Rectal wall infiltration with hyaluronic acid based rectal spacer for prostate cancer and its reversal.

Abstract

Introduction and objectives: Radiation therapy for prostate cancer may cause gastrointestinal (GI) toxicity as the rectum is an organ at risk. Stabilised hyaluronic acid (sHA) has recently been approved for use as a rectal spacer and reduces GI toxicity in this setting. It has several advantages, including its reversibility using hyaluronidase. This is particularly beneficial in cases of rectal wall infiltration (RWI). The use of non-reversible rectal spacers may lead to severe adverse outcomes such as mucosal ulceration, pelvic abscess and recto-prostatic fistula after RWI. As such, we aim to assess the outcomes of inadvertent RWI by sHA rectal spacers. Method(s): We conducted a retrospective analysis of prostate cancer patients who developed RWI after sHA rectal spacer insertion between 2021 and 2024 across five Australian hospitals. Data included patient characteristics, RWI grades and volume, management strategies (reversal vs observation), and radiation therapy delays and toxicities. Spearman correlation assessed the relationship between sHA volume and RWI grades. Mann-Whitney U tests evaluated associations between RWI volume or Fischer-Valuck grade and the decision of reversal procedures, as well as the impact of RWI volume on radiation therapy delays. ROC analysis identified RWI volume cutoffs predictive of therapy delays. Result(s): A total of 16 prostate cancer patients were identified to have RWI after sHA spacer insertion. The grade of RWI as defined by Fischer Valuck criteria were as follows: Grade 1, N = 5; Grade 2, N = 6; and Grade 3, N = 5. The median volume of misplaced sHA was 2.8 cc from an average total of 9 cc used. No post procedural GI symptoms were reported. A sigmoidoscopy was performed in 12 patients including all 5 with grade 3 RWI, and all of these showed intact rectal mucosa. Seven patients underwent targeted reversal procedures while 9 patients were monitored. Of those who underwent reversal procedures, the median (and mean) volume of misplaced hyaluronic acid is 4 mL (3.8 mL), compared to 1.5 mL (2.1 mL) in those who did not undergo reversal (Mann-Whitney Utest, P = 0.1). All 7 who underwent reversal with hyaluronidase were successful. No post reversal complications were reported. One patient underwent successful reinsertion of sHA following reversal. Initiation of radiation therapy was delayed in 11 cases by a median of 3.2 months. All patients completed their RT as planned. No acute grade 2 or higher GI toxicity was reported in any of the 16 patients. ROC analysis indicated that a 3 mL RWI volume had optimal sensitivity and specificity for predicting delays. Conclusion(s): This study presents the first evidence for the safety of sHA rectal spacer in cases of RWI. sHA rectal spacers are generally safe, but careful monitoring and individualised management are essential for optimising outcomes in prostate cancer treatment.