1. Introduction

Urethral stricture is a debilitating condition that predominantly affects males across all age groups, with a higher incidence in those above 55 years of age.¹  It significantly impairs quality of life and imposes a substantial economic burden on both the healthcare system and patients. Globally, the prevalence of urethral stricture is estimated to range from 0.6% to 1.4%,¹ corresponding to 229–627 cases per 100,000 males¹. The etiology of urethral strictures can be broadly classified into four major categories: idiopathic, iatrogenic, inflammatory, and traumatic. Among these, idiopathic and iatrogenic causes are the most common, each contributing approximately 33% of cases. Traumatic causes account for about 19%, while inflammatory causes account for roughly 15%. Additionally, infectious etiologies may account for up to 26.6% of patients, and these strictures are typically long-segment (>4 cm). The etiology varies by geographical region, with developing nations more often seeing it as an infectious pathology.¹ Patients with urethral stricture commonly experience problems such as detrusor hypertrophy, bladder diverticula, recurrent urinary infections, stone formation, and, in severe cases, renal failure. Common manifestations include a weak or decreased urine stream, reduced urine volume, urinary urgency, painful urination, incontinence, pelvic or lower abdominal pain, urethral discharge, penile swelling, and blood in urine or semen. The urine may also appear dark. This condition significantly impacts both overall health and quality of life². Treatment itself can also lead to adverse outcomes. The most common direct complications following urethral surgery include bleeding, infection, urinary incontinence, erectile dysfunction, and recurrence of the stricture². The exact pathophysiology of the condition remains unclear, but it is often attributed to ischemic spongiofibrosis following infectious, inflammatory, or traumatic injury.² The disease is characterized by excessive fibroblast proliferation, increased collagen production, and extracellular matrix accumulation. Persistent inflammation also plays a crucial role in driving disease progression³. The primary pathological feature of urethral stricture disease is fibrosis of the epithelial-lined corpus spongiosium. As scar tissue forms, the corpus spongiosum contracts, narrowing the urethral lumen. The damaged urothelium becomes less elastic and less able to withstand normal pressure changes during urination. This initiates a vicious cycle in which the stiff, fibrotic tissue sustains further injury from the hydrostatic pressure during voiding, worsening the fibrosis. Spongiofibrosis is aggravated by small tears or fissures in the metaplastic epithelium, allowing urine to seep into the corpus spongiosum. The fibrotic process may progress longitudinally along the urethra or circumferentially into adjacent tissues.³

2. Methodology

2.1. Data search

Although this work does not constitute a formal systematic review, we conducted a structured and targeted literature search to identify relevant clinical studies and reviews reporting maximum urinary flow rate (Qmax) as a postoperative outcome. Electronic searches were performed in PubMed/MEDLINE, Scopus, and Google Scholar, covering articles published between January 2000 and December 2024 to reflect contemporary surgical techniques and evolving endoscopic and reconstructive approaches. The search strategy employed combinations of the following keywords: “Qmax,” “uroflowmetry,” “urethral stricture,” “urethroplasty,” “internal urethrotomy,” “balloon dilatation,” “buccal mucosa graft,” “mucosal preservation,” “functional outcomes,” and “anterior urethral reconstruction.” Reference lists of relevant articles were also manually screened to identify additional eligible studies. Studies were included if they (i) involved adult male patients with urethral stricture disease, (ii) evaluated surgical or endoscopic interventions (including direct vision internal urethrotomy, laser urethrotomy, balloon dilatation, drug-coated balloon (DCB) therapy, buccal mucosa graft urethroplasty, flap-based urethroplasty, excision and primary anastomosis (EPA), or tissue-engineered grafts, and (iii) reported postoperative Qmax, uroflowmetry parameters, or functional voiding outcomes as primary or secondary endpoints. Eligible study designs included randomized controlled trials, prospective and retrospective cohort studies, comparative studies, and relevant systematic reviews or meta-analyses, provided they were published in English and reported at least short-term postoperative follow-up. Studies were excluded if they focused exclusively on pediatric populations, female urethral pathology, or non-clinical models; lacked functional outcome reporting; consisted solely of single-patient case reports or editorials; or provided insufficient follow-up to assess meaningful postoperative functional outcomes. As this review was intended as a structured narrative synthesis rather than a formal systematic review, Preferred Reporting Items for Systematic reviews and Meta-Analyses-guided screening (including a flow diagram), duplicate- and independent-study selection, and a formal risk-of-bias assessment were not performed.

