Perirectal Space Research Articles

Rectourethral fistula after perirectal spacer placement requiring pelvic exenteration

Despite the widespread use of perirectal spacers to reduce radiation-induced rectal toxicity during prostate cancer treatment, postmarketing data reveal rare but significant complications. This case report details a severe complication of rectourethral fistula necessitating robotic pelvic exenteration with urinary and faecal diversion following perirectal spacer placement. Although SpaceOAR has been shown to reduce rectal radiation dose, the ensuing clinical benefit remains inconclusive in real-world data. Our findings underscore the need for thorough patient counselling regarding the risks and benefits of spacer use, particularly given the lack of evidence for improved cancer control or gastrointestinal toxicity. We further review the literature to highlight the importance of physician technique during placement and the potential avenues for early identification and management of complications. Future research must aim to better characterise real-world risks and develop strategies for mitigating severe outcomes.

Prospective, Randomized Controlled Pivotal Trial of Biodegradable Balloon Rectal Spacer for Prostate Radiation Therapy

Purpose/ObjectivesRectal spacers have been shown to reduce rectal side effects in patients receiving prostate radiation. However, concerns remain regarding precise and reproducible gel injection. We evaluated efficacy and safety of a novel rectoprostatic spacer balloon which allows potential for controlled, adaptable deployment. This study tested co-primary hypotheses: 1) Balloon spacer would result in ≥ 25% reduction of rectal V70 in > 75% of subjects, and 2) Implantation procedure-related and rectal ≥ Grade 1 adverse events within 6 months (duration ≥ 2 days, CTCAE 4.0) would be non-inferior in balloon vs control subjects. Materials/Methods222 subjects were enrolled at 16 centers. All patients had T1-T3 prostate cancer without MRI evidence of posterior extraprostatic invasion. Randomization was 2:1 (balloon: control) and subject-blinded. Patients underwent transperineal TRUS-guided fiducial placement +/- balloon, followed by IMRT (81 Gy in 1.8 Gy fractions or biologically equivalent hypofractionated dose). For efficacy comparisons, plans were generated by a central core lab on pre- and post-implant CT scans. ResultsThe primary efficacy endpoint was met, with 97.9% of balloon subjects (139/142) having rectal V70 reduction >25% (p<0.001). Mean V70 was 7.0 % pre- vs 1.1% post- implant. The primary safety endpoint was met with balloon subjects experiencing fewer ≥ Grade 1 events, 18% vs 23% (p < 0.001 for non-inferiority). On pre-defined secondary endpoint of ≥ Grade 2 events, rates trended lower in balloon subjects (4.3% vs 6.5%, p=0.527). Mean perirectal spacing was 19 ±3.7mm and maintained through radiation treatment (18 ±3.9mm). Balloon resorption was observed on 6-month CT in 98.5% (133/135) of subjects. The EPIC QOL instrument was collected throughout study, and did not differ statistically between the study arms. ConclusionsBiodegradable rectal spacer balloon was effective in significantly reducing dose to rectum, and associated with decreased cumulative rectal plus implantation-related adverse events. Balloon resorption was consistently observed by 6 months.

Acute Toxicity and Early Prostate Specific Antigen Response After Two-Fraction Stereotactic Radiation Therapy for Localized Prostate Cancer Using Peri-Rectal Spacing–Initial Report of the SABR-Dual Trial

Purpose: SABR-Dual is a phase III trial with an initial phase-I safety cohort, of two-fraction stereotactic radiotherapy (SABR) with optional MRI-based focal boost, using peri-rectal spacing, for localized prostate cancer. This represents the initial report from the phase-I non-randomized cohort. Materials and methods: Subjects had favorable intermediate risk (FIR) or low risk (LR) prostate adenocarcinoma, and gland volume <80cc. All underwent radiopaque hydrogel spacer and fiducial marker placement prior to simulation (CT and 3-tesla T2 MRI). The clinical target volume included the entire prostate, and in FIR patients, 1-2cm of seminal vesicle (SV). A 2mm expansion was applied for planning target volume (PTV), and a dose of 27 Gy was prescribed to the PTV-prostate, 23 Gy to the PTV-SV, with an optional 30 Gy simultaneous boost (SIB) to an MRI-defined dominant lesion. Primary endpoint was 3-month patient-reported changes in quality of life based on the EPIC-26, IPSS, and SHIM questionnaires. Secondary endpoints were 6-month quality of life, acute toxicity (using CTCAEv5) and early PSA response. Results: Among the 20 patients in the phase-I cohort, 95% had FIR disease, and 50% received an SIB. At median follow-up of 8 months, a 3-month minimally clinically important change occurred in 1/20 (5%), 6/20 (30%), 2/20 (10%), 4/20 (20%), and 5/20 (25%) in urinary incontinence, urinary obstructive, bowel, sexual, and hormonal domains. There was a mean increase of 1±5.4 in IPSS and decrease of 1.8±6.5 in SHIM scores. Rates of grade 2 urinary and bowel toxicity 10% and 0%, respectively, with no grade ≥3 toxicities. Mean PSA decrease at last follow-up was 70.4%±17.7%. Conclusion: This generalizable protocol of two-fraction prostate SABR using peri-rectal spacing is a safe approach for ultra-hypofractionated dose-escalation, with minimal acute toxicity. Longer-term outcomes and direct comparison with standard 5-fraction SABR are being studied in the phase-III randomized portion of SABR-Dual.

