Transperineal Placement of Biodegradable Material for Prostate Cancer

Number: 0926

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses transperineal placement of biodegradable material for prostate cancer.

Medical Necessity

Aetna considers transperineal periprostatic placement of biodegradable material (Barrigel, SpaceOAR) medically necessary for reducing rectal toxicity in men undergoing radiotherapy for prostate cancer.

Aetna considers transperineal periprostatic placement of biodegradebale material experimental and investigational for all other indications.

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
CPT codes covered for indications listed in the CPB:
55874	Transperineal placement of biodegradable material, peri-prostatic, single or multiple injection(s), including image guidance, when performed [SpaceOAR, Barrigel]
Other CPT codes related to the CPB:
77401 - 77417	Radiation treatment delivery [includes beta irradiation]
77767 - 77772	Remote afterloading high dose rate radionuclide skin surface brachytherapy, includes basic dosimetry, when performed
77778	Interstitial radiation source application, complex, includes supervision, handling, loading of radiation source, when performed
HCPCS codes covered for indications listed in the CPB:
SpaceOAR - no specific code:
ICD-10 codes covered if selection criteria are met:
C61	Malignant neoplasm of prostate

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Background

SpaceOAR

SpaceOAR is a biodegradable polyethylene glycol 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.  The goal of this implantation is to separate the rectum from the prostate to decrease rectal exposure during radiation treatment for prostate cancer.  SpaceOAR is completely resorbed by the body over time.

Mok et al (2014) stated that dose-escalated radiation therapy for localized prostate cancer improves disease control but is also associated with worse rectal toxicity.  A spacer placed between the prostate and rectum can be used to displace the anterior rectal wall outside of the high-dose radiation regions and potentially minimize radiation-induced rectal toxicity.

Zilli et al (2014) noted that in the curative radiotherapy of localized prostate cancer, improvements in biochemical control observed with dose escalation have been counterbalanced by an increase in radiation-induced toxicity.  The injection of biodegradable spacers between prostate and rectum represents a new frontier in the optimization of radiotherapy treatments for patients with localized disease.  Transperineal injection of different types of spacers under transrectal ultrasound guidance allows creating a 7- to 20-mm additional space between the prostate and the anterior rectal wall lasting 3 to 12 months.  Dosimetrically, a relative reduction in the rectal volume receiving at least 70 Gy (V70) in the order of 43 % to 84 % was observed with all types of spacers, regardless of the radiotherapy technique used.  Preliminary clinical results showed for all spacers a good tolerance and a possible reduction in the acute side effects rate.

The primary evidence for the SpaceOAR is a randomized controlled trial (n = 222) that found a significant reduction in late (3 to 15 months) rectal toxicity severity in the SpaceOAR spacer group (P = 0.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively (Mariados, et al., 2015). The study found similar rates of acute toxicity between groups with or without the SpaceOAR.

Other evidence for the SpaceOAR include studies of feasibility (van Gysen et al, 2014), implant stability (Pinkawa et al, 2013), prostate motion during treatment (Juneja et al, 2015), dosimetric planning studies (Pinkawa et al, 2011; van Gysen et al, 2013; Song et al, 2013; Ruggieri et al, 2015), case reports (Pinkawa et al, 2015; Teh et al, 2014), a decision analysis model (Hutchinson et al, 2016), and phase I/II studies (Whalley et al, 2016; Uhl et al, 2014),  

An Interventional Procedures Technology Assessment by the National Institute for Health and Clinical Excellence (NICE, 2017) found "[c]urrent evidence on the safety and efficacy of insertion of a biodegradable spacer to reduce rectal toxicity during radiotherapy for prostate cancer is adequate to support the use of this procedure provided that standard arrangements are in place for clinical governance, consent and audit."

