"The take-home message is that Optilume is safe, and that it's superior to standard DVIU or dilation for the treatment of recurrent anterior urethral strictures that are less than 3 cm in length," says Sean P. Elliott, MD, MS, FACS.
Direct visual internal urethrotomy (DVIU) and urethral dilation are commonly used to treat urethral strictures in urologic patients, although their success rates are relatively low, compared to the more invasive urethroplasty.
In a recent study presented at the 2021 American Urological Association annual meeting,1 Sean P. Elliott, MD, MS, FACS, and his team of researchers conducted a randomized, single-blind trial that implemented the Optilume Drug Coated Balloon (DCB), a new treatment method that, when added to DVIU and urethral dilation procedures, is designed to improve the results of those treatments. Elliott is a professor, vice chair of urology, and director of reconstructive urology at the University of Minnesota.
Urethral strictures occur at a rate of about a 1/2 percent in the male population and account for hundreds of millions of dollars in health care expenditures every year. The gold standard for managing urethral strictures is urethroplasty, but that can be an invasive procedure with some adverse events even though it has excellent success rates. For a variety of reasons, nearly all patients end up getting their strictures treated with endoscopic therapy, meaning a direct vision internal urethrotomy, or DVIU, or urethral dilation. Success rates with these procedures are much lower than with urethroplasty; we’re talking less than 50%, especially for recurrent strictures, which was the focus of this study. So, this study aimed to see if an adjuvant therapy added to urethral dilation could improve that success rate, not as a replacement for urethroplasty, but as a bridge between plain old urethral dilation on 1 end of the spectrum and urethroplasty on the other end of the spectrum. Is there something we can offer those patients that's in between these extremes?
The Optilume drug coated balloon is a balloon that comes in a few different lengths and a couple of different widths. In this study, most of the balloons were 3 cm long and 30 Fr. It's coated with paclitaxel, which is commonly known to us as a chemo drug. Urologists are familiar with mitomycin C, which is another chemo drug that we've used to inject into strictures to keep them from coming back. Paclitaxel is just an alternative. It is also hydrophobic, so in order to help it dissolve into the tissues, it has a hydrophilic proprietary carrier molecule that helps it dissolve. The idea behind developing this was that some good results had been seen with mitomycin in the past, but there were also some complications as well. The theory was that if we could deliver the drug in a circumferential dose-standardized fashion, instead of injecting it in high doses in a few different spots, we might get better effectiveness with fewer adverse events.
Our primary outcome was anatomic success rate at 6 months. In the urethral stricture world, we talk about anatomic success and functional success. Anatomic success means, when you look in with a cystoscope or do an X-ray of the urethra, does the stricture appear to be open? Functional success would be things like questionnaires or flow rate—is the patient satisfied? Our primary outcome was anatomic success measured by cystoscopy and it was 75% in the drug coated balloon group vs 27% in the control group at 6 months. That alone was surprising to me. I did expect the Optilume group to do better, but not this much better than the control group. The control group did perform about as well as you would expect for a group that has had multiple previous dilations. The mean number of previous dilations in this group is 1.7, so you would expect them to have a success rate of around 30% and that's where they fell out—at about 30%. What was really surprising was that the Optilume was so good in this group. I was expecting something closer to 50%. Another finding was that we also measured freedom from repeat intervention through 1 year using a Kaplan Meier curve. And again, this was much better for the Opitlume group at 83% vs 21% for the control group. Flow rate and symptom scores measured by the International Prostate Symptom Score (IPSS) were also better in the intervention arm.
The take-home message is that Optilume is safe, and that it's superior to standard DVIU or dilation for the treatment of recurrent anterior urethral strictures that are less than 3 cm in length, which were the inclusion criteria for this study. And then I'd say that because of this, you can think of the Optilume drug coated balloon as an important alternative for men that have had an unsuccessful DVIU or dilation but want to avoid or maybe delay urethroplasty.
This shouldn't detract from the excellent results, but I would point out that only a couple of the patients had had radiation, so we can't really say whether this can be used for radiation strictures with good outcomes yet. Also, over 90% of the patients had bulbar strictures, so we don't have enough information yet to comment on how it works in penile strictures. Additionally, we don't have any information yet on how it works for what we would call posterior strictures, or bladder neck contractures. This was mostly bulbar strictures. And then I would say that people commonly wonder in a randomized trial, how were patients and surgeons blinded, and how does this impact on the interpretation of the results? I'll point out that all the patients were blinded out through 6 months, then it was revealed to them which device they had received. None of the surgeons could be blinded because they had to deliver the therapy, so you could think that because the surgeons weren't blinded, there could have been some bias in how they interpreted some of the outcomes. But, if you consider the fact that some outcomes that have absolutely no surgeon input, like patient questionnaires and flow rate, these things were still superior in the Optilume group. In terms of the patients getting unblinded after 6 months, you can question whether that impacts how they answer some of the questionnaires or their desire to cross over to the active arm of the study. But again, things that they can't have an impact on, like their maximum flow rate, were still better with Optilume. The results before they got unblinded were also better in the Optilume group.
In terms of this particular study, we'll be carrying the patient follow-up out through 5 years and I suspect that we'll have future subset analyses to dig deeper into the results that I'm presenting here. We'll also be looking at this device for other applications. You might see studies on whether it works, for instance, in radical prostatectomy or vesicourethral anastomotic strictures in the future.
1. Elliott S, DeLong J, Coutinho K, et al. Interim results for the robust III trial evaluating the optilume drug coated balloon for anterior urethral strictures. Paper presented during the 2021 American Urological Association annual meeting. September 10-13; virtual. Abstract MP56-07