2.2. Categorization of treatment methods based on post-treatment epithelial integrity

The procedures were categorized as those that do not provide immediate postoperative epithelial coverage (e.g., dilatation, urethrotomy—visual internal urethrotomy [VIU]/direct VIU [DVIU]— and balloon dilatation) and those that maintain the integrity of the epithelial lining either by cell therapy or graft-based epithelial/urothelial coverage (e.g., urethroplasty, EPA, and tissue engineering procedures, including the buccal epithelium expanded and encapsulated in a scaffold-hybrid approach to urethral stricture [BEES-HAUS] and minced liquid buccal mucosal grafts [BMGs]). As patient-level data were not available from the included publications, all quantitative analyses were conducted using reported summarized Qmax values. When studies reported Qmax as a range, the midpoint was used to enable graphical and numerical summaries. Qmax values were extracted at baseline and at predefined follow-up time points (immediate postoperative, 1, 3, 6, 9, 12, and >12 months). For each time point and category, we summarized the number of reporting study arms (n), mean, median, and range of Qmax (Table 1). Between-category comparisons at each time point were performed using the Mann–Whitney U test on study-level values (GraphPad Prism). A p-value of < 0.05 was considered statistically significant. These comparisons were considered exploratory and interpreted cautiously, given the heterogeneity in study design, patient selection, stricture characteristics, and outcome reporting.

3. Treatments for urethral stricture

Until about 50 years ago, urethral stricture treatment primarily relied on dilatation and urethrotomy, both of which were blind techniques demanding considerable surgical skill. However, their outcomes were often suboptimal and short-lived.⁴ Today, various treatment options are available, ranging from endoscopic incision to open reconstructive surgery, all aiming to restore a patent urethra and enable normal urination⁴. Despite advancements, dilatation and DVIU remain the most commonly used methods.

Urethral dilatation, whether performed using filiform and followers, urethral sounds, or balloon catheters, works by stretching the scar tissue without tearing the mucosa, thereby gradually widening the lumen. The recurrence rate following dilatation is reported to be around 60% at 48 months⁵. The classical VIU technique, as described by Sachse⁶, involves a single incision at the 12 o’clock position through the stricture. Some surgeons have proposed making multiple radial incisions to improve outcomes, but studies have shown no significant difference between single and multiple cuts.⁵ Following the introduction of optical internal urethrotomy, numerous studies in the 1970s and 1980s reported success rates between 50% and 80%⁵. The best results were observed in short strictures (<1 cm) located in the bulbar urethra with a relatively wide lumen at the time of treatment. Nonetheless, recurrence remains a concern, with DVIU showing a 50% recurrence rate at 48 months^4-6. Patients who fail to respond to repeated DVIU typically have long strictures (>2 cm), penile or membranous involvement, or multiple strictures. Recurrence within three months of DVIU is associated with a stricture-free rate of only 30% at two years and 0% at four years, whereas patients undergoing three or more DVIUs experience complete failure (100%).^4-7 To enhance DVIU outcomes, several adjunctive strategies have been explored. The use of intermittent catheterization (IC) remains controversial; although it may delay recurrence, it requires ongoing urethral manipulation and may worsen fibrosis⁷. Additionally, IC increases the risk of urinary tract infection, bleeding, and other complications. Various injection therapies have also been tested to improve DVIU success rates. Mitomycin C, an antifibrotic agent, has produced mixed results: some studies report excellent outcomes in recurrent strictures, while others show only modest benefit.⁷ Triamcinolone injection administered during DVIU has demonstrated good efficacy, reducing recurrence rates from 50% to 21%⁷.