Extravasated Pudendal Artery Pseudoaneurysm Presenting as a Large Vaginal Hematoma Following Uncomplicated Delivery

Body of Abstract: (1) To report a case of an extravasated pudendal pseudoaneurysm presenting as vaginal hematoma following an uncomplicated delivery. (2) To discuss alternatives of management of vulvar hematomas. Introduction: Postpartum hemorrhage is a leading cause of maternal mortality and can infrequently (1/300-1/1500 deliveries) be caused by vulvar hematomas. Vulvar hematomas are typically small and resolve with conservative treatment. Rarely, they can develop rapidly, posing a significant risk to the patient. Risks for vulvar hematomas include a prolonged second stage of labor, multiple gestation, operative vaginal delivery, episiotomy, and vaginal laceration. Extravasation from a pseudoaneurysm in the pelvic arteries is a rare cause of vulvar hematomas (&lt; 5% of cases) with &gt;75% involving the uterine artery. Pseudoaneurysms typically result from damage to vasculature during a traumatic delivery. Spread into the retroperitoneal space can lead to shock and eventual demise if improperly managed. This case illustrates the exceptionally rare occurrence of a pudendal artery pseudoaneurysm with rapidly expanding potentially catastrophic hematoma formation. Case Summary: Presented is a 21-year-old G2P1011 patient at 39w5d with a large vaginal hematoma diagnosed shortly following spontaneous vaginal delivery. The case initially presented to the hospital one hour after spontaneous rupture of membranes with an unremarkable pregnancy. Normal labor ensued and stage II of labor lasted one hour with an uncomplicated nonoperative vaginal delivery. Postpartum a significant increase in fundal height was noted. Cytotec was given and bladder catheterization removed 800 ml urine. Abdominal pain increased. Vital signs were normal. Exam revealed a large posterior vaginal wall swelling extending upward, but without active bleeding. A computerized tomography (CT) scan of the abdomen/pelvis revealed a 9.7 X 10.5 X 13.2 cm pelvic hematoma arising from the posterior vaginal wall with extension cephalad into the perirectal space and right adnexa. Evidence of active bleeding and bilateral hydronephrosis were reported. Hemoglobin was 10.1, down from admission 12.5. Symptoms included worsening abdominal pain and dizziness. Based on the active bleeding noted on CT scan and the progressive symptoms, the patient was transferred to a tertiary care center. Upon tertiary center admission the patient was tachycardic and hypotensive (P 153 and BP 101/61). Hemoglobin was 9.3. Physical exam was unchanged. Interventional radiology recommended and patient underwent embolization of bilateral uterine arteries for treatment of a diagnosed pseudoaneurysm with extravasation of the right pudendal artery. Postpartum day 1, mild right lower quadrant pain was felt to be consistent with the embolization. Hemoglobin decreased to 6.5, and the patient received one unit of packed red blood cells (PRBCs). Clinically, ambulation was tolerated, but tachycardia and hypotension remained and there was decreased swelling. Hemoglobin remained low at 6.8, and another unit of PRBCs was given. Hospital course thereafter was uneventful and discharge was on day 3. Discussion: This case describes a vaginal hematoma and pudendal artery pseudoaneurysm as a very rare but potentially life-threatening postpartum hemorrhage following vaginal delivery. Association with an uncomplicated pregnancy and delivery, involvement of the pudendal artery with an expanding large hematoma dissecting the retroperitoneal space creating a hemodynamically unstable situation are only rarely seen concurrently. Hematoma treatment starts conservatively, utilizing ice, rest, and pain control if patient is hemodynamically stable and the hematoma is small. When large, rapidly expanding, or the patient is hemodynamically unstable, surgical intervention or artery embolization should be considered when imaging identifies the source of bleeding. Imaging may include ultrasound, CT, CT angiography, and magnetic resonance imaging as options for localization of hematoma. No superior mode of evaluation is identified. Pseudoaneurysms following delivery have most commonly been described in the uterine arteries with only a handful of case reports documenting other sources including the obturator, labial, vaginal, and internal pudendal arteries. Our case demonstrates that extravasated pelvic artery pseudoaneurysms can present in benign appearing nonoperative deliveries and should be considered in the differential diagnosis as a source of post-partum hemorrhage. Recently, pseudo-aneurysms have more commonly been treated with IR artery embolization as it is a less invasive and better tolerated procedure by patients. Tsumagari et al suggested an algorithm proposing vulvovaginal hematomas should be observed versus surgically evacuated, whereas upper vaginal hematomas should undergo CT angiography for assessment for selective arterial embolization. Conclusion: Pseudoaneurysms of the pudendal artery with hematoma formation occurring in an uncomplicated delivery are an extremely rare cause of potentially life-threatening hemorrhage as reported in only a handful of cases. Because of their potential for catastrophic sequelae, they should be considered in the differential diagnosis of expanding upper vaginal hematomas. This case depicts the importance and success of rapid identification and embolization of pudendal artery pseudoaneurysm to prevent mortality.

Re-thinking of "pelvirectal space"

Before the "mesorectal" theory was proposed, the traditional anatomy believed that the "pelvirectal space" belonged to the anal canal and perirectal space, which was independent of the rectal structure, located on both sides of the rectum, above the levator ani, and below the peritoneal reflexion, and was composed of a large amount of fatty tissue filling. With the development of the theory of membrane anatomy and the clarification of the concept of "rectal mesentery", combined with the author's clinical experience, we found that the above-mentioned fat is actually the fat within the mesorectum, as well as the fat tissue of lateral lymph nodes (LLN) such as the internal iliac lymph nodes (No.263) and obturator lymph nodes (No.283) on both sides of the rectal mesentery, rather than the so-called fat tissue within the interstitial space. Therefore, the author believes that the pelvirectal space does not exist. In the anatomical location equivalent to the pelvic rectal space, there is the "superior levator ani space" based on the membrane anatomy theory. From the pelvirectal space to the superior levator anal space, it reflects our further understanding of the anatomy of the rectal mesentery.

