This document was created in August 2023 for original publication into the AUA Medical Student Curriculum. This document will continue to be periodically updated to reflect the growing body of literature related to this topic.

URETHRAL STRICTURE DISEASE

KEYWORDS: Urethral stricture, urethral imaging, endoscopic instrumentation, urethroplasty, perineal urethrostomy.

LEARNING OBJECTIVES

At the end of medical school, the medical student will be able to…

1. Understand the anatomy of the urethra and identify notable anatomical landmarks.
2. Discuss the etiology and pathophysiology of urethral stricture disease.
3. Discuss the progression and state the complications of untreated urethral stricture disease.
4. Describe the epidemiological features of urethral stricture disease, including risk factors, pertinent patient demographics, and associated costs to the healthcare system.
5. Describe the process of diagnosing urethral stricture disease based on patient symptoms, the clinical history and physical exam, and pertinent imaging studies.
6. List and discuss major surgical treatment options for urethral stricture disease.

Basic Urethral Anatomy and Correlations to Stricture Disease

The anterior urethra consists of the urethral meatus, fossa navicularis, penile urethra, and bulbar urethra, which are all surrounded by corpus spongiosum; whereas the posterior urethra consists of the membranous and prostatic urethra (Figure 1).¹ A urethral stricture is an abnormal narrowing of the anterior urethral lumen due to fibrosis or scarring of the urothelium, but may also involve the corpus spongiosum.^2,3 Formation of scar tissue in the posterior urethra, which does not have a corpus spongiosum, is known as urethral stenosis and is characterized by narrowing of the membranous or prostatic urethra. Stenosis of the bladder neck is called bladder neck contracture if caused by prostate outlet surgery or radiotherapy, or vesicourethral anastomotic stenosis if it is the result of an open or robotic radical prostatectomy.⁴

Figure 1: Review of urethral anatomy. The membranous urethra is the boundary structure that differentiates the anterior urethra (structures 1-4) from the posterior urethra (structures 5-6). Figure adapted from (Tonkin and Jordan, 2009).¹

Males are more likely to experience a urethral stricture than females due to the presence of a longer urethra. In the United States, the incidence of male urethral strictures has been reported to be as high as 0.6%, resulting in more than 5,000 inpatient visits yearly and a healthcare cost of nearly $200 million.⁵

Pathophysiology of Urethral Stricture Formation and Progression

Injury to the urethral epithelium, known as the urothelium, and/or underlying corpus spongiosum is the basis of anterior urethral stricture development (Figure 2).⁶ The urothelium is normally composed of pseudostratified columnar epithelial cells, and injury to the tissue leads to squamous metaplasia.^2,6 The stratified squamous epithelium is more fragile than the pseudo-stratified columnar epithelium, and is thus more susceptible to splitting when distended during voiding.² Tears and fissures within the damaged, metaplastic urethra allow for urinary extravasation, which induces a fibrotic reaction within the spongiosum.^2,6 As the fibrosis progresses and the fibrotic plaques coalesce, the urethral lumen narrows and may potentially lead to symptomatic obstructive voiding symptoms seen in urethral strictures.^2,6

Figure 2: Urethral stricture disease pathophysiology. A) Fissures in the squamous metaplastic tissue allow for urinary extravasation, which induces a fibrotic reaction. B) Progressive fibrosis leads to a narrowing of the urethral lumen. C) As fibrosis progresses and fibrotic plaques coalesce, the result is spongiofibrosis. D) Extra-urethral spongiofibrosis that results from untreated urethral stricture disease and can cause obstructive voiding symptoms. Figure adapted from (Hampson, McAninch, and Breyer, 2014).⁶

Etiology and Risk Factors for Urethral Stricture Disease

The risk of experiencing a urethral stricture increases with age, with the highest incidence seen in individuals older than 65 years.^2,5 Common known causes of urethral injury include trauma to the perineum or urethra, as seen in straddle injuries and pelvic fractures; iatrogenic causes, such as pelvic radiation, surgery for hypospadias, urethral catheterization, and endoscopic procedures; infections, primarily recurring chlamydial or gonococcal sexually transmitted infections; and inflammatory pathologies, such as lichen sclerosus.^5,6 Generally, the leading causes of penile urethral strictures are iatrogenic and inflammatory pathologies, followed by idiopathic and traumatic etiologies.⁵ The leading causes of bulbar urethral strictures, in order of prevalence, are idiopathic, iatrogenic, traumatic, and inflammatory conditions.⁵