Urethroplasty is considered the definitive surgical treatment for urethral stricture, achieving success rates of 85–90% in simple cases and 80% or higher in complex reconstructions.^4-7 Evidence indicates that, compared to urethral dilatation or DVIU, open urethroplasty offers the highest likelihood of long-term cure.^4-7 Both anastomotic and substitution graft urethroplasty demonstrate excellent long-term outcomes, though their postoperative effects differ. EPA involves removing the fibrotic segment of the urethra and directly reconnecting the healthy ends. EPA is considered the preferred treatment for short bulbar urethral strictures of traumatic or iatrogenic etiology, regardless of cause or previous therapy. This technique is typically applied to strictures ≤2 cm in length. A long-term success rate of >90% has been reported with EPA⁸. Substitution graft urethroplasty is widely performed as a definitive solution for both short and long (>2 cm) strictures. The surgical exposure is similar to that used in EPA, but instead of removing the fibrotic segment, a graft is sutured alongside the opened strictured segment of the urethra to enlarge the lumen. The graft receives structural support and blood supply from the corpora cavernosa (when placed dorsally), the corpus spongiosum (when ventral), or the dorsal spongiosal layer (when used as an inlay, as in the Snodgraft or Asopa techniques)⁸. Early reconstructive procedures primarily involved local skin flaps from the penis or scrotum, which showed failure rates of about 20–30%.⁹ To achieve more durable results, surgeons began exploring free graft substitutions, such as meshed split-thickness skin grafts, which achieved around 80% success, though they required multiple stages and carried donor-site morbidity.⁹ Bladder mucosa grafts were another option, with about 12% failure at 28 months,⁹ but harvesting them through open surgery added further complications. The first use of BMGs for urethral reconstruction was reported in the early 19^th century by Sapezhko¹⁰, who recognized buccal mucosa as an ideal graft due to its thick epithelium, resistance to infection, and ease of harvest. Interestingly, oral mucosal grafts (OMGs) predated both split-thickness skin grafts and bladder mucosa grafts but eventually fell out of favor⁹. The technique was revived in 1941 when Humby¹⁰ successfully used BMGs for urethral reconstruction. Modern refinements began in 1996, when Morey and McAninch¹⁰ introduced a two-team ventral onlay approach using BMGs, followed by Barbagli et al.¹¹, who popularized the dorsal onlay technique for bulbar strictures. Later, in 2009, Kulkarni et al.¹¹ described a unilateral dorsal onlay modification, further enhancing surgical precision and outcomes. Recurrence rates following BMG urethroplasty vary depending on the site, length, and cause of the urethral stricture. A systematic review involving over 2,000 BMG urethroplasties found comparable success rates among different surgical approaches—dorsal onlay (88.4% at 42.2 months), ventral onlay (88.8% at 34.4 months), lateral onlay (83% at 77 months), Asopa technique (86.7% at 28.9 months), and Palminteri technique (90.1% at 21.9 months), indicating that outcomes are largely similar across these methods¹¹.

Tissue-engineered urethroplasty represents the most recent advancement in urethral reconstruction. Although OMGs remain the gold standard, their use is not always feasible. Limitations include patient refusal of oral graft harvest, patients with a congenitally small oral cavity (e.g., in some Asian populations), patients with restricted mouth opening due to prior trauma or mandibular surgery, patients who need bilateral or large rectangular grafts in staged repairs, and those with recurrent strictures who have exhausted both buccal graft sites¹¹. Researchers have investigated the regenerative potential of urethral and oral mucosal cells in vitro, demonstrating that both tissues exhibit high proliferative capacity and maintain normal morphology, genetic stability, and growth factor dependence.¹² In 2008, Bhargava et al.¹³ reported the first use of tissue-engineered (TE) autologous oral mucosa grafts for urethral reconstruction in five patients with lichen sclerosus-related strictures. In 2011, the authors proposed pre-treating the scaffold with glutaraldehyde and β-aminopropionitrile to minimize graft contraction.¹³ In 2014, Lazzeri et al. ¹⁴ presented preclinical and clinical evaluations of a TE autologous oral mucosa graft product (MukoCell®), focusing on safety. No tumorigenic changes were observed in animal studies. Later, in 2017, the same group conducted a multicenter observational study involving 99 patients with urethral strictures of varied causes and lengths. Reported success rates were 70.8% at 12 months and 76.9% at 24 months, with outcomes depending on surgical expertise (ranging from 0% to 85.7%)¹⁴. In 2018, Barbagli et al.¹⁵ described the technique and long-term results of TE oral mucosa graft implantation in 38 patients. The overall success rate was 84.2%, with 85.7% for ventral onlay, 83.3% for dorsal onlay, 80% for dorsal inlay, and 100% when combined techniques were used¹⁵. The Optilume™ DCB is another recent advancement that integrates mechanical urethral dilatation with localized delivery of paclitaxel, a microtubule inhibitor known for its antifibrotic and antiproliferative effects. The ROBUST I trial, a prospective, multicenter, single-arm study, assessed the outcomes of Optilume™ DCB therapy. At one-year follow-up, the study reported a 70% anatomic success rate without serious adverse events, and results remained consistent at two years¹⁶. Vaddi et al.¹⁷ introduced an innovative endoscopic tissue engineering technique, the BEES-HAUS. In their study, which used a hybrid cell therapy comprising in vitro-cultured autologous buccal epithelial cells and endotoxin-free Festigel scaffold, they reported that four out of six patients achieved a recurrence-free interval at a three-year follow-up, demonstrating the long-term effectiveness of this minimally invasive procedure¹⁷. Additionally, researchers have demonstrated that the engraftment of transplanted buccal epithelial cells prevented exposure of sub-urothelial tissue to urine^18,19, and was therefore considered to reduce the recurrence of urethral stricture. Li et al.²⁰ described a simpler, single-step approach in which minced buccal mucosal tissue mixed with fibrin glue was transplanted into the urethra following DVIU. The technique achieved a functional success rate of 66.7% over 18 months²⁰.