Association of Apical Spacing with Bowel Quality-of-Life: A Secondary Analysis of the Hyaluronic Acid Randomized Trial.

Recently, a randomized trial (NCT04189913) reported that a hyaluronic acid (HA) rectal spacer reduced acute grade 2+ gastrointestinal (GI) toxicity for hypofractionated radiation therapy (RT). However, 26.5% of patients who received the spacer experienced a minimally clinically important difference (MCID; 5 points) in EPIC bowel quality-of-life (QOL). We evaluated whether characteristics of the spacer implant, particularly apical separation, were associated with change in bowel QOL at 3-months and acute grade 1+ GI toxicity. We conducted a secondary analysis of 136 patients randomized to receive the HA spacer. The post-spacer implant structure sets and treatment plans were analyzed. The mid-plane (MP) was defined as the prostate center-of-mass. Four horizontal planes were defined at the superior (MP +1 cm), mid-gland, inferior (MP - 1 cm), and apex of the prostate. Separations between the prostate and anterior rectal wall at midline were computed at each plane in a custom Python programming environment. Implant symmetry was computed based on a previously published method (Fischer-Valuck, PRO, 2017). The volume of rectum receiving > = 30 Gy (rV30) was extracted from DVHs; rV30 has been associated with bowel frequency, fecal incontinence, and rectal pain for hypofractionated RT (Wilkins, IJROBP, 2020). First, we evaluated whether any of the 4 separation or symmetry variables were associated with rV30. Then, we evaluated whether significant spacing variables, rV30, and baseline bowel QOL were predictive of the change in bowel QOL at 3-months using multivariate linear regression. Finally, we evaluated whether significant spacing variables and rV30 were predictive of acute grade 1+ GI toxicity (21 events) within 3-months, utilizing multivariate logistic regression. The mean (standard deviation) superior, mid-gland, inferior, and apex separations were 15.6 (SD 6.0), 12.7 (3.7), 11.2 (3.7), and 9.7 (4.0), respectively. 130 of 136 (95.6%) had a symmetry score of 1 (symmetric). Apical separation was the only variable significantly associated with rV30 (r = -0.32; p < 0.01). On multivariate analysis, apical separation (0.41/mm; p = 0.01) was significantly associated with the change in bowel QOL, after adjusting for baseline bowel score (p = 0.0002) and rectum V30 (p = 0.50). Mean (SD) changes in bowel QOL were 0.01 (5.9) and -3.7 (8.1) for apical separations > = 10 vs <10 mm, respectively. Respective percentages of patients with a bowel MCID were 14.8% and 36.6% (p = 0.006). However, apical separation was not associated with increased odds of experiencing grade 1+ GI toxicity (p = 0.98), when adjusted for rectum V30 (odds ratio 1.04; p = 0.04). Increased apical separation may be associated with improved EPIC bowel QOL at 3-months for patients who received a HA rectal spacer prior to hypofractionated RT. This finding is clinically important, because HA can be deliberately injected into the perirectal space at the level of the prostate apex.

Mapping the Anatomical Distribution of MRI-Identified Locoregional Recurrence following Robotic-Assisted Laparoscopic Prostatectomy for Prostate Adenocarcinoma

The pattern of locoregional recurrence specifically after robotic-assisted laparoscopic prostatectomy (RALP) for prostate adenocarcinoma is still unknown. In this study, we reviewed pelvic magnetic resonance images (MRI) after postoperative biochemical recurrence (BCR) and drew a map of locoregional recurrence to support evidence of determining the optimal target volume of salvage radiotherapy in a post-RALP BCR scenario. We have retrospectively searched 7,583 prostate adenocarcinoma patients who have received RALP in our institution between January 2010 and December 2021, and found a pool of highly selected patients with gross tumor recurrence confirmed by post-BCR pelvic MRIs and did not have other histories of malignancy. BCR was defined as the serum PSA more or equal to 0.2 ng/mL, or three consecutive increases. Patients with serum PSA nadir more or equal to 0.2 ng/mL on the 90th postoperative day (POD 90) were excluded to guarantee successful tumor removal. We have reviewed serum PSA levels using R codes, MRI and pathological reports using Excel, and descriptive statistics using SPSS 25. The gross lesions were contoured on the correlating MRIs using MIM Maestro 7.1. The RT structure DICOM files were merged into a map using MATLAB 2022b. In addition, we have conducted Fisher exacted test, Mann-Whitney U test, and logistic regression to identify risk factors for regional recurrence. A total of 173 patients were identified with locoregional recurrence from post-BCR pelvic MRIs, and 139 (80.3%) patients were in the high-risk group or very-high-risk group according to the NCCN guidelines: 57 (32.9%) patients with histological grade group 5, 50 (28.9%) patients with initial PSA over 20 ng/mL, 114 (65.9%) patients with extracapsular extension, 55 (31.8%) patients with seminal vesicle invasion, and 15 (9%) patients with pN1. The median follow-up was 4.7 (IQR 2.8-6.9) years for pelvic MRIs and 5.8 (IQR 4.0-8.6) years for serum PSA. The BCF survival was median of 10.7 (IQR 4.6-19.1) months, and the locoregional recurrence-free survival was median of 24.6 (IQR 9.7-49.4) months for this subgroup of patients. At first locoregional recurrence, 148 (85.5%) patients were local only, 20 (11.6%) patients were regional only, and 5 (2.9%) patients were both local and regional. Out of the 25 patients with regional recurrence, the incidence of gross tumor recurrence differed by nodal sites: 3 (12%) in perirectal space, 5 (20%) in internal iliac, 7 (28%) in obturator, 13 (52%) in external iliac, and 6 (24%) in common iliac lymph nodes. We have found 173 patients and were able to map reliable gross tumor recurrence sites after RALP and confirmed by pelvic MRIs following BCR. The map supports evidence of using the existing consensus pelvic clinical target volume of salvage radiotherapy, in a post-RALP BCR scenario.

