Radiotherapy is an effective treatment for localised prostate cancer. Advances in radiotherapy techniques aim to increase the dose of radiation given to the prostate area, whilst reducing side effects from the treatment. One possible side effect from prostate radiotherapy is bowel problems. Promising new clinical trial data indicate that injection of a hydrogel spacer can reduce the bowel side effects caused by radiotherapy.
Radiotherapy treatment of localised prostate cancer
External beam radiotherapy (EBRT) uses a beam of radiation aimed at the prostate to kill the cancerous cells. Treatment usually extends over a few weeks. Men undergoing radiotherapy sometimes experience side effects such as bowel incontinence (loose stools), frequent or painful urination or blood in their urine or stools. These side effects are often temporary, disappearing soon after treatment ends. Unfortunately, some men suffer from side effects over a longer period of time.
During radiotherapy, the beam of radiation is aimed at the prostate from many different directions. This helps to concentrate the dose of radiation given to the prostate, whilst reducing the dose given to the surrounding parts of the body. As the bowel and bladder are close to the prostate, the radiation can affect these organs too. Advances in radiotherapy aim to give a higher dose of radiation to the prostate while reducing the toxic effects to the surrounding areas of the body. But the close proximity of the bowel and bladder to the prostate limits technical advances.
"Spacers" aim to reduce bowel toxicity during prostate radiotherapy
A new technique aims to increase the distance between the prostate and the rectum. A "spacer" material is injected into the space between the prostate and the rectum. This spacer expands, pushing the prostate and rectum apart. The aim of spacers is to reduce the radiation directed at the prostate that also reaches the rectum. A higher dose of radiation can therefore be used to treat the prostate, with less toxic effects on the rectum.
The first report of spacers to protect the rectum from radiation was published in 2006. Since then, a number of different spacer materials have been tested for their effectiveness. These include collagen, hyaluronic acid (a biological molecule similar to carbohydrates), absorbable balloons and a compound called polyethylene glycol (PEG) hydrogel. PEG hydrogel is the only spacer to have been tested in a large randomised controlled trial.
PEG hydrogel is a synthetic polymer - a water-soluble gel-like material with many uses. There are different types of PEG, with various uses in chemical and biological processes. The PEG hydrogel used as a spacer for men having radiotherapy is a non-toxic substance that is injected as a liquid, forming a solid gel about 10 seconds after injection. This hydrogel maintains its gel-like state for at least 3 months. It slowly breaks down over time, being absorbed into the blood stream and lost through the urine.
Clinical trial to test hydrogels
Use of the PEG hydrogel spacer has been tested in a randomised controlled trial in the US. 222 patients with localised prostate cancer were recruited to the trial at multiple treatment centres. Patients were divided into two groups. 149 men received the hydrogel injection and 73 did not. The patients received the injection under anaesthetic, so they didn't know which group they were in. After hydrogel injection, all participants had a course of image-guided Intensity Modulated Radiation Therapy (IMRT) to treat their prostate cancer.
The aim of the US trial was to ask whether the spacer reduced the radiation reaching the rectum and whether side effects were reduced during and after radiotherapy.
The spacer successfully reduced the amount of radiation reaching the rectum. 97.3% of the men with the spacer had a decrease in rectal radiation dose of 25% or more. The spacer also decreased radiation to the penile bulb (the start of the penis, closest to the body).
The trial kept track of all reported bowel side effects, such as bleeding, pain and loose stools. The participants were interviewed weekly during IMRT treatment, then at 3, 6, 12 and 15 months after hydrogel injections. Bowel problems at the early stages of treatment were very similar between the two groups of patients. Less of the patients who received the spacer felt rectal pain during IMRT treatments. After IMRT treatment was finished, there was a reduction in the proportion of men who experienced bowel symptoms. 2% of men with the spacer had bowel symptoms in the 12 months after treatment, compared to 7% of men who did not receive the spacer. By 12 months after treatment, 21.4% of patients reported a decline in the bowel-associated quality of life, compared to only 11.6% of men who received the hydrogel spacer.
The hydrogel spacer was injected safely, and most doctors considered it "easy" or "very easy" to use. The spacer added an average of 11mm of extra space between the rectum and the prostate. MRI scans showed that the spacer had been absorbed and could no longer be seen by 12 months after its insertion.
Australian trial of the hydrogel spacer
A recent publication from an Australian group examined the pros and cons of the hydrogel spacer for Australian men. While not a randomised controlled trial, this study reported on the experiences of Australian men using hydrogel spacers to reduce toxicity during radiotherapy. The first author is Dr Michael Chao, radiation oncologist at Genesis Cancer Care and The Austin Hospital in Victoria. The senior author of the study is A/Prof Nathan Lawrentschuk, working through The Austin Hospital.
The Australian study followed the experiences of 76 men with localised prostate cancer. They each had an injection of hydrogel spacer under general anaesthetic. This was followed by IMRT or another radiotherapy technique called volumetric-modulated arc radiation therapy. The men were followed-up for an average of 14 months after radiotherapy was finished.
The 76 Australian men receiving the hydrogel spacer did not have any complications arise as a result of hydrogel injection. None of the men reported rectal bleeding. There were some low-grade symptoms during treatment with radiotherapy. 21% of patients reported low-grade symptoms, with all resolved by 3 months, at the end of the radiotherapy. 3% of the patients developed symptoms after the radiotherapy, but all of these were low-grade.
The Australian study showed that a relatively low dose of radiation hit the rectum of the patients. This was apparent even in the men whose prostates were large. The study did not have a control group, like the US randomised trial. So the authors compared the experiences of these 76 patients with similar patients at the same hospital. This comparison isn't perfect, as the two groups of patients may have considerably different characteristics. But it does give an indication of how well the hydrogel is working. The men who had the spacer had a lower average dose of radiotherapy to the rectum than similar patients who did not have the spacer. The radiation doses and bowel symptoms described in the Australian study are quite similar to the previous clinical trial in the US.
The US clinical trial indicated that a hydrogel spacer can reduce the dose of radiation to the rectum during prostate radiotherapy. The recent Australian study has found that Australian men had similar experiences of benefit from the hydrogel spacer, with few drawbacks. This new technique will hopefully improve prostate radiotherapy in Australia.
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