Clinical Presentation of Urethral Stricture Disease

Patients with symptomatic urethral strictures typically present with lower urinary tract symptoms consistent with obstruction, such as slow stream, dysuria, spraying, straining, terminal or postmicturition dribbling, incomplete emptying with a potential for urinary retention, and hematuria.^6,7 If the stricture has been present for a long duration of time, patients may experience recurring urinary tract infections, prostatitis, or even bladder stones.⁶ Strictures may also affect sexual function causing pain with ejaculation with delayed discharge of ejaculate.⁶ Thus, urethral strictures should be considered in the differential diagnosis for patients who present with such symptoms.³ It is essential to obtain a thorough history from the patient, particularly in terms of urinary and sexual function. Questionnaires that evaluate patient-reported outcome measures can be utilized to help assess urinary and sexual function before and after treatment of stricture disease.^8,9 Importantly, a urinalysis should be performed in conjunction with a history and physical examination to rule out an ongoing urinary tract infection.³

While the physical examination may not provide additional insight into the diagnosis of the stricture, the penis, scrotum, vagina, and perineum should be examined thoroughly; as non-hair-bearing skin or mucosa from these regions can be used for urethral reconstruction.¹⁰ Additionally, the mouth should be examined if the use of a buccal graft for reconstruction is suggested.¹⁰ It is important to palpate the anterior urethra to estimate the depth and density of the scar tissue.⁶ Examining the penis can also provide insight into undiagnosed lichen sclerosus, a known risk factor for urethral strictures, which may present as phimosis or a shiny, wrinkly, white-colored mucosa near the urethral meatus (Figure 3).²

Formal Diagnosis of Urethral Stricture Disease

Significant urethral strictures that cause obstructive symptoms can be detected on uroflowmetry, which will show a long, protracted flow pattern with a plateau appearance.² Pertinent parameters of interest include the maximal flow rate (Q_m) and average flow rate (Q_a), both of which will be reduced for age, and Q_m - Q_a.^11,12 For patients with slow stream and decreased urinary output, a bladder ultrasound may show an elevated post-void residual.⁶ Thus, the initial evaluation of a suspected urethral stricture should include patient-reported measures, uroflowmetry, and ultrasound post-void residual assessment.³

If obstructive voiding symptoms are present, along with a reduced flow rate on uroflowmetry +/- an elevated post-void residual volume on bladder ultrasound, further evaluation of the urethra using imaging modalities is indicated.³ Imaging studies are essential not only to diagnose the stricture, but also to assess the length of the stricture, which can inform operative planning.^3,6 A retrograde urethrogram (RUG) and voiding cystourethrogram (VCUG) can be used to view the full length of the urethra.^2,6 While VCUG alone is not sufficient to delineate the full male urethra, it can effectively visualize the entire female urethra.³ If VCUG and RUG cannot provide a definitive diagnosis of urethral stricture disease, cystoscopy, also known as urethroscopy, can elucidate the characteristics of a stricture.¹³ Urethral ultrasound is also an acceptable, though less common, method of evaluating stricture disease. These studies can help identify the stricture and determine its location, length, and severity; with visible narrowing present in the urethral lumen at the site of the stricture (Figure 4 and Figure 5).⁶

Figure 4: Identification of a urethral stricture using cystoscopy (A), retrograde urethrogram (B), and voiding cystourethrogram (C). Gray-scale ultrasound (D) and contrast-enhanced ultrasound (E) of the urethra can also evaluate stricture disease.

Figures were provided as a courtesy by Dr. Paul H. Chung, Thomas Jefferson University, Philadelphia, PA.

Figure 5: Localization of urethral strictures using retrograde urethrogram. A) Urethrogram from a patient with a bulbar urethral stricture, with the arrowhead indicating the region of interest. B) Urethrogram from a patient with a penile urethral stricture, with the arrowhead indicating the region of interest. C) Urethrogram from a patient with a panurethral stricture.

Figures were provided as a courtesy by Dr. Alex J. Vanni, Lahey Hospital and Medical Center, Burlington, MA.