A Hybrid Intelligence (HI) System for Segmenting Rectoprostatic Spacer Gel and Key OARs on CT Images for Prostate Cancer Radiation Therapy Planning

Our hybrid intelligence (HI) system, combining natural and artificial intelligence, is effective for auto-contouring H&N and thorax organs at risk (OARs) for radiation therapy (RT) planning with FDA 510(k) clearance. The purpose of this study is to test the HI system to segment a commercially available retroprostatic hyaluronic acid spacer gel (RSG) and pelvic OARs in planning CT images for prostate cancer RT. HI can achieve clinically acceptable auto segmentation for tissue-equivalent RSG in this domain. RSG is injected in the peri-rectal space in men with prostate cancer prior to RT to minimize rectal toxicity. 190 patients with prostate cancer were included in this post-hoc image analysis from a multi-center, prospective, randomized trial, with 136 in the spacer arm. The HI system has 3 steps: rough recognition from fuzzy model (FM) based automatic anatomy recognition (AAR-R), deep learning-based recognition (DL-R) refinement, and deep learning-based delineation (DL-D) to contour objects guided by the recognition results. FM encodes high level 3D anatomy knowledge of object shape and its relationship with other OARs; DL-R and DL-D focus on pixel-level details. The 190 studies are divided into disjoint training (100) and testing (90) subsets. 100 samples are used in DL-R and DL-D training, with 45 to build the FM for AAR-R. RSG and 4 other OARs (pelvic skin, prostate, bladder, rectum) are contoured. Location error (LE) is used to evaluate recognition; Dice coefficient (DC) and Hausdorff distance (HD) are employed to evaluate delineation. Acceptability scores (AS) (range 1-5, 1 for poor quality, 5 for best quality) from an observer study are recorded for HI-output and ground truth masks of RSG for assessing segmentation quality. The HI system achieves highest DC (0.94±0.07) and lowest HD (1.96±1.61 mm) for bladder, for rectum and prostate similar DC (0.82±0.08) and HD (2.62±1.65mm), for RSG, the most challenging object, a good DC close to 0.7 (0.67±0.10) and excellent HD (2.66±1.44mm). AS for auto-segmentations (3.86±0.85) were significantly better than those for ground truth segmentations (3.45±1.00) (p = 0.02, paired t-test). Table 1 summarizes results. The HI system achieves clinically acceptable segmentations for pelvic OARs and significantly better acceptability of segmentation of RSG compared to clinically performed ground truth segmentations. This has implications in improving efficiency and accuracy of CT-based RT planning in patients with prostate cancer.

Real-World Complications of the SpaceOAR Hydrogel Spacer: A Review of the Manufacturer and User Facility Device Experience Database

To characterize adverse events related to use of the perirectal spacing agent SpaceOAR, we examined the Manufacturer and User Facility Device Experience (MAUDE) database. The MAUDE database was queried for "SpaceOAR" and "Augmenix" from June 2015 (when SpaceOAR was approved by the Food and Drug Administration) to October 2022. Reports were reviewed for adverse events (AEs), operative procedures performed because of the AE, and changes to the radiation plan. AEs were categorized using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Six hundred fifty-four reports were reviewed. Eighty-four were excluded and 4 reports reviewed 2 separate cases of SpaceOAR administration. Five hundred seventy-four cases were ultimately included. Three deaths were reported (0.5% of all AEs). One point six percent of cases represented CTCAE grade 4 injuries (life-threatening consequences; urgent intervention indicated), 15.9% grade 3 (severe but not immediately life-threatening; hospitalization), 24.2% grade 2 (moderate; local/noninvasive intervention), and 57% of events were CTCAE grade 1 (mild; asymptomatic or mild symptoms). Bowel diversion occurred in 29 cases (9%). Both asymptomatic (n=311) and debilitating (n=12) complications of SpaceOAR hydrogel use were identified. Death, gel embolization, anaphylaxis, rectal ulcerations, and infections requiring bowel or urinary diversions were among the complications reviewed. Providers should consider these potential complications before perirectal spacer administration and during patient counseling.

Relationship between seminal vesicle displacement and distribution of hydrogel spacer within the perirectal space in prostate radiotherapy.

