Posterior urethral stenosis: a comparative review of the guidelines

Purpose We aimed to provide a thorough comparative review of the available guidelines on the diagnosis, management, and follow-up for patients with posterior urethral stenosis by the American Urologic Association (2016), Société Internationale d’Urologie (2010), and European Urologic Association (2022). Methods The AUA, SIU, and EAU guidelines were evaluated for recommendations on the diagnosis, evaluation, and treatment of posterior urethral stenosis. We also included the EAU and AUA urologic trauma guidelines for the trauma-related stenosis. The level or strength of recommendations is included in case of disparity between the guidelines. Results The three guidelines align considerably in recommendations provided for the diagnosis, management, and follow-up of patients with posterior urethral stenosis. SIU and EAU emphasize the role of repeat endoscopic treatment in guidelines compared to AUA. Conclusion The preferred method to repair bulbo-membranous stricture/stenosis following radiation therapy remains an area of active interest, focusing on continence preservation. Additionally, there may be a role for advanced endoscopic treatments with or without adjunct therapies to manage even obliterated stenoses. Supplementary Information The online version contains supplementary material available at 10.1007/s00345-022-04131-y.


Introduction
Urethral stricture is an abnormal narrowing of the urethra resultant from fibrosis in the spongiosus tissue surrounding the anterior urethra [1]. In the posterior urethra -extending from bladder neck to membranous urethra-a 'stenosis' is the preferred term because the segment lacks spongiosal tissue [1,2]. The majority of urethral stricture occurs in the anterior urethra (92%), leaving the posterior stenoses relatively understudied [3].
Posterior urethral stenosis may occur iatrogenically, most notably due to treatment for benign prostatic hypertrophy (BPH) and prostate cancer [1,2]. Pelvic fracture urethral injuries (PFUI) represent a well-described traumatic etiology for posterior urethral stenosis. Based on etiology and current patient anatomy, posterior urethral stenosis is treated with various procedures ranging from catheterization to abdominoperineal reconstruction.
Formerly, Société Internationale d'Urologie (SIU) and American Urologic Association (AUA) had published guidelines on the evaluation, management, and follow-up for urethral strictures, respectively in 2010 and 2016 [4,5]. Similarly, the European Urologic Association (EAU) recently published guidelines for evaluating and managing posterior urethral stenosis [6]. Our group had previously published a review article to compare the guidelines provided by AUA and SIU on urethral stricture and stenosis [7]. With updated guidelines, we aimed to provide an in-depth review to compare the AUA, SIU, and EAU guidelines for assessment, management, and follow-up of patients with posterior urethral stenosis. This work is the second of this series, preceded by a review article comparing the latest guidelines on anterior urethral stricture [8].

Methods
The SIU, AUA, and EAU guidelines were evaluated for recommendations on the diagnosis, evaluation, and treatment of posterior urethral stenosis. For the trauma-related stenosis, we additionally included the EAU and AUA urologic trauma guidelines as, unlike the SIU urethral stricture guideline, the EAU and AUA stricture guidelines did not provide suggestions for the diagnosis and management of trauma-related urethral injuries [9,10].
The level or strength of recommendations is included in case of disparity between the guidelines. The EAU and SIU guidelines have adopted the Oxford classification system, while AUA has developed a distinct evidence-grading system [7]. SIU stratified their recommendation strength from A to D based on the level of evidence [4]. The EAU guidelines recommendations are based on a modified GRADE methodology considering the level of evidence, the magnitude of effect, certainty of the results, the balance between desirable and undesirable outcomes, and the impact/certainty of patient values and preferences [6,11,12]. AUA approaches the strength of the recommendations based on evidence strength, certainty level, the magnitude of benefit or risk/burdens, and the Panel's judgment regarding the benefits and risks/burdens [5] (see appendix).

Non-traumatic posterior urethral stenosis
Posterior urethral stenosis can result from iatrogenic causes, including trans-urethral resection of the prostate (TURP) for BPH, radiation/high energy therapies, or open/robotic surgeries to treat prostate cancer [1,2]. Treatments for nontraumatic posterior stenoses include conservative management as well as endo-luminal and (minimally) invasive interventions [6]. Optimal treatment and timing, however, are individualized based on the patient's situation.
The pre-operative evaluation should include a history, physical examination, and post-void residue (PVR) measurement [SIU: A]. Urine analysis/culture and sensitivity/leukocyte esterase screening test, as well as blood urea nitrogen, creatinine, glucose, and PSA measurement, could be used adjunctively [SIU: B]. Cystoscopy is currently considered the optimum imaging modality for pre-operative evaluation of posterior stenoses, which could guide treatment [SIU: B]; particularly in case of a combination of anterior stricture and posterior stenosis. Further, urodynamics could be used to evaluate voiding dysfunction and/or urinary incontinence [SIU: C].
Recommendations for iatrogenic, non-traumatic posterior urethral reconstruction treatment are based on the etiology and the location of stricture/stenosis. Posterior urethral stenosis following iatrogenic injury (e.g., post-TURP)