4. Comparison of treatment approaches for urethral stricture

Following a review of the treatment options for urethral stricture, we assessed their comparative outcomes. One study provided five different criteria for defining treatment failure after urethroplasty: (i) the need for reintervention, (ii) anatomical recurrence on urethrogram or cystoscopy, (iii) Qmax <15 mL/s, (iv) patient-reported weak urinary stream, and (v) failure by any of the above measures.²¹ The study revealed that success rates varied widely depending on the definition used, indicating a lack of uniformity across studies. This inconsistency limits the ability to make reliable comparisons of outcomes between different treatment techniques²¹.

Building on the comparison of existing urethral stricture treatments, we propose that postoperative Qmax measured by uroflowmetry can serve as a strong predictor of long-term treatment success²⁰. Uroflowmetry is a simple, noninvasive assessment of maximum urinary flow. Uroflowmetry involves a well-hydrated patient voiding into a uroflowmeter, which in turn generates a “flow curve”²². The interpretation of uroflowmetry results helps differentiate normal urinary patterns from benign prostatic obstruction and urethral strictures. A Qmax below 12 mL/s typically suggests the presence of a lower urinary tract obstruction or urethral narrowing.²² Additionally, the shape of the flow curve offers diagnostic clues wherein urethral strictures often produce a sharp, flat-topped plateau at the peak flow level. For accuracy and reproducibility, the test should ideally be performed with a voided urine volume exceeding 150 mL^1,23.

4.1. Maximum urinary flow rate reported for different urethral stricture treatments

In the study by Vyas et al.²⁴, urethral dilatation resulted in an initial increase in Qmax from 5.7 mL/s to 19.1 mL/s at one month, which subsequently declined to 14.3 mL/s at three months and 12.7 mL/s at six months, indicating a gradual reduction in Qmax over time. A systematic review on balloon dilatation reported that the preoperative Qmax ranged from 5 to 7.6 mL/s, which improved to 14.3–22.2 mL/s at three months, but subsequently declined to 12.7–19.8 mL/s at six months²⁵. Akkoc et al.²⁶ reported that use of an Amplatz renal dilator for treatment of urethral strictures resulted in a preoperative mean Qmax of 7.0 mL/s (range: 4–12), improving to 18.0 mL/s (range: 15–22; p<0.001) at one month, decreasing to 17.0 mL/s (range: 13–21; p<0.001) at six months, and 15.0 mL/s (range: 12–17; p<0.001) at 12 months. In a study by Tinaut-Ranera et al.²⁷, patients who underwent urethrotomy showed an increase in Qmax from 5.1 ± 1.9 mL/s to 13.5 ± 8.1 mL/s  mL/s at six months. In the same study, those treated with urethroplasty demonstrated an improvement from 6.4 ± 2.1 to 14.7 ± 8.8 mL/s, while patients who underwent a combination procedure exhibited a rise from 4.8 ± 2.4 mL/s to 18.9 ± 10.8 mL/s²⁵. Zheng et al.²⁸ conducted a systematic review comparing cold knife and laser urethrotomy for urethral stricture management. The analysis showed that postoperative Qmax for the cold knife group ranged from 21.4 to 25.86 mL/s at 1–3 days, from 11.92 to 23.4 mL/s at three months, from 11.8 to 21.9 mL/s at six months, and from 9.8 to 13.7 mL/s at 12 months. For the laser group, Qmax ranged from 21.7 to 27.54 mL/s at 1–3 days, from 11.44 to 23.6 mL/s at three months, from 10.72 to 23.8 mL/s at six months, and from 10.6 to 13 mL/s at 12 months²⁸. Azab et al.²⁹ reported that patients treated with the Amplatz dilator showed a mean preoperative Qmax of 8.31 mL/s, which increased to 26.39 mL/s at 15 days, 21.33 mL/s at six months, and 18.06 mL/s at 12 months. In comparison, those who underwent cold knife incision demonstrated mean Qmax values of 7.73 mL/s preoperatively, increasing to 25.96 mL/s at 15 days, 22.8 mL/s at six months, and 21.9 mL/s at 12 months²⁹.

