ROBUST III: Optilume Drug-Coated Balloon for Recurrent Anterior Urethral Stricture
ROBUST III was a multicenter, single-blind, randomized superiority trial of Optilume paclitaxel-coated balloon dilation versus standard endoscopic management (uncoated balloon dilation, urethral sounds or direct vision internal urethrotomy) in 127 men with recurrent anterior urethral strictures of 3 cm or less after at least two endoscopic treatments, with anatomical success at 6 months as the primary endpoint. Success was 74.6% (50/67) with the drug-coated balloon (DCB) and 26.8% (11/41) with standard management, a difference of 44.4 percentage points (95% CI 27.6–61.1).[1]
- Design and population
- Multicenter, single-blind, 2:1 randomized superiority trial. 127 men with recurrent anterior urethral strictures of 3 cm or less and at least 2 prior endoscopic treatments.
- Arms
- Optilume paclitaxel-coated balloon dilation after predilation versus standard endoscopic management (uncoated balloon, urethral sounds or DVIU)
- Report and follow-up
- 2021 · 1 year (primary endpoint at 6 months; control arm followed to 1 year only)
| Endpoint | Results | Effect | Finding |
|---|---|---|---|
| 6-month anatomical success (16 Fr flexible cystoscope or 14 Fr catheter passed atraumatically), complete-case counts; difference in percentage points (DCB minus control) from multiple imputation | 74.6% (50/67) vs 26.8% (11/41) | difference 44.4; CI 27.6–61.1; P <0.0001 | Met |
| Kaplan–Meier freedom from repeat dilation, DVIU or urethroplasty at 1 year | 83.2% vs 21.7% | P <0.0001 | Met |
| Mean Qmax at 1 year (mL/s); baseline 7.6 (n=78) DCB and 7.4 (n=47) control | 15.5 (n=65) vs 7.6 (n=41) | — | Descriptive |
| Mean IPSS at 1 year; baseline 22.0 (n=79) DCB and 22.8 (n=47) control | 9.0 (n=67) vs 19.9 (n=42) | — | Descriptive |
Harms: Primary safety composite through 3 months (urethral fistula, unresolved de novo stress incontinence or urethral rupture): 0/79 vs 0/48; Post-procedure hematuria: 11.4% vs 2.1%; Dysuria: 11.4% vs 2.1%
Design
Men were adults with an anterior stricture of 3 cm or less and 12 Fr or narrower on urethrography, at least two prior endoscopic treatments, an International Prostate Symptom Score (IPSS) of 11 or higher and a peak flow rate (Qmax) below 15 mL/s. Prior urethroplasty, hypospadias repair, lichen sclerosus and unresolved confounders (bladder neck contracture, neurogenic bladder, benign prostatic hyperplasia) excluded patients. Enrollment ran from October 2018 to December 2020 at 21 US sites and 1 Canadian site. Randomization was 2:1 before the index procedure, stratified by prior pelvic radiotherapy and by number of prior endoscopic treatments (fewer than 5 versus 5 or more), and patients were blinded through the 6-month primary endpoint.[1]
At baseline 92.1% of strictures were bulbar and the mean length was 1.7 cm. Participants had a mean of 3.6 prior treatments, and 23/127 (18.1%) had five or more. Penile strictures numbered 8/79 in the DCB group and 2/47 (with recorded location) in the control group, and prior pelvic radiation was recorded in 9/79 and 6/48.[1]
The primary endpoint was anatomical success: atraumatic passage of a 16 Fr flexible cystoscope or a 14 Fr catheter through the treated segment at 6 months, with repeat intervention before 6 months counted as failure. Missing data were handled by multiple imputation, and a sample of 126 gave 90% power for a 32% between-group difference. The primary safety endpoint was freedom from urethral fistula, unresolved de novo stress incontinence or urethral rupture through 3 months. Freedom from repeat dilation, DVIU or urethroplasty at 1 year was a key secondary endpoint.[1]
