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    Interventional procedure overview of biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer

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    Safety summary

    Procedure related complications

    In the systematic review and meta-analysis of 7 studies, authors state that procedural complications(defined as inability to inject the hydrogel spacer into the perirectal space or any complication, regardless of severity, occurring during the procedure) were infrequent and reported inconsistently (Miller 2020).

    The RCT included within several reviews reported mild and transient procedural adverse events (perineal discomfort and others, grade 1 to 2) in 10% patients in hydrogel spacer group. Grade 2 events (treated with medication) included mild lower urinary tract symptoms and hypotension, and moderate perineal pain. Fewer patients with a spacer had rectal pain (3% compared with 11% in control group, p=0.02). Hydrogel rectal infiltration during the procedure was reported in 6% (n=9) patients. Inadvertent needle penetration of the rectal wall (needing termination of the procedure) and hydrogel injected beyond the prostate were reported in 1 patient each. There were no grade 3 to 4 related adverse events or deaths (Mariados 2015).

    In the systematic review of 13 studies (n=671 patients with hydrogel spacer versus 537 patients without a spacer before prostate cancer brachytherapy), some procedure-related complications were reported in the hydrogel spacer groups (in 8 of the studies). These included:

    • rectal ulcer 2 months after hydrogel injection (causing frequent rectal bleeding, mucus discharge and bowel movements that resolved without intervention by 3 months) in a case report of 1 patient (Teh 2014),

    • perineal pain (that resolved without intervention within 1 week) in 3 patients,

    • sensation of pressure or fullness in the rectum (that resolved by 3 months with medication) in 1 patient,

    • sudden need for defecation (that resolved by 3 months with medication) in 1 patient,

    • infection (bacterial prostatitis after biopsies in 2 patients and epididymitis in 1 patient, which resolved after adjusting antibiotic prophylaxis),

    • rectal perineal abscess (in 1 patient after 1 month, needed incision, drainage and antibiotics),

    • severe proctitis (in 1 patient),and fistulas needing diverting colostomy (in 2 patients),

    • other complications such as rectal discomfort (n=7), bleeding (n=2), and diarrhoea were reported in 1 study of 74 patients with hydrogel (Taggar 2018) (Vaggers 2021).

    A review of complications of hydrogel spacer injections in the Manufacturer and User Facility Device Experience (MAUDE) database reported 22 unique reports discussing 25 patient cases (from January 2015 to March 2019), with an increasing number of reports each year up to 2019. The reported complications included:

    • venous injection in 3 (no sequelae),

    • tenesmus with air in rectal wall in 1 (no sequelae),

    • rectal wall erosion in 1 (no sequelae),

    • purulent drainage from perineum in 1 (needing antibiotics),

    • acute pulmonary embolism in 4 (needing anticoagulant),

    • perineal abscess in 3 (needing drainage), proctitis in 1 (needing colostomy), rectal ulcer and haemorrhage in 1 (needing surgery),

    • rectourethral fistula in 4 (needing diverting colostomy),

    • perirectal fistula in 1 (needing surgical intervention),

    • urinary tract infection and prostatic abscess in 1 (needing drainage),

    • perineal abscess and subsequent death from alcoholic cardiomyopathy in 1, severe urosepsis in 1 (needing ICU admission),

    • severe anaphylaxis in 1, dizziness and nausea post-procedure leading to unresponsiveness and

    • death in 1 (the cause of death was unclear) (Aminsharif 2019).

    Another recent review of complications of hydrogel spacers in the MAUDE database reported 85 unique reports (from 2015 to 2020). Of these 69% (59/85) events were grade 3, 4, or 5. 24% were grade 4 events, including colostomy (n=7) anaphylactic shock (n=2), rectal wall injection, pulmonary embolism requiring hospital admission (n= 5), and recto-urethral fistula (n= 8). One death was reported (Hall 2021).

    Inadvertent injection of hydrogel into the rectal lumen resulting in focal rectal mucosal necrosis and bladder perforation was reported after the procedure in 1 patient in a case series of 52 patients. This resolved with no sequelae (Uhl 2014, Song 2013). The same study included in the meta-analysis reported 1 case of inadvertent injection into the rectal lumen without adverse sequelae (Miller 2020).

    A case series of 27 patients with ERB (Gez 2013) included in the HTA report by EUnetHTA reported

    • acute urinary retention (needed catheterisation, which resolved within a few hours) in 12% (3/26) of patients during balloon insertion and in 1 patient during radiotherapy.

    • Dysuria and nocturia (grade 1 to 2) was reported in 12% (3/26) of patients during balloon insertion and in 65% (15/23) of patients during radiotherapy.

    • Penile bleeding was reported in 1 patient during balloon insertion. Further details were not reported.

    • Other events reported during radiotherapy in the same study included diarrhoea in 17% (4/23) of patients, mild proctitis in 8% (2/23) of patients, and in 1 patient each, blood in the faeces, constipation, erectile dysfunction, itching, fatigue and decreased urine flow (NIPHNO 2021).

    Haematoma developed behind the bladder in 1 patient with a moderate platelet count (within hours after injection) in a case series of 36 patients injected with a hyaluronic acid spacer. This was removed by laparotomy (Chapet 2015).

    In the systematic review of 11 studies, a case series of 11 patients injected with collagen implant during IMRT reported that 3 patients had self-limiting light rectal pressure.1 patient needed temporary catheterisation for acute urinary retention (presumed to be secondary to pudendal nerve blocking) (Mok 2014).

    Anecdotal and theoretical adverse events

    In addition to safety outcomes reported in the literature, professional experts are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never happened).

    For this procedure, professional experts listed the following anecdotal adverse events: intraprostatic infiltration of gel, urinary retention, hydrogel not solidifying, loss of implant (user preparation error when the implant deployed whilst being prepared for insertion). They described that "there is a theoretical possibility that spacer insertion could cause displacement of extracapsular prostate cancer leading to reduced efficacy of radiotherapy".