1

Introduction

Drug-coated balloon (DCB) dilation is an increasingly common treatment for male patients with urethral stricture disease (USD), with promising long-term results. ^, However, the utility of DCB dilation for female USD remains unknown. Here, we present a case wherein we performed Optilume® (North Plymouth, USA) DCB dilation on a female patient with short, distal USD.

2

Case presentation

A 64-year-old postmenopausal woman was referred to our tertiary reconstructive urology clinic with recurrent urinary tract infections and voiding lower urinary tract symptoms (LUTS). Her past medical history was significant for cervical dysplasia on colposcopy surveillance, breast cancer with remote right mastectomy (in remission) and three prior vaginal deliveries. She was previously assessed by a urogynecologist, who was unable to perform cystoscopy due to resistance in the distal urethra, with subsequent failed attempts at dilation past 14 French (F).

On our assessment, the patient described one to two years of increasing hesitancy and straining to void, along with a slow stream and sensation of incomplete emptying. She was experiencing intermittent dysuria with recurrent E.coli-positive urine cultures. There was no history of urinary incontinence or hematuria. Her kidney function was normal. Notably, the patient reported temporary improvement of her symptoms post-urethral dilation by an outside urologist. Given this, we arranged a cystoscopy to further investigate for potential USD.

A 17F flexible cystoscope was inserted per urethra and immediately, an approximately 12F distal urethral stricture was noted. The patient was dilated using female sounds from 12F to 20F, with the urologist remarking that the stricture felt “soft” during this process. The remainder of the cystoscopy was carried out, noting a healthy-appearing bladder mucosa with some debris. Pelvic examination demonstrated a grade 2 cystocele.

Two months later, the patient was seen in clinic for reassessment. She reported one month of significant improvement in her voiding LUTS; however, after this time point, her symptoms returned to baseline. She was scheduled for repeat cystoscopy which demonstrated a 12F recurrent, soft-appearing, distal urethral stricture. Voiding cystourethrogram (VCUG) was performed, albeit suboptimal for clear anatomic delineation ( Fig. 1 ). At the time, she voided 150ml with a peak flow of 8 ml/sec. Her post-void residual (PVR) was 0 ml.

Voiding cystourethrogram of female patient with urethral stricture disease.

Given the patient’s bothersome symptoms and evidence of recurrent stricture despite two prior dilations, a joint discussion was had regarding next steps in management. She was offered surveillance, repeat dilation under local anesthetic, direct visual internal urethrotomy (DVIU) ± DCB dilation under general anesthesia, and urethroplasty. She preferred to pursue alternatives to her prior failed dilations; however, did not wish to proceed to formal reconstruction. With this in mind, she was consented for DVIU with Optilume® DCB dilation under general anesthesia. A thorough discussion regarding the off-label use of DCB for female USD, including research limitations, was had.

In the operating room, a 19F rigid urethrotome with a zero-degree lens and half-moon DVIU blade was inserted per urethra. A 12F distal urethral stricture was noted, which appeared soft. The blade was advanced, making two incisions at 12′o clock, allowing our scope to pass. The stricture was approximately 1cm in length. The remainder of the urethra was unremarkable. Pan-cystoscopy was remarkable only for mild bladder debris. The urethrotome was exchanged for a rigid cystoscope with a 30-degree lens, which was manoeuvred into the bladder. A straight rigid guidewire was fed through the scope into the bladder under direct vision. A 3cm Optilume® DCB was selected based on the stricture length to ensure coverage of the stricture plus 1cm proximal and distal, as is recommended for male USD. The DCB catheter was passed over the wire and positioned appropriately. Given the short length of the female urethra, the scope was out of the urethra at this point. From the meatus, we observed the balloon inflate with normal saline until a pressure of 10 mmHg. The inflated DCB was held in place for 5 min for the active drug substance, paclitaxel, to be released. The balloon was then slowly deflated and removed. A 16F 2-way council-tipped catheter was fed over the wire into the bladder and the balloon inflated with 10ml of sterile water. The urinary efflux was clear. The patient was discharged home the same day with catheter in situ and no immediate complications.

