Grade 2 (FFG2) GI toxicity was 94% at 2 years and 92% at 4 years.  The 58 men who met the optimal rectal planning criteria (V70 ≤10%, V65 ≤ 20%, and V40 ≤ 40%) had FFG2 GI toxicity of 100% at 4 years compared to 93% for the men not meeting these criteria (p = 0.03).  Quality of life (QOL) data collection began in 2007 using EPIC domain scores.  For the patients meeting the more strict rectal constraints, 2% of patients reported bowel distress or dysfunction at 24 months post-treatment.  Overall bowel QOL scores at four years were higher than those not meeting the constraints (median value 100 vs. 96, p = 0.05). This information provides data to support methods to minimize rectal toxicity in patients on AC without the need of a spacer.

Summary

We appreciate the many comments we received, the bibliographies, and the references.  We remain concerned that there is only one randomized controlled trial of the prostate rectal spacer. Reported follow-up is currently a three-year period. There have been no other RCTs of a more diverse population of patients, those with co-morbidities known to affect radiation therapy for prostate cancer outcomes, and other RT modalities. We would hope such trials occur and also that consideration be given to increasing the rectal planning constraints with reported outcomes. Reducing rectal radiation exposure during prostate cancer radiotherapy is obviously desirable, but there is insufficient evidence to demonstrate this requires spacer implantation. Therefore, rectal spacer implantation is not considered reasonable and necessary in the Medicare population.

Bibliography

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17. NCCN Guidelines Version 2.2018 for Prostate Cancer
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