In patients with an indwelling suprapubic cystotomy tube, which is commonly placed for urinary retention when urethral catheterization is infeasible, concurrent RUG and antegrade cystoscopy can clarify pertinent features of the stricture.^6,13 Antegrade cystoscopy is particularly useful in evaluating patients with posterior urethral stenoses, such as patients with a history of prostate radiation, as prostate radiation can lead to strictures of the membranous urethra, as well as pathology of the prostatic urethra, bladder neck, and bladder.^13,14

Complications of Untreated Urethral Stricture Disease

Complications of untreated urethral stricture disease can develop as a result of structural and functional changes to the urinary bladder and proximal urethra. RUG and VCUG may show a dilated proximal urethral segment, and an overdistended urinary bladder may manifest with elevated post-void residual volume.^15,16 Common complications of untreated stricture disease include bladder hypertrophy, urinary retention, hydronephrosis, recurrent urinary tract infections, prostatitis, epididymo-orchitis, periurethral abscess, and stones in the bladder or urethra.^2,16 Less frequent complications include the formation of one or more urinary bladder diverticula, the development of vesicoureteral reflux that may be unilateral or bilateral, and the formation of a urethrocutaneous fistula.¹⁶

Treatment of Urethral Stricture Disease

Endoscopic Management: Urethral Dilation and Direct Visual Internal Urethrotomy

Endoscopic management of urethral strictures by urethral dilation or direct visual internal urethrotomy (DVIU) is a pertinent option in patients presenting with a first-time, short bulbar urethral stricture (< 2 cm).^2,3 Urethral dilation can be performed with a variety of instruments or with catheterization.⁶ Sequential dilation can be performed using metal sounds and filiform and followers, although these are rigid tools that have an increased risk of causing additional trauma and resultant spongiofibrosis in the urethra (Figure 6A-C).¹⁷ Balloon dilators apply a radial force on the stricture with less trauma to the urethral tissue than rigid dilators and may be performed endoscopically or fluoroscopically (Figure 6D).¹⁷ More recently, a paclitaxel-coated urethral dilating balloon has been developed and is indicated for patients with recurrent bulbar strictures.¹⁸ Endoscopic visualization with a rigid cystoscope allows for the urologist to directly proceed with DVIU.^2,3 Briefly, DVIU involves a cold-knife transurethral incision that releases the scar tissue, which allows the open wound to heal at a larger caliber.⁶

Figure 6: Surgical instruments used in urethral dilation. A) Metal sounds arranged, left to right, in increasing size of diameter; B)-C) filiform dilators, with followers (B) and leaders (C); and D) UrethraMax balloon dilator (above) and coude tip catheter (below) in inflated states. Figure 6A-6C adapted from (Heyns, 2013), and figure 6D adapted from (MacDiarmid et al., 2000).^19,20

Generally, urethral dilatation is preferred over DVIU in strictures of the meatus, fossa navicularis, and penile urethra due to the relatively thin nature of the corpus spongiosum of the penile urethra; whereas DVIU is more frequently performed in the bulbar urethra.² However, studies have shown that urethral dilation and DVIU have comparable outcomes in terms of stricture-free rates, time to recurrence, and complications.^3,6,21 After a single dilation or DVIU that was not complicated by re-formation of the stricture within three months, the stricture-free rate was 55-60% at 24 months and 50-60% at 48 months.²¹ Stricture-free rates were lower for patients requiring a second or third dilation or DVIU for stricture recurrence within 3-6 months of the initial procedure.²¹ The highest success rates have been seen in bulbar urethral strictures that are < 1.5 cm and are not associated with spongiofibrosis.⁶ Conversely, the presence of prior endoscopic instrumentation, stricture recurrence, strictures longer than 2 cm, numerous strictures, strictures located in the penile or membranous urethra, urinary tract infections at the time of surgery, and spongiofibrosis are risk factors for recurrence.⁶ In addition to stricture recurrence, notable complications of urethral dilation and DVIU are bleeding, infection, incontinence, and reduced sexual function, among others.²²

A recent randomized controlled trial showed that the paclitaxel-coated urethral dilating balloon is safe and superior to both DVIU and urethral dilation approaches in patients with recurrent bulbar urethral strictures < 3 cm in length.¹⁸ The ROBUST I study showed a 67% functional success rate for the paclitaxel-coated urethral dilating balloon, which was defined as a > 50% reduction in the International Prostate Symptom Score without a need for retreatment.²³ Overall freedom from retreatment with the paclitaxel-coated urethral dilating balloon device was 77% at the conclusion of the three-year follow-up period.²³

Urethroplasty

Urethroplasty is the gold standard treatment for the initial management of urethral strictures, regardless of the location or length of the stricture, and should be strongly considered in patients with recurrent strictures following failed urethral dilation or DVIU.³ The length, location, and surgeon experience are important factors that determine the type of reconstruction that is performed.   