Results
At 6 months, 50/67 DCB patients (74.6%) and 11/41 control patients (26.8%) with an evaluable result passed the lumen test; the model-based difference was 44.4 percentage points (95% CI 27.6–61.1; P < 0.0001), which met the primary endpoint. Cystoscopy was missing for 12 DCB and 7 control patients, and 2 DCB and 18 control patients had repeat intervention before 6 months. Assuming all 7 missing controls succeeded and all 12 missing DCB patients failed, success was still 63% versus 38%. The effect was consistent in prespecified subgroups with 5 or more versus fewer than 5 prior treatments and with stricture length of 2 cm or more versus under 2 cm; etiology, penile location and prior radiation subgroups were too small to assess. Among the 70 DCB patients and 11 control patients dilated with a 30 Fr balloon, success was 75% versus 22% (P < 0.01).[1]
Kaplan–Meier freedom from repeat intervention at 1 year was 83.2% with the DCB and 21.7% with standard management (P < 0.0001). Mean Qmax at 1 year was 15.5 mL/s versus 7.6 mL/s (baseline 7.6 and 7.4), and mean IPSS was 9.0 versus 19.9 (baseline 22.0 and 22.8); the report gives these as group means without a between-group test. In controls, Qmax rose through 30 days and then declined from 3 months, while IPSS fell through 30 days and then rose as symptoms worsened.[1]
The control arm was followed for 1 year and the DCB arm is followed annually to 5 years. In the DCB arm, Kaplan–Meier freedom from repeat intervention was 77.8% at 2 years (control arm at 1 year, 23.6%; difference 54.2 points, 95% CI 38.7–69.7) and 71.9% at 3 years.[2][3] Mean IPSS rose from 9.0 at 1 year to 10.1 at 2 years and 11.6 at 3 years, and Qmax fell from 15.5 to 12.6 and 10.6 mL/s. An IPSS improvement of at least 30% without repeat intervention was present in 61% (38/62) at 2 years and 48% (27/56) at 3 years, and treatment failures numbered 15 by 2 years and 20 by 3 years.[2][3] In an exploratory 2-year subgroup comparison, freedom from reintervention was 46.9% (95% CI 10.3–83.4) for penile strictures (n = 8) and 82.0% (95% CI 72.7–91.2) for bulbar strictures (n = 71).[2] Of the 48 control patients, 32 had recurrence and crossed over to the DCB; more than 75% of them were free from repeat intervention 1 year after crossover.[3]
ROBUST I, a separate single-arm cohort of 53 men with recurrent bulbar strictures of 2.0 cm or less treated at 4 Latin American sites, reached 5-year closeout with Kaplan–Meier freedom from repeat intervention of 71.7% and functional success (IPSS improvement of at least 50% without re-treatment) in 58% (25/43); 31 of 53 completed all follow-up. Functional success was 38% (8/21) with the 24 Fr balloon and 77% (17/22) with the 30 Fr balloon, a nonrandomized comparison.[4]
Surgery and treatment delivery
DCB-arm strictures were pretreated to at least 20 Fr with an uncoated balloon (92.4%), DVIU (5.1%) or both (2.5%); direct dilation with the DCB was avoided so that a stricture that dilated poorly would not receive a second paclitaxel dose. Balloon diameter and length were chosen from the lumen and the urethrographic stricture length to overlap normal urethra by 0.5–1 cm at each end. The most used diameter was 30 Fr, in 30 mm (28.2%) or 50 mm (60.8%) lengths. The balloon was inflated to its rated burst pressure for at least 5 minutes (mean 8 minutes 42 seconds from insertion to removal), then a 12–14 Fr Foley catheter was placed. Estimated post-treatment lumen on urethrography averaged 24 Fr in both groups.[1]
