Question: A 70-year-old man with a history of obstructive sleep apnea, mitral valve repair, coronary artery disease, hyperlipidemia, and nephrolithiasis was scheduled to start stereotactic body radiation therapy (SBRT) for intermediate-risk prostate cancer when he developed an episode of bright red blood per rectum. At baseline, he denied dysuria, hematuria, incontinence, rectal bleeding, diarrhea, and history of colonic polyps. Before radiation therapy, he received androgen deprivation therapy and underwent transrectal ultrasound-guided placement of SpaceOAR, a commercially available, perirectal polyethylene glycol hydrogel approved by the US Food and Drug Administration. The patient experienced generalized pelvic pain a few days after the procedure which resolved without intervention. On postprocedure day (PPD) 15, magnetic resonance imaging (MRI) showed limited rectal wall serosal infiltration by SpaceOAR hydrogel (Figure A). On PPD 26, the patient had an episode of bright red blood per rectum. He did not have fevers, chills, nausea, vomiting, abdominal pain, rectal pain, urgency, diarrhea, constipation, melena, dysuria, and hematuria. Laboratory data collection was deferred but he was referred for urgent flexible sigmoidoscopy which showed only mild erythema on PPD 30 (Figure B). Radiation therapy was delayed owing to this finding. Repeat sigmoidoscopy 4 weeks later showed a 1.5-cm cratered ulcer with friable edges on the anterior wall of the rectum, approximately 5 cm from the anal verge (Figure C). What is your next step in diagnosis and management? What is the suspected mechanism of injury for this lesion? Look on page 1177 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and images in GI. Cross-sectional imaging, T2-weighted MRI can be used to assess extent of rectal ulceration, and evaluate for fistula formation. Compared with next-generation radiopaque SpaceOAR VUE hydrogel, conventional SpaceOAR hydrogel used in this case is not visible on CT imaging. The mechanism of injury for the cratered ulcer may be migration of the hydrogel needle with possible rectal wall ischemia from excessive tension of the hydrogel. An MRI of the pelvis on PPD 66 showed T2 hyperintense signal abnormality concerning for an inflamed fistula extending from the mid anterior rectal wall inferiorly to the level of the urogenital diaphragm (Figure D). The lesion was associated with the SpaceOAR hydrogel and in close proximity to the urethra. At the time of diagnosis, the patient did not experience symptoms suggesting infection, and thus he was monitored closely with serial sigmoidoscopies. His planned prostate SBRT was postponed until resolution of the rectal ulcer and fistulous tract. He continued on androgen deprivation therapy. Subsequent sigmoidoscopies showed eventual healing of the ulceration on PPD 108 and stable healing on PPD 150 (Figure E). An MRI of the pelvis at 23 weeks from SpaceOAR application showed complete resolution of the fistulous tract. The patient did not experience further episodes of rectal bleeding. He completed SBRT to the prostate and seminal vesicles in 5 fractions approximately 30 weeks after SpaceOAR placement. At the University of California San Francisco, radiation oncologists obtain a prostate MRI in patients after placement of SpaceOAR hydrogel to evaluate for rectal wall injury and to finalize radiation planning. If the MRI demonstrates any evidence of rectal wall injury, the patient is referred for sigmoidoscopy to identify ulcers or associated mucosal injury. The radiation plan is postponed until resolution of rectal wall injury to avoid the effects of radiation on wound healing that may lead to a persistent ulcer or permanent fistula. Toxicity from radiation to the prostate affects quality of life, including urinary function, gastrointestinal symptoms, and sexual health effects. Peri-rectal spacers such as the SpaceOAR system (Augmenix, Inc., Bedford, MA) are increasingly used to decrease radiation dose to the rectum and to reduce risk of radiation-related bowel toxicity.1Armstrong N. Bahl A. Pinkawa M. et al.SpaceOAR Hydrogel Spacer for reducing radiation toxicity during radiotherapy for prostate cancer. a systematic review.Urology. 2021; 156: e74-e85Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar SpaceOAR is made of an absorbable polyethylene glycol hydrogel that is injected via transperineal needle under transrectal ultrasound guidance. The procedure involves hydrodissection of the space between Denonvilliers’ fascia and the anterior rectal wall, followed by mixing of the polymerizing agent and hydrogel monomers and injection of the mixture into the dissected perirectal space. Immediately after injection, the hydrogel polymerizes and solidifies, increasing the separation between the prostate and rectum. The hydrogel remains stable for approximately 12 weeks, after which it is degraded by hydrolysis, absorbed, and renally excreted. Other biomaterials such as hyaluronic acid, human collagen, and absorbable biodegradable balloons have been investigated as alternatives to SpaceOAR, some of which are expected to enter the North American market soon.1Armstrong N. Bahl A. Pinkawa M. et al.SpaceOAR Hydrogel Spacer for reducing radiation toxicity during radiotherapy for prostate cancer. a systematic review.Urology. 2021; 156: e74-e85Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Complications from SpaceOAR hydrogel are rare. However, those documented in case studies and trials include anterior rectal ulcers, rectourethral fistula, and rectal abscess formation. An evaluation of the SpaceOAR Manufacturer and User Facility Device Experience database revealed 25 adverse events from 2015 to 2019, of which 7 patients experienced rectal wall erosion, rectal wall ulcer, or rectourethral fistula formation.2Aminsharifi A. Kotamarti S. Silver D. et al.Major complications and adverse events related to the injection of the SpaceOAR hydrogel system before radiotherapy for prostate cancer: review of the manufacturer and user facility device experience database.J Endourol. 2019; 33: 868-871Crossref PubMed Scopus (45) Google Scholar Other case studies have reported perineal abscess formation requiring drainage. Possible mechanisms of injury leading to these complications include mechanical injury by inadvertent injection of hydrogel into the rectal wall, ischemic injury from excessive tension of the tissue injected with hydrogel, and infection as a nidus for development of abscesses. In several cases, patients had completed radiation therapy ranging from EBRT to low-dose rate brachytherapy before experiencing symptoms, suggesting that radiation injury may play a role in these rare complications. The management of anterior rectal ulcers and perirectal fistulas tends to prioritize temporary suspension of radiation therapy to allow for mucosal healing and, in a few cases, hyperbaric oxygen therapy.3Kashihara T. Inaba K. Komiyama M. et al.The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report.BMC Urol. 2020; 20: 196Crossref PubMed Scopus (5) Google Scholar To date, antibiotics have not been consistently integrated into the management of rectal ulcers and perirectal fistulas unless systemic symptoms or concern for sepsis is noted on case reports. As rectal spacers are increasingly used as a tool to decrease radiation exposure to the rectum, more research is needed to mitigate rare complications and optimize patient selection and procedural techniques.