The influence of a hydrogel spacer (HS) on seminal vesicle (SV) displacement in prostate radiotherapy was examined in the present study. A total of 20 patients with prostate cancer, who received intensity-modulated radiation therapy (IMRT), were enrolled. Computed tomography and magnetic resonance imaging were performed before and after HS insertion within the peripheral space for IMRT planning. Before and after HS insertion, The SV was delineated, and the amount of SV displacement was evaluated. Large SV cranial displacements (≥0.50 cm) were observed in 25% of patients. A HS lateral distribution of ≥1.00 cm in the upper two slices (midgland + superior) influenced the SV cranial displacements (P<0.01) and was associated with large SV cranial displacements (≥0.5 cm) (P<0.01). The HS cranial distribution in the upper slices did not influence SV cranial displacements (P=0.16). In addition, any HS lateral distribution of ≥1.00 cm in all slices did not induce the SV lateral and anterior-posterior displacements (P=0.50 and 0.70, respectively). In conclusion, SV cranial displacement was influenced by HS lateral distribution of ≥1.00 cm in the upper two slices. Therefore, when the sigmoid colon or small bowel is depressed in rectovesical excavation and SV needs to be included in the target volume, HS insertion should be performed carefully.

Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer.

Ultrahypofractionated radiation therapy is increasingly used in the treatment of prostate cancer. High-dose-rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are representative methods of ultrahypofractionation. This study was performed to compare clinically applied treatment plans for patients who had been treated using HDR-BT vs. conventional or robotic SBRT. Calculated dose-volume indices between HDR-BT without a perirectal spacer (n=20), robotic SBRT without a spacer (n=40), and conventional (non-robotic) SBRT with a spacer (n=40) were compared. Percentages against the prescription dose regarding the planning target volume (PTV), bladder, rectum, and urethra were statistically compared. The D50% of the PTV with HDR-BT (140.5%±4.9%) was significantly higher than that with robotic or conventional SBRT (116.2%±1.6%, 101.0%±0.4%, p<0.01). The D2cm3 of the bladder with HDR-BT (65.6%±6.4%) was significantly lower than those with SBRT (105.3%±2.9%, 98.0%±1.3%, p<0.01). The D2cm3 of the rectum with HDR-BT (60.6%±6.2%) was also significantly lower than those with SBRT (85.1%±8.8%, 70.4%±9.6%, p<0.01). By contrast, the D0.1cm3 of the urethra with HDR-BT (117.1%±3.6%) was significantly higher than those with SBRT (100.2%±0.7%, 104.5%±0.6%, p<0.01). HDR-BT could administer a higher dose to the PTV and a lower dose to the bladder and rectum, at the cost of a slightly higher dose to the urethra compared with SBRT.

A Space Expander of Laparoscopic Rectal Cancer Surgery for Overweight or Obese Patients.

Laparoscopic rectal cancer surgery (LRCS) has become a preferred approach for its minimal invasion and fast postoperative recovery. But it is challenging for the tumors of the middle and lower rectum, especially for overweight or obese patients. We present a space expander of laparoscopic rectal cancer surgery, which is a simple tool to widen the perirectal space, as to facilitate the procedure of total mesorectal excision (TME) during the rectal cancer surgery. It has several advantages of lower demand for an assistant, less risk of surgical complications and good feasibility. It is designed as a cylindrical shape, and it is the first invented device to help surgeons safely perform accurate TME on overweight or obese patients during LRCS. With this method, we are able to dissect the rectal wall circumferentially in a safe and quick way. Our previous pig experiments indicated that the learning curve for this technique was as short as 10minutes. Further clinical trials will be conducted on its efficacy and safety in the future.

Hyaluronic acid spacer in prostate cancer radiotherapy: dosimetric effects, spacer stability and long-term toxicity and PRO in a phase II study

BackgroundPerirectal spacers may be beneficial to reduce rectal side effects from radiotherapy (RT). Here, we present the impact of a hyaluronic acid (HA) perirectal spacer on rectal dose as well as spacer stability, long-term gastrointestinal (GI) and genitourinary (GU) toxicity and patient-reported outcome (PRO).MethodsIn this phase II study 81 patients with low- and intermediate-risk prostate cancer received transrectal injections with HA before external beam RT (78 Gy in 39 fractions). The HA spacer was evaluated with MRI four times; before (MR0) and after HA-injection (MR1), at the middle (MR2) and at the end (MR3) of RT. GI and GU toxicity was assessed by physician for up to five years according to the RTOG scale. PROs were collected using the Swedish National Prostate Cancer Registry and Prostate cancer symptom scale questionnaires.ResultsThere was a significant reduction in rectal V70% (54.6 Gy) and V90% (70.2 Gy) between MR0 and MR1, as well as between MR0 to MR2 and MR3. From MR1 to MR2/MR3, HA thickness decreased with 28%/32% and CTV-rectum space with 19%/17% in the middle level. The cumulative late grade ≥ 2 GI toxicity at 5 years was 5% and the proportion of PRO moderate or severe overall bowel problems at 5 years follow-up was 12%. Cumulative late grade ≥ 2 GU toxicity at 5 years was 12% and moderate or severe overall urinary problems at 5 years were 10%.ConclusionWe show that the HA spacer reduced rectal dose and long-term toxicity.

Clinical value of normal saline injection for expansion of the anterior perirectal space during prostate cryoablation.