Control patients received the endoscopic method standard at their site: uncoated balloon dilation in 58.3% (24 Fr in 16, 28 Fr in 1, 30 Fr in 11), DVIU in 25.0% and urethral sounds in 16.7%, with no prespecified lumen goal.[1] Control patients with confirmed recurrence (recurrent symptoms, reduced flow and a lumen under 12 Fr on urethrography) could cross to the DCB before 12 months.[1] In the 2-year report the DCB cohort used 30 Fr in 70, 24 Fr in 6 and 36 Fr in 3 of 79 men.[2]
Adverse events
No participant had a primary safety event through 3 months. Adverse event types and rates were similar between groups except for post-procedure hematuria and dysuria, each 11.4% with the DCB and 2.1% with standard management; the events were mild and resolved within 30 days in 10 of 11 men. Serious adverse events occurred in 10.1% of DCB and 16.7% of control patients, and one serious urinary tract infection in each group was judged possibly related to the device or procedure. IIEF did not change in either group.[1]
In a nonrandomized cohort of 15 men, paclitaxel was detected in semen in 9/15 (60%) at 30 days, 5/13 (39%) at 3 months and 1/12 (8.3%) at 6 months; the authors recommend contraception through 6 months when the partner can conceive.[1] In the DCB arm, treatment-related hematuria was 13.9%, dysuria 6.3% and urinary tract infection 6.3% at 2 years, with no additional treatment-related events after 12 months.[2] At 3 years the figures were 11.4%, 7.6% and 6.3%, with no late treatment-related events.[3] Through 5 years ROBUST I recorded no serious treatment-related adverse events in 53 men, and 15 device- or procedure-related events, all grade 1–2.[4]
Limitations
Surgeons were not blinded, and patients were unblinded after 6 months, which could influence IPSS and the decision to undergo repeat treatment, particularly through crossover; Qmax and postvoid residual favored the DCB both before and after unblinding. The DCB arm received two dilations (pretreatment and coated balloon) against one in the control arm, and most controls were dilated with a 24 Fr balloon against 30 Fr in most DCB patients; post-treatment urethrograms showed similar lumen estimates, and the 30 Fr subset analysis agreed with the overall result.[1][2]
The primary outcome was missing for 12 DCB and 7 control patients. Penile strictures, prior pelvic radiation and lichen sclerosus were too few or excluded for any conclusion, and the effect of prior DCB treatment on later urethroplasty is unknown. The control arm was not followed beyond 1 year, so the 2- and 3-year DCB estimates have no concurrent control; IPSS data were available for 62/79 at 2 years and 56/79 at 3 years.[1][2][3] Urotronic was the sole funder of the 1- and 3-year reports, and several authors disclose consulting for the manufacturer.[1][2][3]
In conversation
- Parallel to OPEN (2020). The AUA panel read both randomized endoscopic-management trials together; OPEN used a symptom outcome and compared urethroplasty with urethrotomy.
- Parallel to OPEN (2020). Both trials used endoscopic treatment as the comparator in recurrent strictures; ROBUST III tested a paclitaxel-coated balloon, OPEN tested urethroplasty.
- Parallel to PINNACLE (2023). Same paclitaxel-coated balloon platform, tested in recurrent anterior urethral stricture rather than in BPH.