van Gysen and colleagues (2014) examined the feasibility of injecting a temporary spacer between the rectum and the prostate and quantified the degree of rectal dosimetric improvement that might result.  A total of 10 patients underwent CT and MRI before and after injection of 10 cc of hydrogel and at completion of radiotherapy.  Hydrogel was injected under general anesthetic using a transperineal approach.  The primary end-points were peri-operative toxicity and rectal dosimetry (V80, V75, V70, V65, V40 and V30).  Secondary end-points were acute gastro-intestinal (GI) toxicity during and 3 months following radiotherapy and the stability of the hydrogel.  Treatment for all patients was planned incorporating volumetric modulated arc therapy with a D95 of 80 Gy in 40 fractions to the prostate and proximal seminal vesicles on both the pre- and post-hydrogel scans.  Toxicity was scored with the Common Terminology Criteria, v. 3.0.  In the first 24 hour, 2 patients described an increase in bowel movement frequency.  The comparison plans had identical prescription doses.  Rectal doses were significantly lower for all hydrogel patients for all dose endpoints (V80 = 7 % versus 0.1 %, V75 = 10.3 % versus 1.1 %, V70 = 13.2 % versus 2.7 %, V65 = 15.8 % versus 4.6 %, V40 = 35.2 % versus 23.3 %, V30 = 52.6 % versus 38.5 %; p < 0.001).  Post-treatment MRI showed gel stability.  Grade 1 bowel toxicity was reported in 6 patients during radiotherapy and 2 patients at 3 months' follow-up.  No Grade 2 or Grade 3 acute bowel toxicity was reported.  The authors concluded that SpaceOAR hydrogel was successfully injected in 10 patients with minimal side effects.  Rectal dosimetry was significantly improved in all patients.  This study has been extended to 30 patients with longer follow-up planned.  (This was a small (n = 10) feasibility study).

Pinkawa and colleagues (2015) stated that in contrast to primary radiotherapy, no reports are available for a hydrogel spacer application in post-operative salvage radiotherapy for prostate cancer.  These researchers presented the case of a 77-year old patient who presented 20 years after radical prostatectomy with a digitally palpable local recurrence at the urethrovesical anastomosis (PSA 5.5 ng/ml).  The hydrogel spacer (10 ml, SpaceOAR) was injected between the local recurrence and rectal wall under transrectal ultrasound guidance.  Treatment planning was performed with an IMRT up to a total dose of 76 Gy in 2-Gy fractions.  The same planning was performed based on computed tomography before spacer injection for comparison.  The local recurrence, initially directly on the rectal wall, could be displaced more than  1 cm from the rectal wall after hydrogel injection.  With a mean total dose of 76 Gy to the planning target volume, rectal wall volumes included in the 70 Gy, 60 Gy, 50 Gy isodoses were 0 cm(3), 0 cm(3), and 0.4 cm(3) with a spacer and 2.9 cm(3), 4.5 cm(3), and 6.2 cm(3) without a spacer, respectively.  The patient reported rectal urgency during radiotherapy, completely resolving after the end of treatment.  The PSA level was 5.4 ng/ml a week before the end of radiotherapy and dropped to 0.9 ng/ml 5 months after radiotherapy.  The authors concluded that the hydrogel spacer was successfully applied for dose-escalated radiotherapy in a patient with macroscopic local prostate cancer recurrence at the urethrovesical anastomosis to decrease the dose at the rectal wall.  This option can be considered in specifically selected patients.

Klotz et al (2013) stated that radiotherapy is an appropriate primary therapy for localized prostate cancer in accordance with urological guidelines.  Especially in tumors of higher grade malignancy, dose escalation up to 80,0 Gy seems to be an advantage; however rectum toxicity can be a problem.  By injecting a synthetic hydrogel (SpaceOAR) as a spacer between the prostate and rectum, rectal toxicity can be reduced.  These investigators reported on their experiences with 47 patients and an average follow-up of 241 days.  From February 2012 to November 2012, 47 patients were included in the study series.  Before external radiotherapy the hydrogel was injected between prostate and rectum in the so-called Denovier space.  This inter-disciplinary procedure was carried out with the patient under general anesthesia using transrectal ultrasound guidance and video documentation.  The patients were hospitalized for 1 day.  The exact position of the gel was assessed by means of magnetic resonance imaging (MRI).  Radiotherapy was initiated 7 to 14 days after gel application in a dose escalation manner by means of intensity modulated radiation therapy (IMRT) up to a dose of 80,0 Gy.  Average follow-up was 241 (100 to 386, SD 91) days.  No early side effects specific for the application were observed.  The achieved distance between rectum and the mid-plane of the prostate gland was on average 13.8 (6 to 24, SD = 3.8) mm.  Calculated V70 (rectal volume irradiated with 70.0 Gy or more) could be reduced to an average of 1.5 (0 to 8, SD = 1.7) %.  One patient showed an asymptomatic lesion of the rectal mucosa after irradiation with 38,0 Gy.  This lesion was closely controlled and gel penetration was found.  As a result radiotherapy was discontinued.  Without further treatment the necrosis had completely healed 3 months later.  The authors concluded that hydrogel application between prostate and rectum allowed dose escalation up to 80,0 Gy and appeared to reduce morbidity in patients with localized prostate cancer receiving radiotherapy.  However, they stated that before final judgment of the new technique further studies must follow.

