Current endoscopic management of anterior urethral strictures includes mechanical dilation or direct visualization internal urethrotomy (DVIU), however long-term success rates are in the range of 35-70% for primary treatment. Multiple endoscopic treatments of the same stricture lead to progressively worse outcomes. The Optilume® Urethral Drug Coated Balloon (DCB) is a urethral dilation balloon with a proprietary paclitaxel coating that combines mechanical dilation of the stricture for immediate symptomatic relief with local drug delivery to maintain urethral patency. ROBUST III is a prospective, multicenter, randomized, controlled single-blind trial to evaluate the safety and efficacy of the Optilume DCB against standard of care endoscopic management of recurrent anterior urethral strictures.

Adult men with anterior strictures ≤12F and ≤3cm in length, at least 2 prior endoscopic treatments, International Prostate Symptom Score (IPSS) ≥11, and maximum flow rate (Qmax) <15 mL/sec were randomized 2:1 to receive treatment with the Optilume DCB or standard of care endoscopic management (Control). Subjects with previous urethroplasty or unresolved confounding etiologies (e.g., bladder neck contracture, BPH) were excluded. Subject follow-up post-procedure occurred at 2-5 days (Foley removal), 30 days, 3 months, 6 months, and 1 year. Subjects were blinded to treatment received through 6 months. 
The primary endpoint was the proportion of subjects that were stricture free at 6 months as measured by the ability to pass a 16Fr flexible cystoscope or 14Fr catheter through the treated area. Secondary endpoints included freedom from repeat treatment of the study stricture, IPSS, and Qmax. Sexual function was evaluated utilizing the International Index of Erectile Function (IIEF) questionnaire. Subjects who underwent repeat intervention on the study stricture were considered failures for categorical endpoints or assigned the worst observed value for continuous endpoints for timepoints after the intervention. The primary safety endpoint was freedom from a composite of serious device or procedure related complications, including formation of a rectal fistula, unresolved de novo stress urinary incontinence, and urethral rupture or burst. Paclitaxel concentration was measured over time in blood (plasma), urine, and semen in a pharmacokinetic (PK) sub-study.
The statistical hypothesis test for the primary endpoint was based on a two-sample continuity corrected Chi-square test at the two-sided 0.05 (one-sided 0.025) alpha level. A minimum of 126 subjects provided at least 90% power to show superiority of Optilume DCB to standard of care.

The study enrolled and randomized 127 subjects at 23 clinical sites in the United States and Canada (Optilume DCB=79, Control=48). Baseline characteristics were similar between groups, with subjects having an average of 3.6 prior endoscopic treatments and stricture length of 1.7 cm. The majority of strictures were located in the bulbar urethra (92.1%) and were idiopathic in origin (51.2%). Primary 6-month follow-up is complete and 1-year follow-up is ongoing. The proportion of subjects remaining stricture-free at 6 months was 74.6% (50/67) in the Optilume DCB group compared to 26.8% (11/41) in the Control group (p<0.001). Outcomes were consistent among subgroups with ≥5 vs <5 dilations and for lengths <2cm vs ≥2cm. The Kaplan Meier estimate for the rate of freedom from repeat intervention through 1-year follow-up was significantly higher for the Optilume DCB as compared to Control.  Immediate symptomatic improvement was seen in both groups, however the Control group exhibited symptom scores approaching baseline levels by one year while the improvement in the Optilume group was sustained. A similar trend was seen in Qmax. There was no significant change in IIEF scores in either group. No subjects experienced a serious device related complication. The most frequently reported adverse events included common post-procedural events such as urinary tract infection, post-procedural hematuria, and dysuria. Systemic exposure to paclitaxel was minimal, with a maximum plasma concentration of 0.12 ng/mL achieved immediately post-procedure. Paclitaxel concentration in urine and semen reduced to near the limit of quantitation by 30 days and 3 months post-procedure respectively.

This randomized controlled trial showed that a significantly higher proportion of subjects remained stricture free 6 months after treatment with the Optilume DCB compared to standard endoscopic management. At 1 year, freedom from repeat intervention was significantly higher in the Optilume DCB group. While both groups showed immediate improvements in symptom severity and voiding function, the benefits were more durable in the Optilume DCB group. Neither group showed a significant change in sexual function through 1 year. The Optilume DCB procedure was safe and well-tolerated. Although published data suggests that stricture recurrence typically occurs within 6-12 months after endoscopic treatment, longer follow-up is needed to capture patients with delayed recurrence.

The Optilume DCB exhibited a significant improvement in both objective and subjective outcomes through 1-year post treatment compared to standard of care and represents a potential breakthrough in the endoscopic management of recurrent anterior urethral strictures. Follow-up through 5 years is planned to further define the durability of the treatment.