Randomized controlled trials (RCTs) are recognized as the gold standard methodology for health care outcomes research. It is one of the most reliable study designs, but proper adherence to rigorous methodological principles is paramount to ensure study validity. In general, RCTs require more time, cost, and resources to conduct compared to other study designs and can present logistical challenges.

Compared to other urologic subspecialties, reconstructive urology has a notable paucity of RCTs. A recent investigation revealed that of the available RCTs for urethroplasty, the quality of methodologic reporting was generally poor.¹

Why Are RCTs So Difficult to Perform in Reconstructive Urology?

There are far fewer reconstructive urologists in practice compared to other subspecialties (ie, oncology), and practice patterns are not standardized. Due to the diversity in training between reconstructive urologists, there is wide variation in surgical techniques and several ways to approach one problem. For many procedures, there is little available evidence to suggest superiority of one technical approach over another. This contributes to a difficult cycle: without available evidence, practice patterns will not shift; without standardized practice patterns, evidence is difficult to obtain.

Moreover, much of reconstructive urology is based on surgical intervention rather than pharmacologic treatment—further complicating the ease of trial development. Most reconstructive urologic studies (ie, urethral stricture disease [USD] or acquired buried penis) have been plagued with heterogenous patient populations and lack of defined primary end points, making comparison among studies difficult. In USD, for example, certain studies use objective outcomes such as anatomic patency, while others focus on subjective and patient-important outcomes such as International Prostate Symptom Score, postvoid residual, flow rate, or quality of life scores. To better study USD and acquired buried penis, recent classification systems have been developed to better compare homogenous groups of patients.^2,3

To combat this relative dearth of level 1 evidence, groups of reconstructive urologists like TURNS (Trauma and Reconstructive Network of Surgeons) have developed a database for purposes of information sharing and research. Recently, we (TURNS) attempted an RCT comparing dorsal vs ventral bulbar buccal mucosa graft urethroplasty. Despite our best efforts, the trial was halted due to lack of patient accrual. Many patients voiced their discomfort with the notion that their surgeon could be performing a surgical approach that differed from their personal practice pattern with an already high degree of success.

Despite these unique challenges, several pivotal trials have emerged in recent years furthering the field of reconstructive urology. We have chosen to highlight 2 RCTs from the last 5 years, each covering a different domain of reconstructive urology.

Incontinence

Abrams P, Constable LD, Cooper D, et al. Outcomes of a Noninferiority Randomised Controlled Trial of Surgery for Men With Urodynamic Stress Incontinence After Prostate Surgery (MASTER). Eur Urol. 2021;79(6):812-823.⁴

This was a nonblinded, multicenter, noninferiority study RCT comparing the male transobturator sling to the artificial urinary sphincter (AUS) among a cohort of men with postprostatectomy stress urinary incontinence. Randomization was performed in a 1:1 ratio with 190 men in each cohort. The primary outcome measure was patient-reported stress urinary incontinence 12 months postintervention.

At 12 months, incontinence rates in the sling cohort were 87.0% vs 84.2% in the AUS cohort (P_NI = .003).

Secondary outcomes included patient-reported outcomes from the International Consultation on Incontinence Questionnaire—Urinary Incontinence Short Form questionnaire, which found incontinence symptoms to be worse in the sling cohort (CI 0.2-2.6, P = .02). Satisfaction was much higher for patients in the AUS cohort (90.6% vs 72.2%, P < .001).

Key Points

• This study used a strict definition of incontinence based on patient-reported outcome measures.
• Pad weight and urodynamics findings were not reported.
• Although noninferiority was demonstrated, most secondary outcome measures favored the AUS (quality of life, pads per day, patient satisfaction, and likelihood to recommend the procedure to a friend).
• The sling cohort experienced no reduction in hospital length of stay and were more likely to undergo a repeat incontinence procedure.
• Follow-up of 12 months may not capture delayed complications and longitudinal impact on patient satisfaction.

USD

Goulao B, Carnell S, Shen J, et al. Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-Label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial). Eur Urol. 2020;78(4):572-580.⁵

This was a randomized, single-blind controlled trial of 222 men with recurrent bulbar strictures, recruited from 38 sites in the UK. Randomization was performed in a 1:1 ratio of urethroplasty—to—direct visualization internal urethrotomy. The primary outcome was voiding symptoms score on the Mundy Patient-Reported Outcome Measure (PROM) at 24 months.⁶

At 24 months, symptomatic improvement was similar between groups based on the PROM symptom score, ranging from 0 to 24 with higher number indicating worse symptoms (7.4 in urethroplasty group and 7.8 in direct visualization internal urethrotomy group, P = .6).

Secondary outcomes included objective measures, such as flow rate, stricture recurrence, and reintervention which all favored urethroplasty: maximum flow rate improvement by 10 mL/s or more: 19% vs 13% (P = .024); recurrence: 18% vs 35% (P = .001); reintervention: 14% vs 26% (P = .017).

Key Points

• PROM scores demonstrated no statistical difference between the 2 groups, but secondary objective outcomes all favored urethroplasty.
• Patients in the urethroplasty group were 48% less likely to require reintervention (P = .017), and time to reintervention was longer in the urethroplasty group, suggesting a more durable response.
• There was no strict definition of recurrence listed in the methodology of this study.

Although there are many barriers to conducting RCTs within the sphere of reconstructive urology, the above studies provide level 1 evidence with which we can counsel our patients. With thoughtful design and appropriate selection of patients and outcome measures, quality evidence is attainable. To contribute to the growing body of evidence in reconstructive urology, disease-specific classification and staging systems should be employed to study homogenous groups of patients, while RCTs should be attempted when feasible with emphasis on patient recruitment. Additionally, multi-institutional collaboration is vital to ensure results are applicable to diverse patient populations.