The AUA panel read ROBUST III together with the OPEN trial. OPEN used patient-reported voiding symptoms as its primary outcome in a comparison of urethrotomy with urethroplasty; ROBUST III used urethral patency at 6 months and freedom from retreatment at 1 year. The panel considered both trials at greater risk of bias as unreplicated single studies and described ROBUST III as an efficacy-style design in a highly selected population. ROBUST III did not compare the DCB with urethroplasty.[5]
Guidelines and approvals
- AUA, Urethral Stricture Disease guideline (published 2016, amended 2023). Statement 11b: surgeons may offer urethral dilation or direct visual internal urethrotomy, combined with drug-coated balloons, for recurrent bulbar urethral strictures <3 cm in length . The panel restricted the recommendation to recurrent bulbar strictures because penile strictures were about 10% of ROBUST III and the trial was not powered for them, and it states that the efficacy of repeated DCB use has not been ascertained and is not recommended.[5]
- EAU, Urethral Strictures limited update (2026). Offer drug (paclitaxel)-coated balloon dilatation for a short (<3 cm) bulbar stricture recurring after at least two prior endoscopic treatments, in patients not fit or unwilling to undergo urethroplasty . The summary of evidence is level 1b; the guideline reports ROBUST III as the randomized source and advises collecting data in a trial or registry for strictures outside the ROBUST indications.[6]
- FDA (December 3, 2021). Premarket approval P210020 for the Optilume Urethral Drug Coated Balloon to treat obstructive urinary symptoms associated with anterior urethral stricture in adult males with strictures of 3 cm or less. The summary of safety and effectiveness lists hypersensitivity to paclitaxel or structurally related compounds and urologic implants such as penile implants or artificial urinary sphincters as contraindications.[7]
Report history
| Published | Report | Cutoff | Headline results | Citation |
|---|---|---|---|---|
| 2021-12-02 | 1-year randomized report · primary | — | 6-month anatomical success (16 Fr flexible cystoscope or 14 Fr catheter passed atraumatically), complete-case counts; difference in percentage points (DCB minus control) from multiple imputation: 74.6% (50/67) vs 26.8% (11/41); difference 44.4; CI 27.6–61.1; P <0.0001 Met 6-month anatomical success if all 12 missing DCB patients failed and all 7 missing control patients succeeded: 63% vs 38%; — 6-month anatomical success, subset treated with a 30 Fr balloon (70 DCB, 11 control): 75% vs 22%; P <0.01 Kaplan–Meier freedom from repeat dilation, DVIU or urethroplasty at 1 year: 83.2% vs 21.7%; P <0.0001 Met Mean Qmax at 1 year (mL/s); baseline 7.6 (n=78) DCB and 7.4 (n=47) control: 15.5 (n=65) vs 7.6 (n=41); — Descriptive Mean IPSS at 1 year; baseline 22.0 (n=79) DCB and 22.8 (n=47) control: 9.0 (n=67) vs 19.9 (n=42); — Descriptive | Elliott SP, Coutinho K, Robertson KJ, et al. "One-Year Results for the ROBUST III Randomized Controlled Trial Evaluating the Optilume® Drug-Coated Balloon for Anterior Urethral Strictures." *J Urol.* 2022;207(4):866-875. doi:10.1097/JU.0000000000002346 DOI |