Mariados et al (2015) reported on a prospective multicenter randomized controlled pivotal trial to assess outcomes following absorbable spacer (SpaceOAR system) implantation. Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. Spacer application was rated as "easy" or "very easy" 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. The investigators concluded that spacer application was well tolerated. Increased perirectal space reduced rectal irradiation, reduced rectal toxicity severity, and decreased rates of patients experiencing declines in bowel quality of life. The investigators stated that the spacer appears to be an effective tool, potentially enabling advanced prostate RT protocols.

Whalley et al (2014) reported on a phase I/II study of an absorbable spacer (SpaceOAR) in 30 patients with prostate cancer. All patients underwent magnetic resonance imaging before and after placement of 10 cm(3) of hydrogel. The first 10 patients had an additional magnetic resonance imaging after the completion of radiation treatment. SpaceOAR hydrogel was injected under general anaesthetic using a transperineal approach with transrectal ultrasound guidance. Primary end points were perioperative toxicity and comparison of rectal dosimetry. Secondary end points included acute and late radiation toxicity. All patients were planned on both pre- and post-hydrogel scans to a D95 of 80 Gy in 40 fractions. A contemporary control group of 110 prostate cancer patients treated with the same prescription was identified for comparison. The investigators reported that there were no perioperative complications. Rectal doses were significantly lower for the post-hydrogel plans, especially above 65 Gy (V82 = 0.2% versus 1.3%; V80 = 0.8% versus 5.3%; V75 = 2.2% versus 9.5%; V70 = 3.7% versus 12.3%; V65 = 5.4% versus 14.7%; V40 = 22.9% versus 32% and V30 = 42.7% versus 49.4%). There was no significant difference in acute grade 1 and 2 gastrointestinal toxicity, which was 43% versus 51% and 0% versus 4.5% in the hydrogel and control groups, respectively. Late grade 1 was significantly less frequent in the hydrogel group (16.6% versus 41.8%, P = 0.04). The investigators concluded that SpaceOAR hydrogel was inserted with minimal side-effects. Dosimetric benefits were greatest at higher rectal doses (V65 to V82). Late grade 1 gastrointestinal toxicity was significantly lower than that seen in patients treated without hydrogel.

Farjam and colleagues (2021) examined the impact of rectal spacing on inter-fractional rectal and bladder dose and the need for adaptive planning in prostate cancer patients undergoing stereotactic body radiotherapy (SBRT) with a 0.35 T MRI-Linac.  These researchers compared SBRT plans from prostate cancer patients with and without rectal spacer who underwent treatment on a 0.35 T MRI-Linac.  Each group consisted of 10 randomly selected patients who received prostate SBRT to a total dose of 36.25 Gy in 5 fractions.  Dosimetric differences in planned and delivered rectal and bladder dose and the number of fractions violating OAR constraints were quantified.  They also examined if adaptive planning was needed to meet constraints for each fraction.  On average, rectal spacing reduced the maximum dose delivered to the rectum by more than 8 Gy (p < 0.001).  These investigators also found that D3cc received by the rectum could be 12 Gy higher in patients who did not have rectal spacer (p < 9E-7).  Furthermore, the results showed that a rectal spacer can reduce the maximum dose and D15cc to the bladder wall by more than 1 (p < 0.004) and 8 (p < 0.009) Gy, respectively.  This study also showed that using a rectal spacer could reduce the necessity for adaptive planning.  The incidence of dose constraint violation was observed in almost 91 % of the fractions in patients without the rectal spacer and 52 % in patients with implanted spacer.  The authors concluded that inter-fractional changes in rectal and bladder dose were quantified in patients who underwent SBRT with/without rectal SpaceOAR hydrogel; rectal spacer did not eliminate the need for adaptive planning but reduced its necessity.

