Insights on Perirectal Spacing in Prostate Cancer

In the prostate cancer space, the use of perirectal spacers to reduce radiation toxicity has been an area of ongoing research, resulting in evolving practice standards. In this Urology Medical Perspectives series titled “The Role of Perirectal Spacers in the Treatment of Prostate Cancer,” Juan Montoya, MD, a urologist from The Urology Center of Colorado, offers clinical insights on the use of perirectal spacers and the emergence of polyethylene glycol–based hydrogel spacers in prostate cancer.

Urology Times®: How many radiotherapy procedures do you typically perform in your practice?

Juan Montoya, MD: Our practice, with somewhere in the order of 17 or 18 urologists, treats approximately 500 to 600 patients with prostate cancer a year. Of those, about 250 end up getting radiotherapy for prostate cancer.

Urology Times: What is the aim of perirectal spacing in patients with prostate cancer?

Juan Montoya, MD: Perirectal spacing increases the distance between the prostate, which is the target organ for radiation, and the rectum. By increasing that space, you reduce the dose of radiation to unintended structures, the rectum, which lowers the adverse effect profile. Increasing the distance between the target and the non-target organs is important with perirectal spacing.

Urology Times: What types of biomaterials are utilized in perirectal spacing for prostate cancer?

Juan Montoya, MD: This idea of creating a space between a target organ and non-target organs or nearby structures has been around in various ways for half a century. In the case of oral cancers, with the tongue, abdominal cancers, or even uterine cancer, this concept has been in active clinical investigation for many years. Over the past 2 to 3 decades, it has been looked at for prostate cancer. A number of substances have been tried to increase that space: hyaluronic acid, collagen, polyethylene glycol [PEG], and there was even an attempt at an inflatable silicone balloon with saline to temporarily create that space. Many things have been tried, and ultimately, polyethylene glycol has been used most consistently in recent clinical practice.

Urology Times: How do you optimize perirectal spacer placement? How does the use of hydrodissection facilitate placement?

Juan Montoya, MD: Perirectal spacing is a percutaneous transperineal procedure where a needle is placed under ultrasound guidance in the space between the scrotum and the anus. That needle is advanced to our target location, which is the tissue that separates the prostate and the rectum. Maximizing ultrasound to your benefit so that you get as good a visualization as possible in terms of the injection is critically important to the success of the procedure. Part of that is saline hydrodissection. Prior to the injection of the hydrogel, saline is injected into the space. It's called hydrodissection. It’s not so much creating the space as it is confirming that the space being created is correct and that we're getting a good symmetric distribution prior to the injection of the hydrogel. That allows us to make sure that we're getting optimal placement of the hydrogel.

Urology Times: Besides hydrodissection, are there any other tools that you use to confirm proper opening?

Juan Montoya, MD: The ultrasound becomes the critical piece to allow this to be done safely and successfully. I call it a Goldilocks approach. Trying to put that ultrasound probe relative to the patient, parallel to the patient, and with good depth and a good height are really important because you want to get that probe and that ultrasound maximized so you're getting the best visualization, which allows this procedure to be done safely. For example, you want the height of the probe to be just the right height so that you're not overly compressing that space and making the injection harder, but at the same time allowing enough contact between the probe, the rectum, and the prostate that you're getting good visualization. Those are the keys to important and successful placement of the hydrogel.

Urology Times: If you have a patient who has scar tissue in the perirectal space, how does that impact your procedure?

Juan Montoya, MD: Scar tissue in the perirectal space can clearly complicate and sometimes make it impossible to create an adequate space. In the case of patients who have inflammatory diseases or perhaps have had other treatments, that can cause scarring in the space where we're trying to incorporate the hydrogel. If it's sufficiently scarred, the hydrodisssection will not open any space, will not show that there's any space to create, and it may preclude successful injection. Most of the time, in many of these cases, it's still possible to get an adequate hydrodissection injected.

In fact, there's an abstract that was submitted for the last AUA [American Urological Association Annual Meeting] that looked at this in salvage radiotherapy. Individuals who had undergone a prostatectomy were injected with the hydrogel, and in 90% of those patients, it was possible to successfully create the space and insert the hydrogel. While scarring and prior procedures can be limiting, it doesn't necessarily preclude it, and the safe and adequate hydrodissection can confirm that's possible.

Urology Times: Can you talk about the results of the phase 3 pivotal trial that evaluated the PEG-based hydrogel spacer in patients receiving radiation therapy?