The objective of this study is to describe the technique and evaluate the clinical value of normal saline (NS) injection for expanding the anterior perirectal space during prostate cryoablation for prostate cancer (PCa) patients. PCa patients who received cryoablation between August 2014 and December 2019 were enrolled, and the technique of NS injection was adopted. The complications were evaluated. The prostate-specific antigen (PSA) nadir and biochemical progression-free survival (bPFS) were measured in localized PCa patients who received cryoablation as the primary treatment. A total of 159 PCa patients were included. Among 147 patients with the data of anterior perirectal space, the median (interquartile range [IQR]) distance of estimated iceball edge beyond the prostatic capsule was 8.3 (7.0-10.0) mm. No cases of urethrorectal fistula were reported; 29 patients developed urinary retention and 25 patients presented scrotal edema. All complications below Clavien-Dindo grade IIIb disappeared within 7 weeks after surgery. Urinary incontinence was reported in 6 patients. Among localized PCa patients, the median (IQR) follow-up time was 56.5 (36.0-73.5) months. The estimated 5-year bPFS was 82.3% overall, 82.8% for low-to intermediate-risk PCa patients, and 82.1% for high-risk PCa patients. For 52 patients received cryoablation alone, the median (IQR) PSA nadir was 0.147 (0.027-0.381) ng/mL. The technique of NS injection for expanding the anterior perirectal space during cryoablation surgery could avoid urethrorectal fistula and might benefit localized PCa patients with lower PSA nadir and longer bPFS.

Management of Hemorrhage during Dilation and Evacuation by Mid-Procedure Laparoscopic Uterine Artery Ligation

<h3>Study Objective</h3> To present a video demonstrating a multidisciplinary technique for managing hemorrhage during a dilation and evacuation (D&E) via intraoperative consult to minimally invasive gynecologic surgery (MIGS) and laparoscopic uterine artery ligation <h3>Design</h3> Case report. <h3>Setting</h3> Operating room at tertiary care center. <h3>Patients or Participants</h3> 37-year-old gravida 5 para 4 at 22 weeks gestation. <h3>Interventions</h3> A video demonstration of a laparoscopic, bilateral uterine artery ligation with pregnancy in situ to control mid-procedure hemorrhage. After initiating the D&E procedure, brisk bleeding was encountering with an estimated blood loss of 1600 mL within minutes. Options for controlling the hemorrhage were limited, as uterotonics or balloon tamponade were not possible with the pregnancy still in situ, and interventional radiology was not available for uterine artery embolization. An urgent, intraoperative consultation to MIGS was placed. A diagnostic laparoscopy was performed to evaluate for placenta accreta, uterine perforation, or other injury. No hemoperitoneum or defect was noted, however given ongoing heavy vaginal bleeding and potential need for a hysterectomy, the decision was made to proceed with uterine artery ligation prior to completion of the D&E procedure. Starting on the left side, the round ligament was incised, and the retroperitoneum was entered. The perirectal space was developed using the horizontal push-spread technique The uterine artery was skeletonized and ligated at its origin with a vascular clip. This was repeated on the contralateral side. Excellent hemostasis was noted, and the D&E was completed under laparoscopic guidance. <h3>Measurements and Main Results</h3> N/A. <h3>Conclusion</h3> Mid-procedure laparoscopic uterine artery ligation is a feasible option for controlling hemorrhage during second trimester dilation and evacuation when more traditional methods are not feasible or unavailable. A multidisciplinary, subspecialty approach to management of gynecologic complications can help optimize safe gynecologic procedures.

PP10 Presentation Time: 11:00 AM: Assessment of NASHA Spacer Symmetry for Prostate Radiation Therapy

<h3>Purpose</h3> NASHA (non-animal stabilized hyaluronic acid) is a spacer that can increase the separation between the prostate and anterior rectal wall prior to prostate radiation therapy (RT). Since there is no pre-defined time limit for NASHA spacer injection, physicians can precisely distribute the product within the peri-rectal space. Furthermore, the spacer is highly visible on T2-weighted MR, and generally visible on CT with optimized view settings. We conducted a randomized controlled trial evaluating whether a NASHA spacer improves rectal dosimetry among patients receiving hypofractionated RT (NCT 04189913). The purpose of the study is to evaluate the symmetry of a NASHA spacer among all patients who received the device on that study. <h3>Materials and Methods</h3> We analyzed data for 131 of 136 patients, who were randomized to and received a NASHA spacer on trial (5 datasets were unavailable at the time of analysis). All patients had pre-implant and post-implant CT/MR simulation. We developed an automated system for evaluating symmetry based on a previously published method (Fischer-Valuck, PRO, 2017). Briefly, prostate, rectum and spacer contours that had been prospectively validated by a core laboratory were downloaded. From the prostate center-of-mass, we defined axial slices at mid-gland, 1-cm superior, and 1-cm inferior. For each axial slice, we calculated the center of the spacer (spacer width center) along the transverse axis. Axial slice symmetry scores were assigned based on the distance between the spacer width center and the prostate midline (1 = distance within 1 cm of midline (symmetric), 2L/2R = distance between 1-2 cm from midline, 3L/3R = distance more than 2 cm from midline). Patient-level symmetry scores were assigned based on the number of slices with an asymmetric distribution (1 = none, 2 = 1 of 3 slices with axial score of 2L/2R, 3 = 2 of 3 slices with axial score of 2L/2R, 4 = all 3 slices with axial score of 2L/2R). <h3>Results</h3> The percentages of patients with an axial slice symmetry score of 1 (symmetric) at mid-gland, superior, and inferior planes, were 97%, 98%, and 98%, respectively (see Figure). Following the Fischer rubric, planes without gel were omitted (N=2 mid-gland, N=2 superior and N=9 inferior planes). The percentage of patients with patient-level symmetry scores of 1, 2, 3 and 4, were 95.4%, 2.3%, 1.5%, and 0.8% respectively. <h3>Conclusions</h3> Over 95% of NASHA spacers placed in this prospective trial demonstrated patient-level symmetry. These results suggest that NASHA may also improve rectal dosimetry for prostate brachytherapy. Further study is ongoing to correlate the dosimetry and clinical outcomes to implant quality for these patients.