In a retrospective study, Zhang et al (2022) examined rectal dose reduction in prostate cancer patients who underwent a combination of volumetric modulated arc therapy (VMAT) and LDR brachytherapy with insertion of SpaceOAR.  A total of 35 patients receiving the SpaceOAR and 30 patients receiving no spacer were enrolled.  Patient was treated to doses of 45 Gy to the primary tumor site and nodal regions over 25 fractions using VMAT and 100 Gy to the prostate using prostate seed implant (PSI).  In VMAT plans of patients with no spacer, mean doses of rectal wall were 43.6, 42.4, 40.1, and 28.8 Gy to the volume of 0.5, 1, 2, and 5 cm3 , respectively.  In patients with SpaceOAR, average rectal wall doses decreased to 39.0, 36.9, 33.5, and 23.9 Gy to the volume of 0.5, 1, 2, and 5 cm3 , respectively (p < 0.01).  In PSI plans, rectal wall doses were on average 78.5, 60.9, 41.8, and 14.8 Gy to the volume of 0.5, 1, 2, and 5 cm3 , respectively, in patients without spacer.  In contrast, the doses decreased to 34.5, 28.4, 20.6 (p < 0.01), and 8.5 Gy (p < 0.05) to rectal wall volume of 0.5, 1, 2, and 5 cm3 , respectively, in patient with SpaceOAR.  To demonstrate rectal sum dose sparing, dose-biological effective dose (BED) calculation was accomplished in those patients who showed 60 % or higher overlap of rectal volumetric doses between VMAT and PSI.  In patients with SpaceOAR, average BEDsum was decreased up to 34 %, which was 90.1, 78.9, 65.9, and 40.8 Gy to rectal volume of 0.5, 1, 2, and 5 cm3 , respectively, in comparison to 137.4, 116.7, 93.0, and 50.2 Gy to the volume of 0.5, 1, 2, and 5 cm3 , respectively, in those with no spacer.  The authors concluded that the findings of this study suggested a significant reduction of rectal doses in those patients who underwent a combination of VMAT and LDR with placement of the SpaceOAR.

Barrigel

Barrigel, an injectable gel, is an FDA-cleared hydrogel spacer that is used for separation of the prostate and rectum during radiotherapy.  It is indicated to temporarily position the anterior wall of the rectum away from the prostate during radiotherapy for localized prostate cancer; and in creating this space, it is the intent of Barrigel to reduce the radiation dose delivered to the anterior rectum.  Barrigel is composed of biodegradable hyaluronic acid and maintains space for the entire course of prostate radiotherapy treatment; and it is absorbed by the patient's body over time.

In a phase-II clinical trial, Boissier et al (2017) described a technique combining the implantation of fiducials and a prostatic spacer (hyaluronic acid [HA]) to decrease the rectal toxicity following an image-guided external beam radiotherapy (EBRT) with hypo-fractionation for prostate cancer and examined the tolerance and the learning curve of the procedure.  A total of 30 patients with prostate cancer at low- or intermediate-risk were included in this trial.  Image-guided EBRT of 62 Gy in 20 fractions of 3.1 Gy with IMRT.  A transrectal implantation of 3 fiducials and trans-perineal injection of 10 cc of HA (NASHA gel spacer, Q-Med AB, Uppsala, Sweden) between the rectum and the prostate was carried out by 1 operator.  The thickness of HA was measured at 10 points on MRI to establish a quality score of the injection (maximum score = 10) and determined the learning curve of the procedure.  The quality score increased from patients 1 to 10, 11 to 20, to 21 to 30 with respective median scores: 7 [2 to 10], 5 [4 to 7], and 8 [3 to 10].  The average thicknesses of HA between the base, middle part, and apex of the prostate and the rectum were the following: 15.1 mm [6.4 to 29], 9.8 mm [5 to 21.2], and 9.9 mm [3.2 to 21.5].  The injection of the HA induced a median pain score of 4 [1 to 8] and no residual pain at mid-long term.  The authors concluded that creating an interface between the rectum and the prostate and the implantation of fiducials were feasible under local anesthesia with a short learning curve and could become a standard procedure before hypo-fractionated EBRT for prostate cancer.