Juan Montoya, MD: The final results of the pivotal trial that led to the FDA approval of this polyethylene glycol hydrogel spacer were published in 2017. They found that there was a statistically significant reduction in grade 1 and grade 2 and higher rectal toxicity. There was also statistically significant improvement in bowel quality of life. There was a significant improvement in grade 1 urinary incontinence, although that appears to be clinically less important. At 3 years and the final analysis of that trial, they demonstrated that the grade 1 rectal toxicity was 9% in the control group and 2% in the treatment arm, and grade 2 rectal toxicity was nonexistent in the control arm and 4% in the treatment arm, so there's significantly reduced rectal toxicity and improved quality of life enhancement in the clinical trial that we demonstrated at 3 years.

Urology Times: Do you see similar results in your practice?

Juan Montoya, MD: In our practice, we continue to see those results as indicated in the pivotal trial, where there is improvement in rectal toxicity at 18 months and 3 years. Clearly, these patients benefit from the rectal spacing procedure, and that's reflected in our practice, as it was demonstrated in the clinical trial.

Urology Times: Let's briefly touch on the next-generation PEG-based hydrogel spacer. How has that changed your clinical practice? How does it compare with the first-generation product?

Juan Montoya, MD: This second-generation product is the standard polyethylene glycol hydrogel with iodinated contrast. It really allows visualization of the spacer with conventional imaging, the CT scan, so it allows for improved targeting, improved workflows in the radiation department, and it may reduce the need for another MRI in terms of planning. It's less on the urologist side but more on the radiation oncology side where we're seeing improvements in targeting and workflow that are important in efficiency and maximizing the care of these patients.

Urology Times: Are there any gaps in clinical trial evidence on PEG-based hydrogel spacers that require further research?

Juan Montoya, MD: Yes. The gaps in the research here are the difficulties of looking at things in a contemporaneous fashion. That is to say that, now in clinical practice, we're seeing more use of hypofractionation of patients with prostate cancer. In these patients, we're seeing fewer fractions, even some cases of extreme hypofractionation, and that probably translates to a higher GI [gastrointestinal] and rectal toxicity profile. At the same time as you're seeing this hydrogel being adopted and used, you're also seeing potentially increased risks based on the way that it's treated. In addition, the technology is advancing at the same time, so the ability to target the organ, the prostate, and limit the adverse effect profile is improving every day. Measuring this relative to the benefits and the risks of the treatment as clinical practice moves forward is difficult to do, but it would be important to try to look at that contemporaneously. Those are the gaps that hopefully time will fill.

Urology Times: Can you discuss the real-world data presented at AUA and the outcomes in patients who received the hydrogel spacer?

Juan Montoya, MD: In the clinical trials and the pivotal trial the led to the approval of the polyethylene glycol hydrogel spacer, the adverse effect profile looked to be very low. Patients did very well and there was very little reported significant rectal toxicity. Of course, that's an idealized clinical trial. Once something is adopted clinically and is being used by many different providers and practitioners with different abilities and different treatment algorithms, you start seeing real-world adverse effects and adverse events that were not identified in the initial clinical trials, and that's what we see here. It's probably the case that a clinical trial as an idealized version is not going to capture the full range of adverse effects and adverse event profiles, and when you look at real world, you'll start seeing adverse effects.

In particular, this abstract that was presented from an Australian group at AUA demonstrated that there's an adverse effect profile, including rectal wall injections, that were significant. Up to 41% of patients in that abstract were found to have rectal wall injections, sometimes leading to significant morbidity. I believe that ultimately, in clinical practice, 41% will greatly overestimate the risks of those adverse effects, but it's clearly going to be more than seen in the clinical trial. I think what you're going to find is that the risk of adverse events will be much smaller, and that's the opportunity for education, training, and improving the way this is done, enhancing the safety of the treatment.

Urology Times: What future advances are you looking forward to in the field? Do you have any advice or best practice recommendations for urologists who are also using perirectal spacers?

Juan Montoya, MD: Education and training is a piece that we can advance and improve on, and ensuring that this is done consistently and reproducibly. As ultrasound technology and visualization improves, that will also enhance our ability to do this in the safest fashion possible.

In terms of advice to give to providers and practitioners who are trying to adopt this in their practice, I go back to the ultrasound, and really maximizing your ability. This treatment is driven by your ability to visualize and to see well. And when that's the case, when you're getting adequate visualization, you're maximizing your opportunity to get a satisfactory injection, a good metric disbursement of the hydrogel, and good separation between the prostate and the rectum. I would always urge providers to ensure that the ultrasound is maximized. If they have to change or do anything in terms of their ultrasound probe positioning, that should be done. Because until the actual injection is performed, there's an opportunity to make this procedure better.