SpaceOAR Hydrogel Present 32 Weeks After Instillation Prevents Neobladder Creation in Patient Undergoing Robot-Assisted Laparoscopic Radical Cystoprostatectomy

Abstract

Background: The injection of hydrogel in between the anterior rectal wall and prostate protects the rectum from the radiation field in men undergoing radiotherapy for prostate cancer. Multicenter prospective trials have demonstrated safety of the material, and that liquefication and reabsorption of the material occur roughly 12 weeks after injection. Other studies have noted the presence of the hydrogel up to 24 weeks after injection and documented significant complications with its use. In this study we discuss a patient in whom hydrogel was discovered in the anterior rectal wall who was undergoing radical cystoprostatectomy 32 weeks after injection, and how this precluded creation of a neobladder.

Case Presentation: A 64-year-old Caucasian man with a history of diabetes mellitus and hypertension was diagnosed with unfavorable intermediate risk prostate cancer. He underwent injection of hydrogel followed by radiotherapy. He subsequently developed hematuria and carcinoma in situ and high grade T1 nonmuscle invasive bladder cancer were diagnosed. Thirty-two weeks later, he underwent robot-assisted radical cystoprostatectomy. The patient was originally planned for neobladder creation but intraoperative findings of persistent hydrogel in between rectum and prostate precluded this reconstruction and necessitated construction of an ileal conduit.

Conclusion: Urologists should be aware of the fact that SpaceOAR hydrogel can persist beyond the expected 12- to 24-week dissolution period. In a patient who requires a radical cystectomy, the persistent presence of that gel may preclude the creation of a neobladder. Preoperative imaging to identify persistence vs dissolution of the gel would facilitate better preoperative patient counseling.

Introduction and Background

Although definitive radiotherapy is an accepted treatment for localized prostate cancer, the dose-limiting toxicity is the toxicity to the rectum. The application of a physical spacer between the rectum and prostate is a well-recognized technique that mitigates rectal radiation toxicity.¹ Hyaluronic acid, human collagen, an inflatable balloon, or hydrogel are all materials that have been employed to create the desired effect.

The SpaceOAR system (Augmenix, Inc., Waltham, MA) is a synthetic polyethylene glycol hydrogel that is inserted transperineally under transrectal ultrasound (TRUS) guidance.² The injection of the gel between the anterior rectal wall and the prostate distances the rectum from the radiation field (Fig. 1A).³ Prospective multicenter studies have demonstrated that it is a safe and efficacious method to protect the rectum from radiation toxicity.¹ The hydrogel is meant to hydrolyze, liquefy, and become absorbed roughly 12 to 24 weeks after injection.³ Patients typically are able to receive all of their radiation treatments within this 24-week window. Significant complications can occur however with the migration of this material or its failure to reabsorb.⁴

FIG. 1.

(A) MRI showing SpaceOAR hydrogel placement.³ (B) Anterior rectal wall demonstrating erythema and inflammation after prostate radiation as well as bulge from persistent presence of SpaceOAR hydrogel. (C) CT scan of patient's abdomen/pelvis showing persistence of SpaceOAR hydrogel (arrow) 20 weeks after injection.

Case Presentation

A 64-year-old Caucasian man with a history of diabetes mellitus and hypertension was found to have unfavorable intermediate risk prostate cancer. The patient's prostate-specific antigen was 10.4 ng/dL and digital rectal examination revealed a smooth and symmetrical prostate. On TRUS, his prostate volume was measured to be 55 mL and biopsies demonstrated multifocal Gleason 4 + 3 as well as one area of high-grade prostatic intraepithelial neoplasia. After a lengthy discussion of the risks of surgery and radiation, the patient opted for curative radiation therapy and androgen deprivation therapy. He underwent transperineal injection of the SpaceOAR gel in our office 8 weeks after his initial prostate cancer diagnosis and proceeded with intensity-modulated radiation therapy. Four weeks after injection of the hydrogel while in the midst of radiation therapy, he was evaluated for acute onset gross hematuria with clot obstruction. Cystoscopy revealed papillary lesions at the dome of the bladder and he subsequently underwent bipolar transurethral resection of bladder tumor and intravesical instillation of gemcitabine. Pathology analysis revealed high-grade T1 disease and carcinoma in situ (CIS). Given the presence of unfavorable risk prostate cancer and high grade T1 nonmuscle invasive bladder cancer and CIS, this patient was discussed at our institutional tumor board and recommendation was made for early radical cystectomy. The patient was counseled about cystectomy and urinary diversion options and the decision was made to proceed with robot-assisted laparoscopic radical cystoprostatectomy with creation of neobladder.