Ozyigit et al (2020) stated that the optimal management of locally recurrent prostate cancer following curative radiotherapy is still unknown.  In a single-center study, these researchers examined the preliminary findings of re-irradiation using SBRT for locally recurrent prostate cancer following initial definitive local radiotherapy.  Between April 2016 and February 2019, a total of 11 patients with recurrent disease at the previously irradiated prostate were treated.  Local recurrence was detected by radiological with or without functional imaging modalities including prostate multi-parametric/pelvic MRI or positron-emission tomography (PET)-computerized tomography with (68Ga)-labelled prostate-specific membrane antigen performed after rising serum PSA level during follow-up.  All patients received SBRT to the recurrent nodule to a total dose of 30Gy in 5 fractions; HA spacer was injected between prostate and rectum in 7 patients to decrease the rectal dose.  Acute toxicity was examined by using Common Terminology Criteria for Adverse Events version 4.0, and late toxicity was examined by using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema.  At the diagnosis, the median age was 64 years, and the mean serum PSA concentration was 17.7 ng/ml.  The median interval time between local recurrence and initial definitive radiotherapy was 63 months.  Mean PSA concentration nadir value during follow-up was 0.4 3ng/ml.  With a median follow-up of 19 months, 3 patients developed either local or distant relapse; 1 patient had grade-3 acute rectal toxicity, and 1 patient had grade-2 late urinary toxicity.  These investigators did not observe any acute or late toxicity due to HA spacer injection.  The authors concluded that re-irradiation after local recurrence following initial definitive radiotherapy together with HA spacer use appeared to be safe and effective.

In a multi-center, phase-II clinical trial, Chapet et al (2021) examined the rate of late grade 2 or higher GI toxicities at 3 years, following hypo-fractionated radiotherapy (HFR) of prostate cancer with injection of HA between the prostate and the rectum.  Between 2010 and 2013, a total of 36 patients with low- or intermediate-risk prostate cancer were treated by HFR/IMRT-IGRT; 20 fractions of 3.1 Gy were delivered, 5 days/week for a total dose of 62 Gy.  A trans-perineal injection of 10-cc HA was carried out between the rectum and the prostate.  Late toxicities were evaluated between 3 and 36 months after the end of treatment (CTCAE v4).  Median pre-treatment PSA was 8 ng/ml.  Among the 36 included patients, 2 were not evaluated because they withdrew from the study in the first 3 months of follow-up, and 4 withdrew between 3 and 36 months, the per protocol population was therefore composed.  Late grade of 2 or higher GI toxicities occurred in 4 (12 %) patients with 3 (9 %) grade-2 rectal bleedings and 1 diarrhea; thus, the inefficacy hypothesis following Fleming 1-stage design could not be rejected.  None of the patients experienced late grade-3/4 toxicities.  Among the 30 patients completing the 36 months' visit, none still had a grade 2 or higher GI toxicity.  Late grade 2 or higher genito-urinary (GU) toxicities occurred in 14 (41 %) patients.  The most frequent toxicities were dysuria and pollakiuria; 4 patients still experienced a grade 2 or higher GU toxicity at 36 months.  The biochemical relapse rate (nadir + 2 ng/ml) was 6 % (2 patients).  Overall, HA was very well-tolerated with no pain or discomfort.  The authors concluded that despite the inefficacy of HA injection was not rejected, these researchers observed the absence of grade 3 or 4 rectal toxicity as well as a rate of grade 2 rectal bleeding below 10 % at 36 months of follow-up.  Late urinary toxicities were the most frequent, but the rate decreased largely at 3 years.  These researchers stated that even if it was not possible to reject the inefficacy compared to the literature, these findings suggested that a protector effect of the HA spacer during the HFR exists.

