Originally published 11/8/2016
The use of an injectable hydrogel spacer to help minimize toxic effects of prostate cancer (PCa) radiation on the rectal wall has become a standard of care since we posted the 2016 blog below. By implanting the hydrogel into the tissue between the prostate and the rectum, a wider space is created, which “may significantly reduce the [radiation] dose received by the rectum and the risk of rectal toxicity [side effects, see explanation in the blog below].”[i] How well does it work?
A 2021 study of 32 patients with localized PCa who had the spacer applied before hypofractionated radiotherapy (HRT) suggests that it is effective in lowering side effects to bowel structures. 13 patients were low risk (Grade Group 1), 16 were favorable intermediate risk (GG 2) and 3 were unfavorable intermediate risk (GG 3). Prior to treatment, 22 men reported normal sexual function. After treatment, follow-up occurred every 3 months for 2 years, and going forward every 6 months. Relapse was defined as PSA nadir (lowest PSA) plus 2 ng/ml. Genitourinary (GU and gastrointestinal (GI) side effects were evaluated during follow-up, as was sexual function. Treatment was aimed at the whole gland plus seminal vesicles. The majority had Grade 0 toxicity as follows:
| Grade 0 late toxicity | ||
| Gl (bowel function) | 78.1% Grade 0 toxicity | No late toxicity (any grade) |
| GU (urinary function) | 28.1% Grade 0 toxicity | 93.7% Grade 0 toxicity |
In addition, 88.1% of patients who had pretreatment potency maintained it at 15 months. Although there were higher rates of overall acute and late-onset urinary side effects (most were mild), the authors demonstrated that the hydrogel spacer had reduced acute and late-onset rectal side effects.[ii]
One other 2021 study has a bearing on the subject. A study involving 160 patients demonstrated that an improved placement area for the hydrogel offers even greater protection for the rectal area. The patients were all treated with beam radiation, but were divided into three groups: 30 men received no spacer, 100 men received standard spacer implantation, and 30 men received a new placement technique. The authors found that the third group had the largest separation between prostate and rectal wall, while the first group had the smallest separation. In terms of radiation dose, the third group had the least radiation exposure to the rectum.[iii] Thus, the most recently published data supports the use of a hydrogel spacer to protect the rectum during beam radiation for PCa.
It’s a fact that all radical (whole gland) prostate cancer treatments come with some risk of side effects. For this reason, many patients struggle with what seems like a poor trade-off: cancer control at the possibility of reduced quality of life. It’s no wonder that a growing number of patients are turning to targeted treatments such as MRI-guided Focal Laser Ablation (FLA).
However, based on the location and extent of prostate cancer, not every patient will qualify for a focal approach. Furthermore, not every patient is a candidate for radical prostatectomy due to age or preexisting health conditions – and many men don’t wish to go through surgery. Therefore, about a third of newly diagnosed patients turn to some form of radiation treatment (beam or seed implants).
Radiation not only damages cancer cells, but it also affects nearby healthy cells. The prostate gland lies next to the rectal wall, so the scatter effect of radiation can injure the colon and/or the rectum – a very unpleasant risk, to say the least. These structures are the most vulnerable to radiation harm resulting from prostate cancer treatment. According to the International Foundation for Functional Gastrointestinal Disorders (IFFGD), despite the best efforts of doctors to avoid harm to the rectum and colon, “significant rectal injury remains a far too common side-effect.” [iv] This includes diarrhea, urgency, bowel incontinence, and rectal bleeding. When such problems occur during or very soon after a course of radiation, they are called acute adverse events. What most patients don’t realize is that such side effects may not show up for months or even as late as 2 years after treatment. These are called late-onset adverse effects. Another word for adverse effects is toxicities.
Gastrointestinal adverse events are ranked according to a 4-point grading scale:
- Grade 1 – Mild and self-limiting. Includes bleeding, mucous discharge, mild rectal discomfort, loose stools not requiring medication.
- Grade 2 – Can be managed conservatively, does not affect lifestyle. Includes intermittent rectal bleeding that does not require pad use, diarrhea requiring medications.
- Grade 3 – Severe side effects that alter lifestyle. Includes rectal bleeding that requires pad use and minor surgical intervention, rectal pain requiring narcotics, and ulcerations of the rectum.
- Grade 4 – Life threatening and disabling. Includes blockage of the bowel, a hole in the rectal wall (fistula), bleeding requiring hospitalization, and necessary surgical intervention
Most radiation-induced toxicities are Grade 1 or 2, and most do not last long. However, if late-onset toxicities are still there 3 years later, it is considered permanent.