We began this patient's surgery with the intention of creating a neobladder as was his clearly stated preference. However, upon entry into the peritoneal cavity with our Da Vinci Xi endoscope through the 8 mm periumbilical trochar, we saw thick mesenteric fat tethering the bowel and limiting the mobility of the small intestine down into the pelvis, making us skeptical of the feasibility of a neobladder. Upon inspection of the periprostatic tissue, it was noted that there was significant radiation-associated dysplastic tissue changes as well as a mass deep into Denonvier's fascia superior to the prostate gland that was concerning for rectal tumor. A digital rectal examination was performed that was notable for a nodular indurated prostate gland but normal rectal vault. The mass could not be palpated because of its deep position. We then realized that this was likely the patient's previously placed SpaceOAR hydrogel that had not fully absorbed despite it being injected 32.5 weeks before his surgery. To rule out a rectal tumor, we consulted colorectal surgery for an intraoperative colonoscopy, which was notable for inflammatory erythematous changes of the anterior rectal mucosa with a mass effect but was negative for rectal tumor (Fig. 1B).

At this time, significant discussion and thought was given to the possibility of proceeding with neobladder vs ileal conduit. Given the thick mesenteric fat making bowel mobilization difficult, the dysplastic changes from radiation in the deep pelvis, and the presence of persistent SpaceOAR hydrogel that may have obscured clean urethral margins upon excision of prostate, we elected to proceed with ileal conduit creation and abandon the neobladder possibility. The patient's wife was informed of our findings and she provided consent to proceed with ileal conduit. Postoperative discussions with our patient as to our reasoning, as well as early intervention and teaching by the ostomy nursing staff led to this patient coping with his ileal conduit well.

Surgical pathology analysis demonstrated organ-confined adenocarcinoma of the prostate, (stage pT2N0M0). Gleason scoring was not available given patient's history of radiation. Bladder pathology analysis demonstrated CIS and negative distal ureteral margins. He was readmitted to the hospital 3 weeks postoperatation for dehydration, which required an overnight hospital stay but he has not had any other postoperative complications.

Discussion

The safety profile of SpaceOAR is well documented in multicenter trials as is its tolerability by patients. In a phase III clinical trial, it was demonstrated that the majority of patients do not experience any sensation immediately after placement and only 10% of patients reported grade 1 application procedure-related adverse events (hematuria and hematospermia) or grade 2 events that required medication (bothersome lower urinary tract symptoms, hypotension).³ Furthermore, no adverse events were attributed to the hydrogel itself. However, the injection of hydrogel constitutes a procedure, and like most procedures, it is not without risk to patients. Other investigators have described rectal wall erosion, abscess formation, fistulization, anaphylaxis, and urosepsis.⁴ Interestingly, there is a paucity of data reviewing the effects of SpaceOAR gel as it pertains to surgery within or outside of the 12-week reabsorption window.

To our knowledge, this is the first report of a surgery performed in the pelvis of a patient with persistent SpaceOAR hydrogel present. Although a preoperative CT scan obtained at an outside hospital 20 weeks after injection demonstrated persistence of this hydrogel (Fig. 1C), our assumption was that the gel material would not still be present 12 weeks later at the time of surgery. In addition, there were inflammatory changes in the pelvis that were likely caused by recent external beam radiation, but the persistent SpaceOAR hydrogel may have contributed. Had we known the effects of persistent hydrogel or that it would still be present at the time of surgery, we may have counseled him toward the increasing likelihood of him receiving a conduit.

The subject as to why the hydrogel persisted in this particular patient well outside the expected timeframe for dissolution is cause for speculation. Whether it was related to the manner in which the operator injected the hydrogel or a result of the patient's milieu is unknown. One possible explanation is that the reported average timeframe for dissolution of 3 to 6 months is an underestimation. Additional research is needed to answer this question.

Conclusion

The safety and tolerability of SpaceOAR hydrogel are acceptable for widespread use. However, urologists should be aware that this substance may persist beyond the advertised 12- to 24-week dissolution timeframe. Although this may be inconsequential for the average patient with prostate cancer, in a patient who also necessitates a radical cystectomy, the presence of this substance may preclude the creation of a neobladder. Cross-sectional imaging within 1 to 2 weeks of surgery may be necessary to definitively establish dissolution of the hydrogel to more appropriately counsel patients in the preoperative setting.

Abbreviations Used

CI

computed tomography

CIS

carcinoma in situ

MRI

magnetic resonance imaging

TRUS

transrectal ultrasound

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Cite this article as: Balen A, Sobel D, Elsamra S, Golijanin D (2020) SpaceOAR hydrogel present 32 weeks after instillation prevents neobladder creation in patient undergoing robot-assisted laparoscopic radical cystoprostatectomy, Journal of Endourology Case Reports 6:4, 442–444, DOI: 10.1089/cren.2020.0088.