Bladder neck contracture (BNC)
In patients with non-obliterative stenosis in the bladder neck due to BPH surgeries, the surgeon should perform either trans-urethral resection (TUR) or hot-knife direct vision internal urethrotomy (DVIU) as the first-line modality [AUA: Expert opinion; EAU: Strong] (Fig. 1). Dilation could also be opted as the primary intervention according to AUA [AUA: Expert Opinion]; however, dilation is not included in EAU guidelines for BNC management (

BNC/Prostatic urethral stenoses
The most crucial consideration for bladder neck/prostatic urethral stenosis is whether there is a lumen. If there is no lumen, the stenosis is considered "obliterated". The guidelines, particularly EAU, treat these as more severe cases with limited management options. For obliterative BNC, the EAU discourages endo-luminal procedures and early treatment with open reconstruction or diversion [EAU: Strong]. This recommendation and the strength of evidence are based on the near certainty of recurrence for endo-luminal treatment in this cohort.
For non-obliterative stenoses, the SIU recommends initial stenosis management with dilation, followed by cold/ hot-knife DVIU or TUR combined with/without intermittent self-dilation (ISD) [SIU: C]. In case of primary DVIU/TUR failure, TUR should be performed/repeated once [SIU: C]. This differs from the EAU guidelines, which suggest a role for repetitive endo-luminal treatment for non-obliterative BNC to stabilize patency [EAU: Strong]. Growing evidence supports the efficacy of intralesional corticosteroids or mitomycin C injection during endo-luminal procedures to reduce the risk of recurrence in these patients [13][14][15][16][17]. However, no specific recommendation has been made by any of the guidelines in this regard.
The AUA and SIU agree on open reconstruction for recalcitrant radiation-induced BNC [AUA: Conditional; SIU: C], while the SIU uniquely offers posterior stenting (UroLume ® ) or supra-pubic/-vesical urinary diversion for non-urethroplasty candidates [SIU: C] (Fig. 2). Recently, robotic reconstruction for recalcitrant cases has been described, allowing for minimal incisions, reduced blood loss and post-operative pain, and shorter hospitalization and recovery [18][19][20][21]. Despite this, none of the guidelines have specifically addressed the use of robotic procedures for urethral stricture.
Lastly, salvage prostatectomy could be considered for medically fit patients with proper bladder function diagnosed with radiation-induced prostatic stricture [EAU: Weak].    (Fig. 3). For incontinent patients, re-do vesico-urethral anastomosis could be approached retropubicly, and patients must be warned of the high risk of urinary incontinence if transperineal approach is being considered. According to SIU, urinary diversion should be considered for previously incontinent patients with obliterative stenosis.

Bulbomembranous/membranous strictures
Guidelines agree that urinary incontinence correction can be considered following resolution of obstruction, though the EAU discourages intervention prior to six months following re-do vesico-urethral anastomosis.

Complex scenarios
For complex or recalcitrant stenosis, urinary diversion could be performed in patients with incapacitated bladder and/or disabling local symptoms [EAU: Weak]. Further, cystectomy could be considered in patients with incurable bladder pain/spasms and/or intractable hematuria [EAU: Weak].

Trauma-related urethral stenosis
PFUI occurs in 1.6% to 25% of all pelvic fractures. However, the pelvic fractures leading to PFUI are significant, with 5% to 33% mortality [24]. Mechanistically, the term PFUI is applicable when the urethra is avulsed at the perineal membrane level, the point that membranous and bulbar urethras join [24,25]. Avulsion may cause complete or partial urethral disruption and significant damage to the urethral sphincter [24,26]. Given the extensive experience with traumatic posterior urethral injuries, we also include a short segment of the Urology Society of India Guidelines (USI) for this pathology.
According to AUA, the presentation of blood at the urethral meatus in patients with pelvic trauma indicates evaluation for PFUI (i.e., RUG). However, SIU suggests that even in the absence of classic signs of urethral injury (e.g., blood at the meatus and/or voiding difficulty) [24], fractures disrupting the pelvic ring are highly suggestive of concomitant urethral injuries [SIU: A]. Therefore, PFUI must be ruled out in all such pelvic fracture cases [SIU: A]. Palpable bladder and 'high-riding prostate during digital rectal examination (DRE) are suggested as signs in favor of PFUI diagnosis [24]. However, SIU discourages the use of DRE as a diagnostic tool for PFUI, although it may be helpful in the evaluation of rectal injuries associated with pelvic fractures [SIU: B]. RUG is currently considered the gold standard for PFUI assessment [AUA; SIU: A]. An optimal RUG is performed by an experienced technician, envisioning the whole length of the urethra (including the bladder neck) to detect the site and stage of the injury [SIU: A]. EAU suggests flexible cystourethroscopy and/or RUG to evaluate male urethral injury and cystourethroscopy and vaginoscopy for the evaluation of female urethral injury. [EAU: Strong].