| 2023-12-18 | 2-year report (DCB arm) · updated | — | Kaplan–Meier freedom from repeat intervention, DCB arm at 2 years versus control arm at 1 year; difference in percentage points: 77.8% vs 23.6%; difference 54.2; CI 38.7–69.7; P <0.0001 Met Mean IPSS at 2 years in the DCB arm (baseline 22.0); paired t test versus baseline: 10.1 (n=62); P <0.001 Descriptive Mean Qmax at 2 years in the DCB arm (mL/s; baseline 7.6); paired t test versus baseline: 12.6 (n=58); P 0.003 Descriptive IPSS improvement of at least 30% without repeat intervention at 2 years: 61% (38/62); — Descriptive Kaplan–Meier freedom from reintervention at 2 years, penile strictures (n=8): 46.9% (95% CI 10.3–83.4); — Kaplan–Meier freedom from reintervention at 2 years, bulbar strictures (n=71): 82.0% (95% CI 72.7–91.2); — | VanDyke ME, Morey AF, Coutinho K, et al. "Optilume drug-coated balloon for anterior urethral stricture: 2-year results of the ROBUST III trial." *BJUI Compass.* 2024;5(3):366-373. doi:10.1002/bco2.312 DOI |
| 2024-08-30 | ROBUST I 5-year (single-arm cohort) · secondary | — | Functional success at 5 years (IPSS improvement of at least 50% without re-treatment): 58% (25/43); — Descriptive Kaplan–Meier freedom from repeat intervention at 5 years: 71.7%; — Descriptive Mean IPSS at 5 years, as observed (baseline 25.2, n=53): 7.2 (n=29); P <0.001 Descriptive Mean Qmax at 5 years, as observed (mL/s; baseline 5.0): 19.9; P <0.01 Descriptive Functional success at 5 years, 24 Fr balloon: 38% (8/21); — Descriptive Functional success at 5 years, 30 Fr balloon: 77% (17/22); — Descriptive | DeLong J, Virasoro R, Pichardo M, et al. "Long-Term Outcomes of Recurrent Bulbar Urethral Stricture Treatment With the Optilume Drug-Coated Balloon: Five-Year Results From the ROBUST I Study." *J Urol.* 2025;213(1):90-98. doi:10.1097/JU.0000000000004229 DOI |
| 2025-06-02 | 3-year report (DCB arm) · updated | — | Kaplan–Meier freedom from repeat intervention, DCB arm at 3 years versus control arm at 1 year: 71.9% vs 23.6%; — Met Mean IPSS at 3 years in the DCB arm (baseline 22.0): 11.6 (n=56); — Descriptive Mean Qmax at 3 years in the DCB arm (mL/s; baseline 7.6): 10.6 (n=53); — Descriptive IPSS improvement of at least 30% without repeat intervention at 3 years: 48% (27/56); — Descriptive Freedom from repeat intervention 1 year after crossover to the DCB (32 control patients with recurrence): >75%; — Descriptive | Srikanth P, DeLong J, Virasoro R, et al. "A Drug-Coated Balloon Treatment for Urethral Stricture Disease: Three-Year Results from the ROBUST III Study." *J Endourol.* 2025;39(9):968-974. doi:10.1089/end.2024.0718 DOI |
References
1. Elliott SP, Coutinho K, Robertson KJ, et al. "One-Year Results for the ROBUST III Randomized Controlled Trial Evaluating the Optilume® Drug-Coated Balloon for Anterior Urethral Strictures." J Urol. 2022;207(4):866-875. doi:10.1097/JU.0000000000002346
2. VanDyke ME, Morey AF, Coutinho K, et al. "Optilume drug-coated balloon for anterior urethral stricture: 2-year results of the ROBUST III trial." BJUI Compass. 2024;5(3):366-373. doi:10.1002/bco2.312
3. Srikanth P, DeLong J, Virasoro R, et al. "A Drug-Coated Balloon Treatment for Urethral Stricture Disease: Three-Year Results from the ROBUST III Study." J Endourol. 2025;39(9):968-974. doi:10.1089/end.2024.0718
4. DeLong J, Virasoro R, Pichardo M, et al. "Long-Term Outcomes of Recurrent Bulbar Urethral Stricture Treatment With the Optilume Drug-Coated Balloon: Five-Year Results From the ROBUST I Study." J Urol. 2025;213(1):90-98. doi:10.1097/JU.0000000000004229
5. Wessells H, Angermeier KW, Elliott SP, et al. Urethral Stricture Disease: AUA Guideline. American Urological Association; published 2016, amended 2023 (amendment: Wessells H, Morey A, Souter L, et al. J Urol. 2023;210(1):64-71. doi:10.1097/JU.0000000000003482). Statement 11b and discussion.
6. Lumen N, Campos-Juanatey F, Dimitropoulos K, et al. EAU Guidelines on Urethral Strictures. Limited update 2026. Arnhem: EAU Guidelines Office; 2026. Section 6.2.3.d.
7. U.S. Food and Drug Administration. "Summary of Safety and Effectiveness Data: Optilume Urethral Drug Coated Balloon (P210020)." December 3, 2021. accessdata.fda.gov