Hyaluronic Acid Spacer in Prostate Cancer Radiotherapy: Dosimetric Effects, Spacer Stability and Long-Term GI Toxicity and PRO in a Phase II-Study

<h3>Purpose/Objective(s)</h3> Rectal side effects are common after radiotherapy (RT) to the prostate. To reduce side effects, perirectal spacers to separate the prostate from the rectum, thereby reducing the rectal dose, may be beneficial. This study presents the impact of a hyaluronic acid (HA) perirectal spacer on the rectal dose, MRI evaluation of spacer thickness during RT and a five-year follow-up of patient-reported outcome (PRO) and gastrointestinal (GI) toxicity. <h3>Materials/Methods</h3> 81 patients (<75 years) with low- (T1c-T2 and Gleason ≤ 6 and PSA < 10) and intermediate-risk prostate cancer (PC) (T1c-T3a with 1 or 2 of the risk factors T2c-T3a or Gleason ≥ 7 or PSA ≥ 10) received transrectal injections with HA (Macrolane VRF 30, Q-Med/Galderma, Uppsala, Sweden) as a perirectal spacer in this phase II-study between 2010-2016. External beam RT, 78 Gy in 39 fractions, were given with 3DCRT or IMRT using fiducial markers as image guidance. MRI was performed before (MR0) and after HA injection (MR1), at the middle (MR2) and at the end of RT (MR3). GI toxicity was assessed up to five years according to the RTOG scale. PRO GI side effects were collected using The Swedish national prostate cancer registry (NPCR) and PCSS questionnaires. <h3>Results</h3> HA thickness was measured at the prostate base, middle and apex for 52 of 81 patients. Exclusion due to failed HA-injections (6), missing MRT or RT data (17), larger PTV margins (5) and other treatment (1). HA thickness and CTV-Rectum spaces in apex- and middle- position was decreasing from MR1 to MR2/MR3. No significant differences were found between MR2 and MR3. Overall, HA thickness in the middle position had the strongest significant correlation (Spearman's rho ρ= 0.70) to CTV-Rectum spacing. There was a significant decrease in the relative rectum volume that received 70.2 Gy (V90%) from MR0 (8.6 ±5.7 %) to MR1 (2.7± 4.1 %). There was a significant increase from MR1 to MR2 (6.0±9.0%) and no significant difference between MR2 and MR3 (5.7±7.9 %) in rectum V90%. All with significance p<0.05. At the end of RT 17 patients (25.8%) experienced grade 1 GI toxicity, and four patients (6.1%) grade 2. At six months the proportion of grade 2 and 3 GI toxicity was 3.2%, and 1.6%. After 18 months no grade ≥ 2 GI toxicity was observed. The estimated cumulative late grade ≥ 2 GI toxicity rate at 5 years was 4.8 %. PRO moderate or severe overall bowel problems at start RT, end of RT and 5 years were 0%, 17.6% and 12.2% with a mean score of 14.6 (scale 0–100; higher value refers to more symptoms/worse function) at 5 years. <h3>Conclusion</h3> After HA-spacer, the relative rectum volumes receiving 70.2 Gy (V90%) were significantly lower. V90% increased significantly from MR1 to MR2/MR3, but still a significant reduction from MR0. The 5-year cumulative risk of late GI toxicity grade >1 was low whereas 12 % reported moderate/severe GI-bothers in the PRO at 5 years.

Can Perirectal Spacing Help Reduce GI Toxicity in Patients Undergoing Post-Prostatectomy Radiotherapy?

<h3>Purpose/Objective(s)</h3> To report single institutional feasibility of recto-vesical hyaluronic acid or hydrogel spacer insertion for patients undergoing post prostatectomy radiotherapy (PPRT). <h3>Materials/Methods</h3> Spacer insertion was considered in patients referred for PPRT following an intra or interfascial radical prostatectomy who had no radiological evidence of local recurrence (based on prostate specific membrane antigen positron emission tomography). The spacer was inserted into the perirectal fat between the bladder and anterior rectal wall using a transperineal approach under transrectal ultrasound guidance. Two gold seed fiducial markers were also inserted at the level of the vesico-urethral anastomosis for image guided radiation therapy as per institutional practice. Pre and post spacer computerized tomography planning scans, together with post spacer magnetic resonance imaging scans, were acquired for dosimetric comparison. The prostate bed clinical target volume (CTV) was delineated according to Australian guidelines and the CTV was uniformly expanded by 7mm to create the planning target volume (PTV). The prescribed dose to the prostate bed was 70.2Gy in 1.8 Gy fractions using volumetric arc radiation therapy. The PTV and rectal dosimetry for the two sets of planning scans (PTV 7mm/pre spacer and PTV 7mm/post spacer) were compared. <h3>Results</h3> Sixty-one patients were recruited between 9/18 to 10/21. Fifty-eight patients successfully underwent rectal spacer insertion without postoperative complications. We did not attempt spacer insertion in 3 patients as we were unable to hydrodissect the perirectal fat plane. Only 33 patients had pre spacer planning scans available for dosimetric comparison. The distance between the bladder and rectal wall was increased from ≤1mm to a median of 11mm (9-13) at its greatest extent. The rectal volume for all patients (N=61) receiving 42.2Gy (rV60%), 49.1Gy (rV70%), 56.2 Gy (rV80%), 63.2Gy (rV90%) and 70.2Gy (rV100%)] were 28.1%, 23%, 17.9%, 12.5% and 3.8% respectively. With spacing, a statistically significant reduction was seen on all rectal volume end points from rV60% to rV100% in the 33 patients with both pre and post planning scans (see Table 1). The median follow up was 10.5 months (3-31). The risk of any grade acute GI toxicity was 28% (grade 1 26% and grade 2 2%). The risk of late GI toxicity was 7% (all grade 1 proctitis). <h3>Conclusion</h3> More than 90% of our selected PPRT patients were able to achieve recto-vesical separation, with no surgical complications, resulting in a 43.7% reduction in rV90%. The reduction in acute and late grade 2 GI toxicity is of notable significance, albeit with short follow up. Table 1 Pre and Post Spacer Rectal Dosimetry

