This section describes efficacy outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
Only evidence on CE‑marked spacers has been considered and these have only been used with studies of external-beam radiation therapy.
4.1 In a prospective multicentre randomised controlled trial (RCT) of 222 patients with prostate cancer comparing hydrogel spacer injection (hydrogel, n=148) with no spacer injection as control (n=72) during image-guided intensity-modulated radiation therapy (IG‑IMRT), spacer placement success (defined as hydrogel present in the perirectal space) was reported in 99% (146/148) of patients in the spacer group. In a case series of 27 patients with a biodegradable balloon inserted for prostate rectum separation during radiotherapy, balloon placement success was reported in 96% (26/27) of patients.
4.2 In the prospective multicentre RCT of 222 patients, perirectal space (defined as the distance between the posterior prostate capsule and anterior rectal wall on axial mid‑gland T2‑weighted MRIs) after hydrogel insertion was 1.26±0.39 cm in the spacer group and 0.16±0.20 cm in the control group respectively (no statistical significance reported). In the case series of 27 patients, the distance between the prostate and rectum increased from a mean of 0.22±0.20 cm to 2.47±0.47 cm after balloon insertion. The distance remained constant throughout radiotherapy (2.47±0.47 cm and 2.41±0.43 cm).
4.3 In the prospective multicentre RCT of 222 patients, acute rectal toxicity was similar between the spacer and control groups (p=0.525), as was urinary tract toxicity (p=0.488). There was statistically significantly less rectal toxicity at 3 to 15 months in patients with a spacer (2% of patients: rectal bleeding, rectal urgency and proctitis, each in 1 patient) compared with patients in the control group (7% of patients: rectal bleeding in 3, rectal urgency in 1 and grade 3 proctitis in 1; p=0.04). The 3‑year incidence of rectal toxicity higher than grade 1 (2.0% compared with 9.2%; p=0.028) and higher than grade 2 (0% compared with 5.7%; p=0.012) was statistically significantly lower in the spacer group than control group. Urinary toxicity of higher than grade 1 was also lower in the spacer arm (4% compared with 15%; p=0.046), with no difference in higher than grade 2 urinary toxicity between the groups (7% compared with 7%; p=0.7). In a comparative case series of 78 patients comparing hydrogel spacer (n=30) with biodegradable balloon spacer (n=29) and no spacer (n=19), there were no statistically significant differences in acute toxicity between spacer and control groups 3 months after radiotherapy for any genitourinary, gastrointestinal or combined grade 2 toxicities.
4.4 In the prospective multicentre RCT of 222 patients, there was a statistically significant reduction in mean rectal dose volume within the 70 Gy isodose in patients in the spacer group (from baseline, 12.4% to 3.3% after spacer injection, p<0.001) compared with patients in the control group (from baseline, 12.4% to 11.7%). In the comparative case series of 78 patients, there was a statistically significant reduction in rectal dose in the balloon spacer group (by 27.7%, p=0.034). However, there was an average volume loss of more than 50% during the full course of treatment of 37 to 40 fractions; the volume of hydrogel spacers remained fairly constant.
4.5 In the prospective multicentre RCT of 222 patients, at 15‑month follow‑up, 12% of patients in the spacer group and 21% of patients in the control group reported a 10‑point decline (p=0.087) in bowel quality-of-life scores (assessed using the Expanded Prostate Cancer Index Composite self-assessment questionnaire). Bowel quality of life consistently favoured the spacer group from 6 months (p=0.002), with a 5.8‑point difference at 3 years (p<0.05) meeting the threshold for a minimally important difference (MID, 5 points). At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel quality of life (5‑point decline: 41% compared with 14%; p=0.002; odds ratio [OR] 0.28, 95% confidence interval [CI] 0.13 to 0.63). At 3‑year follow‑up, the control group had a 3.9‑point greater decline in urinary quality of life compared with the spacer group (p<0.05), but the difference did not meet the MID threshold (6 points). At 3 years, more men in the control group than in the spacer group had experienced a MID decline in urinary quality of life (6‑point decline: 30% compared with 17%; p=0.04; OR 0.41, 95% CI 0.18 to 0.95) and even large declines at twice the MID (12‑point decline: 23% compared with 8%; p=0.02; OR 0.31, 95% CI 0.11 to 0.85).
4.6 In the prospective multicentre RCT of 222 patients, hydrogel absorption was confirmed at 12 months (on MRI scans) in all the patients in the spacer group, with 2% (3/148) of them having small water density remnant cysts in perirectal tissues. In the case series of 27 patients, 17% (4/23) of balloons deflated prematurely at 3‑month follow‑up. This was presumed to be secondary to previously implanted fiducial markers. At 6‑month follow‑up, the balloons had deflated and been absorbed in all except 2 patients. In the comparative case series of 78 patients, at 6‑month follow‑up, hydrogel spacers were completely absorbed in all patients. In the balloon group, empty balloon envelopes were visible in 28% patients but showed no volume effect, and surrounding tissue was unaltered with no signs of fibrosis or inflammation.
4.7 The specialist advisers listed key efficacy outcomes as reduction of radiation dose to the rectum during radiotherapy, reduction in rectal toxicity, and increase in space and distance between the prostate and rectum.
4.8 One commentary from a patient who had experience of this procedure was received, which was discussed by the committee.