Chi et al.³⁰ conducted a comparative evaluation of two treatment modalities: holmium: yttrium aluminum garnet laser internal urethrotomy and cold knife optical internal urethrotomy. Their analysis demonstrated that postoperative Qmax for the holmium: yttrium aluminum garnet laser internal urethrotomy group was 18.88–21.33 mL/s at one month and 18.91–23.6 mL/s at three months, while for the cold knife optical internal urethrotomy group, the corresponding Qmax values ranged between 18.71–22.99 mL/s at one month and 17.0–23.4 mL/s at three months³⁰. Noureldin et al.³¹ investigated intralesional injection of mitomycin C using a novel adjustable-tip needle after VIU. According to their findings, the preoperative Qmax was 9.0 ± 1.73 mL/s in Group A (VIU with mitomycin C injections) and 8.42 ± 1.35 mL/s in Group B (VIU alone). At three months postoperatively, Qmax improved to 17.95 ± 3.38 mL/s in Group A but deteriorated to 4.20 ± 3.87 mL/s in Group B. At six months, the values improved to 17.29 ± 3.42 mL/s and 13.76 ± 3.99 mL/s, respectively, while at nine months, Qmax was 17.43 ± 3.26 mL/s in Group A and 13.63 ± 3.49 mL/s in Group B³¹.

The ROBUST III randomized trial evaluated the safety and efficacy of Optilume™ DCB compared with standard endoscopic management for recurrent anterior urethral stricture in men. In the intervention arm, mean Qmax improved from 7.6 mL/s at baseline to 15.5 mL/s at one year, which decreased to 10.6 mL/s at three years³². Babaley et al.³³ compared postoperative outcomes between DVIU and urethroplasty. They reported that preoperative Qmax was 8.3 ± 3.1 mL/s for the DVIU group and 7.9 ± 4.05 mL/s for the urethroplasty group. At three months, Qmax improved to 21.2 ± 3.76 mL/s and 26 ± 2.9 mL/s, respectively. At six months, Qmax values were 20 ± 3.5 mL/s for DVIU and 23.4 ± 2.5 mL/s for urethroplasty. These findings demonstrated that urethroplasty provided a greater and more sustained improvement in Qmax, indicating better longer-term functional outcomes compared with DVIU³³.

For EPA, an improvement from a mean preoperative Qmax of 8.43 mL/s to a three-month postoperative Qmax of 25.09 mL/s, 20.63 mL/s at nine months, and 23.47 mL/s at 12 months has been reported³⁴. Kumar et al.³⁵ compared outcomes of urethroplasty using a BMG versus a preputial skin flap (PSF) for urethral stricture repair. They reported that baseline (preoperative) Qmax was 5.6 ± 0.6 mL/s in the BMG group and 6.5 ± 0.6 mL/s in the PSF group. At six months postoperatively, Qmax significantly improved to 19.5 ± 1.0 mL/s for the BMG group and 19.1 ± 0.7 mL/s for the PSF group³⁵. Tyagi et al.³⁶ compared augmentation urethroplasty using BMGs and penile skin grafts (IPG) for the management of anterior urethral stricture disease. In their study, preoperative Qmax was 8.10 ± 1.61 mL/s in the BMG group and 7.91 ± 1.35 mL/s in the IPG group. At three months, Qmax improved to 25.50 ± 4.40 mL/s for BMG and 25.15 ± 4.52 mL/s for IPG. At six months, values were 23.95 ± 5.61 mL/s (BMG) and 23.44 ± 3.40 mL/s (IPG). At 12 months, Qmax remained stable at 23.96 ± 4.83 mL/s for BMG and 22.10 ± 5.19 mL/s for IPG. At 18 months, Qmax was 23.93 ± 3.83 mL/s for BMG and 21.00 ± 5.00 mL/s for IPG, with a mean increase from baseline of 14.7 ± 2.7 mL/s and 13.3 ± 3.3 mL/s, respectively³⁶.

