Hydrogel spacer may reduce prostate radiotherapy-induced rectal complications

The placement of an absorbable perirectal hydrogel spacer (HS) led to prostate-rectum separation with less rectal irradiation, fewer rectal toxicities, and better bowel-related quality of life (QoL) in men undergoing radiotherapy (RT) for prostate cancer (PCa), a meta-analysis has shown.

The anterior rectal wall is highly susceptible to radiation-induced toxicity owing to its anatomical proximity to the prostate. [Korean J Urol 2015;56:637-643; Int J Radiat Oncol Biol Phys 2015;92:971-977] “Thus, the rectum is the dose-limiting structure with prostate RT. Greater rectal irradiation during RT increases the risk of … gastrointestinal complications,” said the researchers.

“[As such,] identification of strategies that safely lower rectal irradiation during prostate RT is warranted … [S]trategies that allow dose escalation while decreasing rectal irradiation may optimize local tumour control with fewer bothersome bowel symptoms … [Our findings suggest that] perirectal HS placement prior to prostate RT may be a prudent preventive strategy for reduction of RT-induced rectal complications,” they said.

Data from seven studies (n=1,011) were analysed. A total of 486 men received HS prior to RT* while the remaining 525 did not (control arm). [JAMA Network Open 2020;3:e208221]

Pooled analysis of six studies showed that those who had HS received 66 percent less rectal irradiation vs those who did not (3.5 percent vs 10.4 percent; p=0.001).

Despite the comparable rates of grade ≥2 rectal toxicities between the HS and the control arms in early follow-up** (4.5 percent vs 4.1 percent; risk ratio [RR], 0.82; p=0.38 [six studies]), late follow-up saw a 77-percent lower risk with the former vs the latter (1.5 percent vs 5.7 percent; RR, 0.23; p=0.05 [four studies]).

In two studies, changes in bowel-related QoL were comparable in early follow-up (mean difference, 0.2; p=0.92) but greater with HS in late follow-up (mean difference, 5.4; p<0.001).

The risk of long-term rectal toxicities is ‘acceptably low’ with RT owing to newer technologies, and prophylactic measures for further risk reduction may have clinically insignificant benefit. [Cochrane Database Syst Rev 2018;1:CD012529] “[However, our findings] counter this argument because a statistically greater bowel-related QoL was associated with receiving [HS], and the magnitude of the benefit exceeded the threshold for a clinically meaningful difference.”

Spotlight on the backside

Collectively, the findings imply that perirectal HS placement before RT for PCa may cut rectal irradiation and the concomitant toxicities that clinically manifest after longer-term follow-up, said the researchers. However, despite the promising findings tied to HS in late follow-up, the duration of each study cannot fully characterize the real magnitude of rectal toxicities post-RT, they pointed out.

The median follow-up duration in the included studies reporting late rectal toxicities was 3.3 years. Evidence shows that rectal toxicity rates increased for at least 5 years before it plateaued. [Lancet Oncol 2016;17:1047-1060; Lancet Oncol 2016;17:464-474] “Thus, the clinical benefit of [HS] may … be underestimated in this review owing to limited duration of follow-up. Unfortunately, the number of studies providing results was insufficient to explore the association between follow-up duration and late grade ≥2 rectal toxic effects,” they said.

Despite several*** limitations, the findings provide a more reliable estimate of the effect size of the association between HS and clinical outcomes than would be obtained in a single study, noted the researchers. “Furthermore, the inclusion of the results obtained from clinical trials, as well as from commercial use, improves generalizability of the findings.”