Preoperative and intraoperative factors predictive of complications and stricture recurrence following multiple urethroplasty techniques

Abstract Objectives To investigate factors predictive of postoperative recurrence and complications in patients undergoing urethroplasty for stricture repair at a single center. Patients and methods We retrospectively reviewed the records of 108 men who underwent urethroplasty for urethral stricture disease (USD) at a single center from 2016 to 2020. Demographic data, comorbidities, stricture history including etiology and prior treatments, patient‐reported symptoms, and outcomes data were collected for analysis. Data were analyzed in aggregate, then, stratified by type of urethroplasty performed. Descriptive statistics, univariate analysis, multivariate logistic regression, and intergroup comparisons were completed using STATA, with an alpha value of 0.05 and a confidence interval of 95%. Results The median age of our patients was 58 years (interquartile range: 42‐69; range: 29‐83), with a median stricture length of 2.0 cm (interquartile range: 1.0‐4.5; range: 0.5‐10). The most common stricture etiology was iatrogenic (n = 33, 31%) and the most common urethroplasty was anterior anastomotic urethroplasty (n = 38, 35%), followed by buccal mucosal graft (BMG) urethroplasty (n = 35, 32%). Twenty‐four patients (22%) had stricture recurrence. Within the aggregate data, recurrence was significantly predicted by obesity (BMI > 30) (Odds Ratio [OR] 3.2, 95% Confidence Interval [CI]: 1.06‐10), and the presence of postoperative complications (OR 6.3, CI: 1.9‐21). The presence of any postoperative complications within 90 days was significantly predicted by stricture length ≥ 5 cm (OR 3.5, CI 1.09‐12) and recurrence (OR 6.0, CI 1.7‐21). Conclusion Despite serving as the most definitive treatment for urethral stricture management, stricture recurrence and postoperative complications are not uncommon after urethroplasty. Obesity and stricture length negatively impact outcomes while a penile stricture location is associated with a lower recurrence rate, though this is not statistically significant.


| INTRODUC TI ON
Urethral stricture disease (USD) is narrowing of the urethra due to inflammation or trauma to the urethra which causes accumulation of scar tissue within the corpus spongiosum and urethral mucosa.
There are multiple etiologies for USD including idiopathic, iatrogenic, traumatic, congenital, and infectious. 1 Associated symptoms include urinary retention, bladder outlet obstruction, genitourinary pain, recurrent urinary tract infections (UTI), and ejaculatory dysfunction, all of which can negatively impact quality of life. 2 With prevalence estimates ranging from 229 to 627 per 100 000 men and as high as 0.6% in at-risk populations, 3 optimizing management and prevention of urethral strictures is an important, yet, understudied, area of research.
Urethroplasty is the most definitive management of urethral strictures, which involves urethral reconstruction through a variety of techniques that depend on the stricture size and location. 1, 4,5 These include direct excision and primary anastomosis of the strictured area, and/or the use of mucosal grafts or flaps to expand the urethral lumen. 6 Although urethroplasty has a lower recurrence rate than both urethral dilation and direct vision internal urethrotomy (DVIU) procedures, recurrence and complications are not uncommon. It is difficult to quantify recurrence rates after urethroplasty given the variability of stricture disease, the wide variety of surgical techniques, and the lack of uniformity in describing recurrence.
Nevertheless, large systematic reviews and smaller single-center studies have found that stricture recurrence rates over time range from 10% to 58% of patients after urethroplasty, but these have often been narrow in scope, analyzing only a single urethroplasty technique. [7][8][9][10] In addition, a number of patients experience postoperative complications such as urinary tract infections, urinary leakage, and wound-related issues. 11 Thus, despite the favorable outcomes for urethroplasty, there may be independent preoperative and perioperative factors that predict recurrence and complications.
In this retrospective analysis, we sought to investigate factors predictive of postoperative recurrence and complications in patients undergoing multiple urethroplasty techniques for stricture repair at a single center. We hypothesize that independent risk factors for stricture recurrence following urethroplasty include postoperative complications and stricture complexity (i.e., longer length).

