Treatment of Urethral Stricture Disease in Women: a Multi-Institutional Collaborative Project

Lane G1, Anger J2, Brandes E3, Carmel M4, Chung D5, Cox L6, DeLong J7, Elliott C8, Eltahawy E9, França W10, Gousse A11, Hagedorn J12, High R13, Khan A14, Padmanabhan P15, Lee R16, Lucioni A17, MacDonald S18, Powell C19, Sajadi K20, Smith A21, Vollstedt A22, Welk B23, Cameron A1

Research Type

Clinical

Abstract Category

Urethra Male / Female

Best Clinical Abstract
Abstract 1
Best Urology
Scientific Podium Session 1
Thursday 19th November 2020
18:00 - 18:15
Live Room 1
Surgery Female Retrospective Study Outcomes Research Methods
1. University of Michigan, 2. Cedars-Sinai, 3. Dartmouth Hitchcock Medical Center, 4. University of Texas Southwestern Medical Center, 5. Columbia University, 6. Medical University of South Carolina, 7. Eastern Virgina Medical Center, 8. Santa Clara Valley Medical Center, 9. University of Arkansas for Medical Sciences, 10. Hospital do Servidor Público Estadual de São Paulo, 11. Memorial Hospital Miramar, 12. University of Washington, 13. Baylor Scott & White, 14. Mayo Clinic Arizona, 15. Kansas University Medical Center and Beaumont Hospital, 16. Weill Cornell Medicine, 17. Virginia Mason Medical Center, 18. Penn State Hershey Medical Center, 19. Indiana University, 20. Oregan Health & Science University, 21. University of Pennsylvania, 22. Beaumonth Hospital, 23. Western University
Presenter
Links

Abstract

Hypothesis / aims of study
Female urethral stricture disease is rare and little guidance exists on its surgical treatment. Several surgical approaches exist to treat female urethral stricture, including endoscopic dilations (ENDO), urethroplasty with local tissue (vaginal) flap (ULT) and urethroplasty with free graft (UFG). However, outcome data comparing these approaches is limited and large, multicenter studies comparing different techniques directly are non-existent. [1] This study aims to evaluate the outcomes of surgical treatment for female urethral stricture.
Study design, materials and methods
This is a multi-institutional retrospective cohort study of surgery for female urethral stricture disease. Women who underwent surgery for urethral stricture disease from 2010-18 were included. Women with malignancy, congenital disease, undergoing gender affirming and office based surgery were excluded. Authors from each institution directly submitted de-identified data into a central database (REDCap). 

The REDCap database included comprehensive information on patient demographics, medical history, urethral stricture history, presenting symptoms and patient reported outcome measures, preoperative diagnostic assessment, urethral stricture surgery, and post-operative follow-up at three visit times: initial postoperative visit (2-6 weeks), second postoperative visit (>6 weeks postoperatively), third postoperative visit (most recent visit). 

Surgeries were grouped into three categories endoscopic (ENDO), urethroplasty with local tissue flap (ULT) and urethroplasty with free graft (UFG).  For the primary outcome of interest, time from surgery to stricture recurrence by surgery type, a Kaplan-Meier time to event analysis was performed. To adjust for confounders, a Cox-proportional hazard model was fit for time to stricture recurrence. The Cox-proportional hazard model was adjusted for the covariates listed in the Table.
Results
Twenty-three surgical centers contributed data, the majority of which were from academic centers within the United States (90%). A total of 1051 patient charts were reviewed and after exclusions 248 patients charts were abstracted. Of these, 215 patients met inclusion criteria. Patients were mostly caucasian (73%) with a mean age of 56 years (SD 13). The majority of patients were post menopausal (70%).  The etiology of stricture formation was unknown or missing for 25% (N=55), idiopathic for 17% (n=37), prior instrumentation (cystoscopy or non-stricture urethral dilation) for 16% (n=34),  and catheter related for n=20 (9%). 

Types of surgery performed were evenly distributed (ENDO: 35% (n=75),  ULT: 33% (n=72), UFG: 32% (n=68)). The majority of ENDO surgeries were cystoscopy with dilation (90%). ULT surgeries primarily consisted of vaginal advancement flap (46%) or tubularized vaginal flap (40%). UFG were primarily dorsal onlay (94%) using buccal grafts (97%). There were no differences in demographics nor etiology of stricture between groups. 
 
Overall, 65% of women remained recurrence free (n=120/185, [recurrence data missing in n=30]) at median follow-up of 14 months (IQR 3-36). Median follow-up time was not significantly different between groups (ENDO: 17, ULT 12, UFT 14 months, p=0.66). In unadjusted analysis, recurrence rates were significantly different between surgery categories with 68% ENDO, 77% UFG and 84% ULT of patients being recurrence free at 12 months. Figure 

In the adjusted model, recurrence rates were significantly different between surgery categories, with women undergoing ULT having 65% less risk of recurrence compared to those undergoing endoscopic treatment. (ENDO: Ref ULT: HR 0.35 [95% CI 0.18-0.69], p=0.003) (UFG: HR 0.5 [95% CI 0.28-0.91], p=0.02) Table We also found that abnormal tissue quality was significantly associated with risk of recurrence (HR 1.99 [95% CI 1.05-3.79], p=0.04).
Interpretation of results
In this retrospective, multi-institutional study of 215 women who underwent surgical treatment for female urethral stricture we find that 65% of women remained stricture free at median follow-up of 14 months. On adjusted and unadjusted analysis, we find that time to recurrence was significantly different between surgical categories, with endoscopic management having the poorest outcomes with an unadjusted 12 month stricture recurrence free of 68%. 

Our data parallels prior data on outcomes of urethral stricture, showing the poorest outcomes among women treated with endoscopic management (27-58%). [1-2] Our UFG outcomes are also consistent with a 2019 retrospective, multi-institutional study of 39 women undergoing UFG (dorsal onlay, buccal mucosal graft) for urethral stricture, which found that 77% (n=23) of women remained stricture free, median time to recurrence was 14 months. [3] Our study reinforces these previous studies and together, this data supports the conclusion that endoscopic approaches to treatment of urethral stricture are less durable than urethroplasty.
Concluding message
This data provides the first, large, multicenter comparison of surgical outcomes for different approaches to female urethral stricture. We find that patients undergoing endoscopic management have significantly higher risk of recurrence compared to those undergoing either urethroplasty with local flap or free graft.
Figure 1 Kaplan-Meier Survival Curve: Unadjusted Time to Recurrence By Surgery Type
Figure 2 Table: Cox Proportional Hazard Model for Time to Female Stricture Recurrence
References
  1. Faiena I, Koprowski C, Tunuguntla H. Female Urethral Reconstruction. J. Urol. [Internet]. 2016;195:557–567. Available from: http://dx.doi.org/10.1016/j.juro.2015.07.124.
  2. Popat S, Zimmern PE. Long-term management of luminal urethral stricture in women. Int. Urogynecol. J. [Internet]. 2016;27:1735–1741. Available from: http://dx.doi.org/10.1007/s00192-016-3006-8.
  3. Hampson LA, Myers JB, Vanni AJ, et al. Dorsal buccal graft urethroplasty in female urethral stricture disease: a multi-center experience. Transl. Androl. Urol. [Internet]. 2019;8:S6–S12. Available from: http://dx.doi.org/10.21037/tau.2019.03.02.
Disclosures
Funding SUFU Research Network Clinical Trial No Subjects Human Ethics Committee Institutional Review Board at University of Michigan (and at each participating site) Helsinki Yes Informed Consent No
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