Urethral reconstruction can be categorized as an anastomotic and/or augmentation procedure. For short bulbar strictures (typically less than 2 cm), anastomotic urethral reconstruction may be performed as either an excision and primary anastomosis (EPA) or non-transecting anastomotic urethroplasty.³ EPA involves excision of the stricture followed by end-to-end anastomosis of the remaining healthy urethra (Figure 7).²⁴ Reconstruction with a graft or skin flap is preferred for penile strictures and bulbar urethral strictures that are > 2 cm in length.³ The most common graft used in urethral reconstruction is buccal mucosa, although grafts can be used from genital and non-genital skin, or lingual/bladder/rectal regions.² Fasciocutaneous flaps harvested from preputial or penile skin can be used to augment anterior urethral strictures with outcomes similar to the buccal mucosa graft, although with a higher complication rate.³

Figure 7: End-to-end urethral anastomosis after the excision of a urethral stricture. A) Dorsal urethral anastomosis involves the connection of the urethral mucosa and spongiosum. B) Ventral urethral anastomosis includes the urethral mucosa (not shown), followed by the closure of the spongiosum tunica over urethral mucosal anastomosis. Figure adapted from (Santucci, Mario, and McAninch, 2002).²⁴

In patients with recurrent bulbar strictures > 4 cm, urethroplasty has been shown to be successful in 80-90% of patients, while endoscopic approaches have yielded success rates of approximately 20%.^4,25 Among patients with complex or recurrent strictures in the meatus or navicular fossa, urethroplasty with extended meatotomy has shown strong success rates of up to 87%.²⁶ In terms of graft type, buccal mucosa grafting has a strong evidence base and the best outcomes for penile and bulbar strictures, while skin flaps have shown success in fossa navicularis strictures and penile strictures.²⁷ Complications of anastomotic urethroplasty have been reported in 6% of patients, and include transient thigh numbness (2%), wound dehiscence (1%), scrotal hematoma requiring drainage (< 1%), erectile dysfunction (< 1%), wound infection (< 1%), and fistula formation (< 1%).²⁴

Perineal Urethrostomy

Perineal urethrostomy (PU) is indicated in patients who are unfit for urethroplasty or may be offered as an alternative to reconstruction in patients with recurrent strictures failing prior reconstruction, preference for seated voiding, buried penis, multiple comorbidities, complex penile strictures (including reoperative hypospadias), lichen sclerosus, poor access to urologic care, and urinary continence status.^28-30 The conventional PU approach can be pursued using transecting or non-transecting techniques and typically involves mobilization of a healthy skin flap, followed by anastomosis to the bulbar urethra proximal to the urethral stricture and distal to the membranous urethra to preserve continence (Figure 8).³⁰

Figure 8: Key steps of the conventional perineal urethrostomy. A) The skin flap is created by a ‘U’ incision, followed by vertical incisions of the bulbocavernosus muscle and membranous urethra. B) Sutures incorporating the urethral mucosal edge, the adventitial edge of the corpus spongiosum, and the perineal skin are placed to preserve the dorsal urethral plate. C) The finished perineal urethrostomy with a Foley catheter placed. Figure adapted from (Myers and McAninch, 2011).³⁰

In studies of patients with complex anterior urethral stricture disease, PU has shown strong success rates of 85-95% and patient-reported satisfaction rates of 97%.^31-33 While short-term complications from PU are rare, urinary tract infections requiring hospital admission, cellulitis, and dehiscence of the inverted U advancement flap have been noted in the immediate postoperative setting.³⁴ In the long-term, postoperative stenosis has been reported in 18% of patients undergoing PU, with a greater incidence in patients with a history of radiation therapy for prostate cancer.³⁴ Of note, preserving the longitudinal blood supply within the bulbar urethra, rather than transecting it, during the creation of the PU reduces the likelihood of postoperative stenosis.³⁴

