Traditional endoscopic stricture treatment does not offer good long-term results. Dilation and internal urethrotomy have similar success rates to each other.¹ In the optimal patient with a treatment-naïve 1-cm bulbar stricture, success rates at 2 years are about 50%. In any patient with a less than ideal stricture (>1 cm, nonbulbar location, repeat treatment, radiation) the long-term success rates are <20%.^2,3 Therapies that have been used to augment the success of dilation/urethrotomy include self-dilation and endourethral adjuvant medications. Self-dilation can stave off stricture recurrence, but strictures do not “stabilize” at the size of the catheter; as soon as self-dilation is stopped, the stricture recurs.^4,5 Further, self-dilation is associated with a poor quality of life, especially in younger men or men with a more proximal stricture.⁶ In a systematic review, hyaluronic acid and mitomycin C show the most promise for reducing stricture recurrence rates when used in conjunction with endoscopic treatment, although success rates are less encouraging with long-term follow-up.⁷ High doses of mitomycin C or use in radiated patients has been associated with adverse outcomes.⁸

Optilume is a paclitaxel-coated balloon that offers combined axial dilation with circumferential drug delivery in a standardized dose. The balloon is a low-pressure balloon (12 atmospheres), so it should be used as a drug delivery device. Stricture predilation should first be achieved with a high-pressure balloon (20 atmospheres) such as the UroMax balloon. Paclitaxel has been used previously in the prevention of atherosclerotic recurrence after angioplasty in the peripheral vasculature. Paclitaxel is hydrophobic, so it depends on a hydrophilic carrier molecule to help it dissolve into the spongiosum. The carrier molecule washes out with urination, leaving the paclitaxel in place. Animal studies have shown that fibrin deposition is most active in the first few weeks after urethral injury. Paclitaxel levels are highest in the tissue during these first few weeks (T_1/2 in urothelium 3-7 days) when it works to prevent scar formation, allowing time for urethral healing.

There have been 3 industry-funded studies of Optilume: Re-Establishing Flow Via Drug Coated Balloon For The Treatment Of Urethral Stricture Disease I, II, and III (or ROBUST I, II, and III). ROBUST I and II were phase 1/2, single-arm, open-label studies of safety and initial efficacy performed in Latin America (n=53) and the United States (n=16), respectively.^9,10 ROBUST III was a phase 3 randomized, single-blind, placebo-controlled trial in North America (n=127).¹¹ The overwhelming majority of these strictures were bulbar in location and the mean stricture length was 1-2 cm. The median number of prior dilations/urethrotomies was 2, 4, and 3 in ROBUST I, II, and III, respectively. The primary end point in all 3 studies was the ability to atraumatically pass a flexible cystoscope at 6 months. The primary long-term outcome was International Prostate Symptoms Score (IPSS). Follow-up is now complete through 4 years for ROBUST I, 3 years for ROBUST II, and 2 years for ROBUST III.

As we compare the outcomes across these studies, a few themes start to emerge. Firstly, at 6 months, cystoscopic success among men receiving active treatment (Optilume) is remarkably similar across the 3 studies (73%-75%). The control arm (uncoated balloon or urethrotomy) had a success rate of 27%, remarkably similar to what one would expect based on historical controls with 3 prior treatments of a short bulbar stricture.² Whether we compare the 75% 6-month cystoscopic success with Optilume to the controls in ROBUST III or to historical controls, the outcomes with Optilume are clearly superior by 2- to 3-fold.

Second, success rates, as measured by IPSS are consistent across studies and are durable over time. In ROBUST I, II, and III, IPSS scores among men receiving Optilume decrease from 22 pretreatment to 7 immediately posttreatment and remain <10 through 4 years. So, even though we only have 2 years of follow-up for the ROBUST III randomized trial, we might infer that their IPSS outcomes should stay stable through 4 years, like the ROBUST I men. IPSS in the control group was likewise 22 pretreatment and declined to <10 posttreatment but increased to 16 at 1 year.

Thirdly and lastly, Optilume has been shown to be very safe across all 3 studies. The adverse effects that are more common after Optilume, compared to control, are hematuria and dysuria. While it is impossible to know why this occurs, I suspect it is evidence that the drug is working—wound contracture is being delayed or prevented and the split in the urothelium is staying open longer, leading to more hematuria from open vessels and pain from the wound being exposed to urine flow. So I find these adverse effects to be expected and encouraging signs.

We don’t know yet how Optilume works in radiated strictures or in vesicourethral anastomotic stenosis. Hopefully we will see data on that soon. Further, there is early evidence that Optilume will be just the first of many technological innovations we will see in urethral stricture disease. Dr Nick Warner has pioneered endoscopic urethroplasty using an Endo Stitch device.¹² Perhaps his early success with this technique will lead to further investments by industry in minimally invasive treatments for urethral stricture.