Management
PFUIs could be managed either primarily or in a delayed fashion, implementing various techniques. While a full review of PFUI management is not in the scope of this review, those recommendations that have made it into

Initial management
The guidelines unanimously recommend early bladder drainage as the patient could benefit through primary prevention of urinary extravasation and retention [24]. Drainage can be achieved by either supra-pubic or trans-urethral fashion, as it seems unlikely to induce additional damage to the urethra [SIU: A; EAU: Strong] [24]. However, while EAU does not consider either approach superior to the other, the SIU, AUA, and the USI guidelines name supra-pubic catheterization as the initial management of choice in most PFUI patients, which could be performed percutaneously under ultrasonographic guidance or during an emergent laparotomy [AUA: Expert opinion; SIU: A].

Early management
In patients with failed urethral catheterization or those treated with primary supra-pubic catheter placement, the guidelines generally favor early endoscopic urethral realignment after stabilizing hemodynamics. The early realignment minimizes extravasation of urine in partial injuries, while in complete defects, it is performed as an effort to reattach severely distracted ends rather than preventing the latecoming strictures [27]. A surgeon may opt for a variety of techniques for endoscopic realignment based on the surgeon's expertise and the available instruments, ranging from simple retrograde catheterization to endoscopic procedures involving cystoscopy and retrograde guidewire passage or simultaneous use of flexible and rigid cystoscopes passed antegrade or retrograde. However, the clinicians must avoid prolonged endoscopic realignment attempts [AUA: Clinical Principle] as well as repeating endoscopic modalities following failure at realignment [EAU: Strong]. After successful urethral catheterization/realignment, the catheter should be maintained for 3 to 6 weeks [SIU: B]. There is some evidence to suggest that early endoscopic realignment may prevent stricture in future [28]. There are ongoing studies, including a randomized controlled trial, to evaluate the durability of this effect [29,30].
Although immediate open urethroplasty should be avoided in patients with PFUI, EAU recommends early urethroplasty (from two days to six weeks) in selected patients who are stable and have a short gap between the urethral ends as well as soft perineum when the lithotomy approach is feasible [EAU: Strong]. Moreover, urethroplasty should be performed within seven days for female patients with PFUI, and realignment is not indicated [EAU: Strong].

Delayed management
Endoscopic dilation or DVIU can be attempted once for short non-obliterative stenoses [EAU: Weak]. Repetitive endoscopic treatments are associated with complications and likely not curative [31]. However, surgeons should choose urethroplasty over endoscopy if delayed management is being considered for completely obliterated stenoses due to pelvic fractures [AUA: Expert opinion; EAU: Strong] as endo-luminal treatments are primarily unsuccessful and may falsely pass through the bladder or rectum [6].
Reconstructive surgeries should be considered only after the stabilization of major accompanying injuries and per- In cases of 'gapometry/urethrometry index' -which is measured by dividing the length of the urethral gap by the length of the bulbar urethra-being below 0.35, a urethral gap over 2.5 cm, or prostatic lateral displacement, the progressive perineal approach may be insufficient, and the surgeon should consider elaborated perineal or trans-pubic repair [SIU: B]. However, one should reserve an abdominoperineal approach for more complicated scenarios, namely in cases of highly long distraction defect, para-urethral fistula at the base of the bladder, recto-urethral fistula related to trauma, and injury of the bladder [EAU: Weak]. Total pubectomy is discouraged during abdominoperineal repair [EAU: Strong], while bladder neck repair could be done simultaneously [SIU: C].
Post-traumatic urethral fistulas should be managed based on the location and etiology taking into account surgical expertise. The fistula should fully be exposed through a proper surgical approach, excised completely, and reconstructed with a well-vascularized flap [SIU: B]. For example, recto-urethral fistulas could be approached abdomino-perineally, and tissue flaps from the gracilis or rectus muscles could be used to fill the dead spaces [EAU: Weak].

Complications
Post-traumatic urinary incontinence could be managed by urethral slings, artificial urinary sphincters, urinary diversion, or bladder neck reconstruction.
However, patient selection is of utmost importance [SIU: B]. Moreover, trauma-related ED may be alleviated with the early use of phosphodiesterase type 5 (PDE5) inhibitors [SIU: C]. More advanced treatment of ED may be required, particularly as many patients with PFUI are young. Finally, the potential damage to the internal and external sphincter mechanisms should always be evaluated in PFUIs [SIU: A].

Conclusion
The recommendations provided by the three guidelines align considerably for the diagnosis, management, and follow-up of patients with posterior urethral stenosis. There remains a more prominent role for repeat endoscopic treatment in SIU and EAU guidelines compared to AUA. The preferred method to repair bulbo-membranous stricture/stenosis following radiation therapy remains an area of active interest, with a particular focus on continence preservation. Additionally, there may be a role for advanced endoscopic treatments with or without adjunct therapies to manage even obliterated stenoses.

Conflicts of interest
The authors have no relevant financial or nonfinancial interests to disclose.

Research involving human participants and/or animals This study does not contain any human participants and/or animals.
Informed consent Our study does not contain human subjects.
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