Management of Urethral Strictures after Genital Gender-Affirming Surgery in Transmasculine Patients

Genital gender-affirming surgery is an important consideration for transgender patients during the transition process. In transmasculine patients, metoidioplasty and phalloplasty are the two standard surgical options. Briefly, metoidioplasty involves the creation of a neophallus from a hormonally enlarged clitoris, which can be performed along with hysterectomy, oophorectomy, vaginectomy, and scrotoplasty with testicular implantation as part of a one-stage surgery.³⁵ In contrast, total phalloplasty is a multi-stage procedure that involves the construction of a neophallus with skin flaps, followed by scrotoplasty and vaginectomy, and possible implantation of the testicles and an erectile device.³⁶ Urethral lengthening is often desired by transmasculine patients who have undergone genital gender-affirming surgery, as this enables patients to void while standing.^35,36 However, urethral lengthening poses key complications of urethral strictures, which can happen in upwards of 60% of patients, and urethral fistulas, which occur in 25-50% of patients.³⁷ Strictures most commonly occur at the proximal and distal anastomoses of the fixed urethra to the native urethra and the penile urethra, respectively (Figure 9).³⁷ In patients with short urethral strictures, the Heineke-Mikulicz procedure, which allows for enlargement of the urethral diameter without excision of the stricture, led to the highest success rate.³⁸ In patients with longer, more complex strictures, substitution urethroplasty with a buccal graft has been shown to be efficacious.³⁸

Figure 9: Anatomy of the urogenital tract after genital gender-affirming surgery with urethral lengthening, as represented by the “fixed urethra” segment. Urethral strictures most commonly occur at the proximal and distal urethral anastomoses. Figure adapted from (Veerman et al., 2020).³⁷

Management of Urethral Injuries Caused by Pelvic Fractures

Urethral injuries can occur in up to 25% of patients presenting with pelvic fractures and are thought to be caused by an avulsion of the membranous urethra from the bulbar urethra at their junction point at the perineal membrane.³⁹ The 2023 AUA guidelines recommend the use of RUG and VCUG for preoperative planning after pelvic fracture urethral injury.³ Major trauma-induced injuries should be controlled first and, once the patient is stabilized, the urethral repair should be planned. Management includes initial placement of a suprapubic tube, or endoscopic realignment in select patients, followed by urethroplasty with anastomotic reconstruction through a perineal approach.³

Postoperative Care

Following endoscopic urethral dilation or DVIU, the catheter may be safely removed after 24-72 hours, as prolonged catheter placement has not been shown to be beneficial.³ Patients undergoing urethroplasty may be discharged on the same day or one day after surgery, and postoperative pain can typically be managed with non-opioid pain medication.⁴⁰ Catheters are usually in place for 1-4 weeks after urethroplasty, although recent studies show that earlier removal (3-21 days post-urethroplasty) does not increase the rate of urinary extravasation or stricture recurrence during long-term follow-up.⁴¹ Patients undergoing perineal urethrostomy are commonly discharged on the same day as the surgery, and the catheter is left in place for 2-10 days.³¹ Importantly, patients should be monitored for stricture recurrence after surgical intervention based on patient-reported voiding symptoms, uroflowmetry, post-void residual, and/or routine evaluation with urethrocystoscopy, urethral ultrasound, and/or RUG.³

Summary

A urethral stricture is an abnormal narrowing within the urethral lumen that is caused by fibrosis or scarring of the mucosa, often as a result of idiopathic, iatrogenic, or traumatic causes. In addition to obstructive voiding symptoms experienced by the patient, retrograde urethrograms and/or voiding cystourethrograms can formally diagnose urethral strictures. Urethral strictures warrant prompt intervention with endoscopic approaches, urethroplasty, or perineal urethrostomy to prevent significant, potentially life-threatening complications.

References

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AUTHORS

2023 Version

Nityam Rathi
Cleveland, OH
Disclosures: Nothing to disclose

Dr. Paul H. Chung, MD
Philadelphia, PA
Disclosures: Nothing to disclose

Dr. Alex J. Vanni, MD
Burlington, MA
Disclosures: Nothing to disclose

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