The Use of HA as Rectal Spacer in Prostate Cancer Patients Undergoing Hypofractionated RT: An Australian Experience

<h3>Purpose/Objective(s)</h3> To report the feasibility, post-operative complications and recto-prostatic separation achieved with hyaluronic acid (HA) inserted into the perirectal fat before definitive prostate radiotherapy (RT). <h3>Materials/Methods</h3> Fifty-seven patients with clinical stage T1-3 prostate cancer underwent transrectal ultrasound guided transperineal insertion of fiducial markers and HA into the perirectal space before volumetric arc RT between 7/2020 to 7/2021. Post insertion computerized tomography (CT) and magnetic resonance imaging (MRI) scans were obtained for treatment planning. HA feasibility, safety and recto-prostatic separation were assessed. The prescribed dose to the planning target volume (PTV) ranged from 60-62Gy in 20 fractions. <h3>Results</h3> The mean age was 74.7 years. The median PSA was 8.1 [Interquartile range (IQR)6.2-10.0]. The majority of patients had ISUP 2 adenocarcinoma (60%). The rest had ISUP 1 (11%) and ISUP 3 (30%). The disease risk was staged as early in 11%, favorable intermediate in 30%, unfavorable intermediate in 58% and high in 2%. Androgen deprivation therapy was delivered in 63%. HA insertion was completed with a 100% success rate. This was rated as ‘easy' to ‘very easy' 100% of the time. There were no device related complications, rectal perforation, serious bleeding, infections or allergic reactions. The mean prostate size was 43cc (IQR 30-55cc). Recto-prostatic separation at the base (measured 5mm below the prostate base), mid gland and apex (measured 5mm above the prostate apex) were 12mm (0.2), 11mm (0.2) and 0.9mm (0.1) respectively. The HA was also symmetrically placed in breadth at the mid gland in all patients. The mean rectal volume receiving 53Gy (rV53) was 3.2% (IQR 1.3-5.5) for patients receiving 60-62Gy. The median follow up was 13.5 months (IQR 9.5-17.5). The risk of any acute GU toxicity was 81%. The majority had grade 1 GU toxicity at 67% with urinary frequency, urgency and obstruction being the commonest reported side effects. The risk of any grade 2 GU toxicity was 14% with urinary obstruction (13%) and urgency (7%). The risk of any acute GI toxicity was 2%. Only 1 patient developed grade 1 GI toxicity with diarrhea. The risk of any late GU toxicity was 43%. The majority had grade 1 GU toxicity at 32% with urinary frequency, urgency and obstruction. The risk of any grade 2 GU toxicity was 11% with urinary obstruction (5%), urgency (5%) and incontinence (2%). The risk of any late GI toxicity was 2%. Only 1 patient had grade 1 GI toxicity with diarrhea. <h3>Conclusion</h3> HA was successfully inserted in all patients and was well tolerated. Recto-prostatic separation was symmetrical in length from the base to the apex and in breadth at the midgland. The risk of developing any acute GI toxicity was minimal at 2% with the use of HA. In addition, the risk of late GI toxicity was 2%, albeit with short follow up.

Hyaluronic acid rectal spacer in EBRT: Usability, safety and symmetry related to user experience

ObjectivesTo report on the usability, safety, symmetry, and effectiveness of hyaluronic acid (HA) injected between the prostate and the rectum for patients undergoing treatment for prostate cancer with external beam radiotherapy (EBRT), and present a novel definition of rectal spacer symmetry that is reproducible and independent of patient anatomy. Patients and Methods102 consecutive patients with clinical stage of T1c-3b prostate cancer underwent general anaesthesia for fiducial marker insertion and injection of HA into the perirectal space before EBRT. HA safety, symmetry, separation, and usability based on user experience were assessed. ResultsHA insertion was completed with a 100% success rate independent of user experience, rated as ‘easy’ or ‘very easy’ in all cases. There were no postoperative complications reported. The mean (SD) recto-prostatic separation for all patients at the base, midgland and apex were 12 (±2) mm, 11 (±2) mm, and 9 (±1) mm respectively. The mean sagittal length of the implant was 43 (±5) mm. The implant was rated as symmetrical in 98% of cases. The mean rV70Gy was 1.6% (IQR 0.8-3.3%) for patients receiving 78-80Gy. The mean rV53Gy was 2.8% (IQR 1.2-4.8%) for patients receiving 60-62Gy. The median prostate size was 43.5 cc (IQR 32-57). ConclusionInjection of HA was able to achieve highly symmetrical recto-prostatic separation, with new users able to produce excellent separation, particularly at the apex, achieving similar dosimetry outcomes as competent and experienced users. HA is safe, easy to use, and significantly reduced mean rV70Gy and rV53Gy compared to non-spacer patients.