Deep Phenotyping the Anterior Urethral Stricture: Characterizing the Relationship Between Inflammation, Fibrosis, Patient History, and Disease Pathophysiology

Abstract

Purpose: Anterior urethral stricture disease (aUSD) is a complex, heterogeneous condition that is idiopathic in origin for most men. This gap in knowledge rarely affects the current management strategy for aUSD, as urethroplasty does not generally consider etiology. However, as we transition towards personalized, minimally invasive treatments for aUSD and begin to consider aUSD prevention strategies, disease pathophysiology will become increasingly important. The purpose of this study was to perform a deep phenotype of men undergoing anterior urethroplasty for aUSD. We hypothesized that unique biologic signatures and potential targets for intervention would emerge based on stricture presence/absence, stricture etiology, and the presence/absence of stricture inflammation. Materials and Methods: Men with aUSD undergoing urethroplasty were recruited from one of 5 participating centers. Enrollees provided urethral stricture tissue and blood/serum on the day of surgery and completed patient-reported outcome measure questionnaires both pre-and postoperatively. The initial study had 3 aims: (1) to determine pediatric and adult subacute and repeated perineal trauma (SRPT) exposures using a study-specific SRPT questionnaire, (2) to determine the degree of inflammation and fibrosis in aUSD and peri-aUSD (normal urethra) tissue, and (3)

Editorial Comment

“…In the Trauma and Urologic Reconstruction Network of Surgeons prospective database, the short (L1/L2), proximal/midbulbar (S1a) urethral strictures of idiopathic origin (E2) make up over half of the nearly 3000 strictures in the cohort. 1 While this area is certainly vulnerable DEEP PHENOTYPING THE ANTERIOR URETHRAL STRICTURE…”

“…This multi-institutional study of urethral stricture etiology aims to identify phenotypic signatures among variable presentations of the disease. 1 Using a combination of patient-reported characteristics, serum inflammatory profiles, and histology, the authors demonstrated an association between clinical etiology and biological profiles. Although all stricture patients had a background elevation in systemic inflammatory markers, the histologic signature of idiopathic strictures resembled that of inflammatory lichen sclerosus more often than traumatic strictures.…”