Efforts to prevent radiation-induced toxicities have included varying dosage amounts and duration of radiation therapy. Radiation technologies have been developed to achieve better focus of the beam radiation and limit scatter, e.g. IMRT (Intensity Modulated Radiation Therapy), SBRT (Stereotactic Body Radiation Therapy), and proton beam. For each, there is still rectal exposure, even if less than with traditional external beam radiation. For example, a 2013 study reported what the authors called “exceptionally” high rates of late-onset Grade 2-3 adverse events following IMRT.[v]
Now there is a new approach to protecting the rectum: a hydrogel that is injected into the thin layer of tissue (fascia) between the prostate and rectum to act as a “spacer.” The hydrogel is composed of two liquids (the majority of it is water) that form a biocompatible get-like substance. Injecting the hydrogel is done under general or local anesthesia, and most patients tolerate the procedure well, though as many as 10% have reported rectal pain or discomfort. As the body gradually absorbs the hydrogel (up to 12 months) the space slowly returns to normal. There are few published studies that compare spacer vs. non-spacer (control) results. The results point to similar rates of acute (short-term) adverse rectal events, but those patients who had the hydrogel had fewer late-onset toxicities than the control patients, and the toxicities were less severe.
The latest study, presented at the September 2016 annual meeting of the American Society for Radiation Oncology (ASTRO), tracked 222 patients for a median of 37 months after radiation treatment using IMRT. About 2/3 of the patients received the spacer, while 1/3 acted as a control group (no spacer). As reported by Medscape, “With regard to rectal toxicity, the control group, when compared with the hydrogel group, had a higher incidence of both grade 1+ and grade 2+ events.”[vi] In other words, a smaller percentage of spacer patients had problems. According to a 2016 study of 30 patients, acute Grade 1 gastrointestinal toxicity rates were 43% for the spacer group vs. 50% for the control group; acute Grade 2 rates were 0% for the spacer group vs. 4.5% for the control group. Late-onset Grade 1 rates were 16.6% for the spacer group vs. 41.8% for the control group.[vii]
Prostate cancer patients considering radiation should be made aware that radiation does not immediately destroy the cancer. Instead, over time it interferes with the cancer cells’ ability to reproduce. For this reason, the treatment requires lengthy exposure – whether it is the number of treatment sessions or the implanting of permanent radioactive seeds – to keep the pressure on the cancer cells. For those who can’t have (or don’t want) prostatectomy, or who are not candidates for a focal treatment, radiation has proven to be very effective. Today’s radiation modalities that are more narrowly focused offer greater success with reduced side effect risks.
Our Center’s advanced 3T multiparametric MRI can help determine which type of treatment can benefit patients, specifically, for those who are considering radiation therapy for prostate cancer. Our diagnostic images and in-bore MRI-guided targeted biopsy produce the most accurate diagnosis. Submitting tumor cells for additional genomic analysis can also help determine the type and dosage of radiation.
Meanwhile, given the risk of bowel or colon problems following prostate cancer radiation, the hydrogel spacer seems like a constructive step toward reducing bowel side effects.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
References
[i] Pepe P, Tamburo M, Pennisi M, Marletta D, Marletta F. Clinical Outcomes of Hydrogel Spacer Injection Space OAR in Men Submitted to Hypofractionated Radiotherapy for Prostate Cancer. In Vivo. 2021 Nov-Dec;35(6):3385-3389.
[ii] Ibid.
[iii] Fukumitsu N, Mima M, Demizu Y, Suzuki T et al. Separation effect and development of implantation technique of hydrogel spacer for prostate cancers. Pract Radiat Oncol. 2021 Nov 18:S1879-8500(21)00300-3.
[iv] “Radiation Induced Injury to the Colon and Rectum.” https://www.iffgd.org/other-disorders/radiation-therapy-injury.html
[v] Nishimura T, Yamazaki H, Aibe N, Nakamura S et al. Exceptionally high incidence of grade 2-3 late rectal toxicity in patients with prostate cancer receiving hypofractionated (2.2 Gy) soft tissue-matched image-guided intensity-modulated radiotherapy. Anticancer Res. 2013 Dec;33(12):5507-10.
[vi] Mulcahy, Nick. “’Good Tool:’ Hydrogel Spares Rectum from Radiation.” Medscape Medical News, Sep.. 28, 2016. http://www.medscape.com/viewarticle/869398
[vii] Whalley D, Hruby G, Alfieri F, Eade T. SpaceOAR Hydrogel in Dose-escalated Prostate Cancer Radiotherapy: Rectal Dosimetry and Late Toxicity. Clin Onc. 2016 Oct;28(10):e148-e154.
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