She was seen in follow-up two days later and her catheter was removed. She voided 135ml with a peak flow of 13ml/sec and appropriate flow time. Her PVR was 30ml. One month later, she reported no bothersome LUTS, no hematuria or infections. Uroflowmetry was unable to be captured, although a PVR was 54ml. At four months, she continued to deny any LUTS. Most recently, at six-months she reported doing well with good flow and no bothersome LUTS. During uroflowmetry, she voided 135ml with a peak flow of 5ml/sec and slightly prolonged flow time. However, her PVR was reassuring at 0ml and given her lack of symptoms, there was no indication for cystoscopy.

3

Discussion

DCB urethral dilation has proven to be a safe and effective treatment option for male patients with anterior USD. ^, Optilume® DCB holds the chemotherapeutic agent, paclitaxel, a taxane which blocks mitosis thereby promoting stability of the stricture during the cell healing process following dilation. The ROBUST III randomized clinical trial follows male patients with recurrent anterior USD ≤3cm in length and ≤12F in diameter treated with Optilume® DCB vs. traditional endoscopic treatment. ^, The most up-to-date analysis two years post randomization showed that patients treated with Optilume® continued to experience meaningful improvements in International Prostate Symptom Score, peak flow rate and PVR. Furthermore, the freedom-from repeat intervention rate at two years was approximately 78 % in the Optilume® group-significantly greater than the control group at one year (24 %, p < 0.001). These results, while promising, do not include female patients, leaving much to be investigated regarding the utility of DCBs in women with USD.

We hypothesized that Optilume® DCB dilation would be feasible in our previously described female patient with a 12F distal, soft urethral stricture desiring management beyond straightforward dilation. Comparing our patient to the ROBUST III inclusion criteria, she had a distal, short (≤3cm) urethral stricture, which had failed two prior endoscopic treatments (average number of prior endoscopic interventions in ROBUST III was 3.2). This similarity in disease presentation was promising. To optimize results, we mimicked procedural steps from ROBUST III, ensuring we overlapped the stricture with 1cm of normal tissue on each end, allowing the paclitaxel to be released over 5min, and inserting a Foley catheter afterwards.

Female USD is rare in the general population yet discovered in approximately 7–20 % of women with bladder outlet obstruction. Although urethral dilation for female USD is a common practice, existing studies show it has relatively poor long-term efficacy. As a result, the American Urological Association stricture guidelines recommend offering urethroplasty to female USD patients. However, some patients, as in the case we present, may be reluctant to undergo formal reconstruction. The use of DCBs for female USD has been sparsely reported in the literature, with only one documented case report of its’ utility. Stuehmeier et al. described a 50-year-old woman with a history of urethral diverticulectomy and vaginal hysterectomy with a subsequent “1.8cm tight, fibrotic stricture involving the sphincteric urethra.“ They performed off-label Optilume® DCB dilation with a 3cm-sized balloon without complication. Notably, in this case, the pressure was maintained in the balloon for 10minutes (compared to 5min in our case and ROBUST III). At six months follow up, the patient had a peak flow of 26ml/sec with a low PVR. Further, a 16F catheter was able to pass easily.

4

Conclusion

This case report can be cited as the second-only published record of DCB dilation for female USD. Our patient demonstrated reasonable outcomes at six months; however, the sustainability of this effect remains unknown. We replicated the technique set forth by ROBUST III; however, further large-scale data is required to better understand optimal strategies for the procedure in women. As clinical trials yield durable results for male USD, other populations may seek to benefit from this novel biotechnology. Multi-center, international collaboration is encouraged to explore DCB dilation for female USD.

CRediT authorship contribution statement

Hannah S. Thomas: Conceptualization, Data curation, Formal analysis, Methodology, Writing – original draft. Noah Stern: Conceptualization, Data curation, Writing – review & editing. Sarah Neu: Conceptualization, Data curation, Supervision, Writing – review & editing. Sender Herschorn: Conceptualization, Data curation, Supervision, Writing – review & editing.

Consent

Patient data was anonymized, and consent obtained for research publication.

Funding

None.