In a multi-center study, Lin et al (2021) reported on rectal dosimetry and toxicity outcomes in men with prostate cancer treated with iodine-125 low-dose-rate brachytherapy (LDR-BT) with or without polyethylene glycol hydrogel (HS) or HA rectal spacer (RS) insertion.  A total of 70 consecutive men treated with LDR-BT between December 2017 and July 2019 were included in this study, including 28 (40 %) men who had RS insertion according to the preference of referring urologist, compared to a group of 42 men (60 %) without RS.  Descriptive statistics were used to compare RS safety, dosimetric effects on organs at risk (rectum and urethra), as well as GI and GU toxicities (assessed using the CTCAE v.4) between the 2 groups of patients.  The median prostate-rectal separation with RS at mid prostate was 10 mm (inter-quartile range [IQR], 8 to 11.5 mm).  The median follow-up was 23.5 months.  There were no post-operative complications for RS insertion.  There was significantly reduced rectal dosimetry in RS-group versus non-RS group; the median RV100 was 0.0 cc (IQR, 0.0 to 0.0 cc) versus 0.4 cc (IQR, 0.1 to 1.1 cc) (p < 0.001), respectively.  The mean rectal D1cc and D2cc were 52.4 % versus 84.2 % (p < 0.001) and 45.7 % versus 70.0 % (p < 0.001) for RS and non-RS group, respectively.  There were no statistically significant differences in the mean urethral D20, D5, and D1.  There were significantly less grade-1 acute and late GI toxicities in RS-group when compared to non-RS group (0 % versus 24 %, p = 0.004 for acute GI toxicity; 4 % versus 33 %, p = 0.003 for late GI toxicity).  There were no reported acute or late grade-2 or above GI toxicities.  The authors concluded that insertion of RS in men treated with LDR-BT was safe and resulted in a significant reduction in rectal dosimetry; the reduction in rectal dosimetry with RS insertion translated into significantly reduced acute and late GI toxicities.

Latorzeff et al (2021) noted that dose-escalated EBRT is effective in the control of prostate cancer; however, it is associated with a greater incidence of rectal adverse events (AEs).  These investigators examined the dosimetric gain and safety profile associated with implantation of a new biodegradable rectal spacer balloon.  Patients scheduled for image-guided, IMRT for intermediate-risk prostate cancer were prospectively included in the French multi-center BioPro-RCMI-1505 study.  These researchers examined the dosimetric gain, implantation feasibility, AEs, and prostate-cancer-specific quality of life (QOL) associated with use of the balloon spacer.  After a scheduled review of the initial recruitment target of 50 patients by the study's independent data monitoring committee (IDMC), a total of 24 patients (including 22 with dosimetry data) were included by a single center between November 2016 and May 2018.  The interventional radiologist who implanted the balloons considered that 86 % of the procedures were easy; 20 of the 24 patients (83.3 %) received IMRT and 4 (16.7 %) received VMAT (78-80 Gy delivered in 39 fractions).  The dosimetric gains associated with spacer implantation were highly significant (p < 0.001) for most variables.  For the rectum, the median (range) relative gain ranged from 15.4 % (-9.2 to 47.5) for D20cc to 91.4 % (36.8 to 100.0) for V70 Gy (%); 15 patients (62 %) experienced an acute grade-1 AE, 8 (33 %) experienced a late grade-1 AE, 1 (4.2 %) experienced an acute grade-2 AE, and 3 experienced a late grade-2 AE.  No grade-3 AEs were reported; QOL was good at baseline (except for sexual activity) and did not markedly worsen during RT and up to 24 months afterwards.  The authors concluded that the use of a biodegradable rectal spacer balloon was safe and effective; and was associated with dosimetric gains in modern RT for intermediate-risk prostate cancer.

Teyateeti et al (2022) examined the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low-dose-rate (LDR) brachytherapy, with or without supplemental EBRT.  A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy or combined with EBRT, between January 2016 and December 2019.  Dosimetric variables reflecting the extent of rectal sparing and late rectal toxicity outcomes were evaluated.  This spacer cohort was retrospectively compared to a similar patient group (n = 139) in whom HSP was not used.  Hydrogel spacer placement was associated with significantly reduced rectal doses for all dosimetric variables; the median percentage rectal dose to 1 cc of rectum and rectal dose to 2 cc of rectum of the spacer cohort were all significantly lower compared to the non-spacer cohort.  The incidence rates of overall (any grade) and grade 2 or above rectal toxicity were lower in patients with HSP compared to patients who did not undergo HSP: 12 % and 1.8 % versus 31 % and 5.8 %, respectively . The 3-year cumulative incidence of overall rectal toxicity was significantly lower with HSP than without (15 % versus 33 %; P < 0.001), corresponding to an overall rectal toxicity reduction on univariable analysis (hazard ratio [HR] of 0.45, 95 % confidence interval [CI]: 0.28 to 0.73; p = 0.001).  In this patient cohort treated with prostate brachytherapy, none of the urethral dosimetric variables or the presence or absence of HSP was associated with late urinary toxicity.  The authors concluded that hydrogel rectal spacer placement was a safe procedure, associated with significantly reduced rectal dose; HSP translated to a decrease in overall late rectal toxicity in patients receiving dose-escalated brachytherapy-based procedures.

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References