| PATIENTS AND ME THODS
We retrospectively reviewed a prospectively gathered database of 188 males who were evaluated for USD by a single surgeon (ECO) at a single tertiary center (Dell Seton Medical Center at the University of Texas, Austin, Texas) from 2016 to 2020. Depending on stricture length and location, patients underwent a variety of surgical procedures for their stricture disease based on surgeon recommendation.
Anastomotic urethroplasty, posterior urethroplasty, perineal urethrostomy, and meatoplasty were carried out in relatively standard fashions as previously described. 12 Substitution urethroplasty (using buccal mucosal grafting [BMG] in dorsal onlay, ventral onlay, and dorsal augmented anastomotic fashions) was carried out as described in the literature. 13 No skin flaps were used in the penile strictures, and all BMG urethroplasties for penile strictures were dorsal onlay. No ASOPA or inlay techniques were used. Patients were included in our analysis if they underwent one of these operative interventions at our facility for their USD. All patients who did not undergo urethroplasty and those with less than 30 days of postoperative follow-up at the time of data collection were excluded, reducing our final cohort to 108 men ( Figure 1). Demographic, clinical, and outcomes data were collected for analysis. Age was recorded, and an inflection point of 55 years was used for regression analysis. Comorbidities including diabetes mellitus, obesity, coronary artery disease, prostate cancer, and smoking history were recorded. Stricture history, including etiology (idiopathic, iatrogenic, lichen sclerosus, and traumatic) and prior treatments with DVIU, dilation, and/or prior urethroplasty were recorded. Stricture length and location were reported based on retrograde urethrogram imaging interpretation and/or intraoperative length measurement (cm). Patient symptoms at presentation were assessed objectively with the AUA Symptom score.
Recurrent UTI was noted if the patient had two or more UTIs in the last 6 months, or three or more UTIs in the last 12 months.

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A descriptive analysis was performed using variables related to medical history, presenting symptoms, stricture characteristics, and clinical outcomes. Continuous variables were summarized using median and interquartile range and compared using two sample t test.
Age and stricture length were dichotomized for regression analysis at inflection points of 55 years and 5 cm, respectively. Unadjusted differences were identified using univariate analysis via Chi-squared test or Fisher's exact test as indicated. Significance was defined with an Pvalue less than 0.05, and predictors with a P-value < .25 were included in the multivariate logistical regression analysis to control for potential confounders. To assess the performance of the model, calibration was tested with the Hosmer-Lemeshow (HL) test and discrimination was tested with receiver operating characteristic (ROC) curve analysis. Data were analyzed in aggregate, then, stratified by the type of urethroplasty performed. Statistical analyses were carried out using R-Studio (Boston, MA, USA) statistical software. Institutional review board permission was granted for this study.
Aggregate stricture recurrence was analyzed with univariate analysis (Table S2), demonstrating significant association with postoperative complications (P = .01). On multivariate analysis (

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First, obesity was a significant predictor of recurrence in both the overall cohort (OR 3.2) and in patients who received an anterior anastomotic urethroplasty (OR 1.47). This is corroborated by evidence on the known perioperative risks and comorbidities associated with a BMI > 30, 15,16 and this is in line with previous studies. Chapman et al. found obesity to be an independent predictor of stricture recurrence in a study of 596 patients who underwent isolated bulbar urethroplasty. 17 Breyer et al found that a BMI between 25 and 35 was significantly predictive of urethroplasty failure on univariate analysis of a cohort of 381 patients. 18 However, neither study was able to investigate obesity on multivariate analysis to isolate its impact away from confounders like diabetes and cardiac disease or compare the impact of obesity across multiple urethroplasty types.
While there is no singular explanation for why obesity may increase perioperative risk, obesity has been associated with systemic chronic low-grade inflammation, impaired collagen regeneration, and vascular insufficiency, all of which may contribute to urethroplasty failure and stricture recurrence. 19,20 Obesity may also impair surgical exposure and thus negatively impact the technical feasibility of an operation, particularly in patients with proximal bulbar strictures. 18 Furthermore, a large suprapubic fat pad can lead to a buried penis and create an environment conducive to chronic inflammation and lichen sclerosus, potentially causing or worsening a urethral stricture. 21 Interestingly, in Breyer's study, a BMI above 35 was not significantly associated with recurrence, unlike the current study. The authors attribute this to the more sedentary lifestyles of morbidly obese patients, which result in avoidance of activities that impair urethroplasty outcomes. 18

Pvalue
Medical history   9 Our subgroup analyses are also underpowered, so it is impossible to draw strong conclusions from the findings as they are presented here.
Despite these limitations, this study is the first comprehensive review of outcomes across multiple urethroplasty types, with the inclusion of predictive variables including demographics, comorbidities, and stricture characteristics. Our results have elucidated several statistically significant predictive factors that could influence urethroplasty technique selection, preoperative patient optimization, patient education, and expectation-setting prior to urethroplasty.
Going forward, we hope to provide the reconstructive surgeon an enhanced understanding of the utility and risk profiles of the multiple techniques in their armamentarium, as well as the predictors for recurrence and complications which may prove valuable in improving overall treatment outcomes and patient satisfaction.

| CON CLUS ION
Despite serving as the most definitive treatment for urethral stricture management, stricture recurrence and postoperative complications are not uncommon after urethroplasty. This 4-year retrospective study establishes predictive factors for complications and recurrence following urethroplasty. Future directions include a focus on patient-reported outcomes and how stricture recurrence impacts patient satisfaction.

CO N FLI C T O F I NTE R E S T
The authors have no other personal or institutional interest with regards to the authorship and/or publication of this manuscript.