In the study on the use of tissue-engineered autologous oral mucosa graft (MukoCell) for urethral reconstruction, the preoperative mean Qmax was 8.3 ± 4.7 mL/s, which improved significantly to 25.4 ± 14.7 mL/s postoperatively³⁷. In a comparative study evaluating MukoCell® versus native oral mucosa graft for urethral reconstruction, postoperative Qmax was reported as 18.9 mL/s (interquartile range: 15.3–25.4) in the MukoCell® group and 20.6 mL/s in the native oral mucosa graft group at nearly one-year follow-up³⁸. In the BEES-HAUS procedure, baseline mean Qmax was 6 mL/s, which improved to 24 mL/s postoperatively, with 66.6% of patients maintaining a Qmax greater than 20 mL/s at a three-year follow-up¹⁷. In the study on endoscopic liquid BMG urethroplasty, the mean follow-up period was 18 months, during which patients demonstrated improvement in Qmax from 7.2 cc/s preoperatively to 20.2 cc/s²⁰.

4.2. Advantages and disadvantages of each treatment approach

When comparing treatment strategies, minimally invasive options (dilatation, DVIU, and laser urethrotomy) are attractive due to lower upfront morbidity, short operative time, and broad availability, making them practical for short, non-obliterative strictures; however, their disadvantages include higher recurrence rates, potential cumulative epithelial injury with repeated procedures, and a tendency for Qmax to decline over time as spongiofibrosis progresses³⁹. DCBs may provide an intermediate option by combining mechanical dilatation with antiproliferative drug delivery, potentially improving durability in selected recurrent strictures; disadvantages include device cost, limited long-term data in some subgroups, and restricted applicability for long, complex, or obliterative strictures^40-42. Open urethroplasty (EPA for short strictures; substitution graft or flap urethroplasty for longer segments) offers the key advantage of higher long-term cure rates and more sustained functional improvement, and in epithelial coverage approaches, restoration of a mucosal barrier may reduce urine-driven inflammation, and fibrotic remodeling; disadvantages include greater surgical complexity, longer recovery, the need for specialized expertise, and procedure-specific risks (e.g., donor-site morbidity for oral graft harvest and learning curve effects)^11,42. Therefore, treatment selection should be individualized based on stricture length, location, etiology, prior interventions, tissue quality, and local reconstructive expertise.

4.3. Comparative outcomes based on post-treatment epithelial integrity

Baseline Qmax was similar between procedures categorized as compromising epithelial integrity and those maintaining epithelial integrity (p = 0.85). At follow-up, procedures maintaining epithelial integrity demonstrated consistently higher study-level Qmax values, with the largest separation observed at three months (p = 0.009) and persisting through six months (p = 0.02). Although the differences at 12 months (p = 0.09) and three years (p = 0.33) did not reach statistical significance, the epithelial coverage group maintained higher Qmax values, suggesting sustained clinical benefit. Although fewer studies reported beyond 12 months, the epithelial maintenance category continued to demonstrate higher Qmax values at ≥18–36 months, though statistical significance was not reached due to limited reporting and heterogeneity. Figures 1 and 2 illustrate mean Qmax trajectories at each time point (Figure 1) and over time (Figure 2) by category (maintain vs compromise epithelial integrity). Table 2 summarizes the Qmax values reported across studies at different time points, categorized by the presence or absence of immediate postoperative epithelial coverage.

Figure 1. Bar chart showing mean maximum urinary flow rate (Qmax) values at predefined follow-up intervals, comparing procedures that compromise epithelial integrity versus those that maintain epithelial integrity.

Procedures maintaining epithelial integrity demonstrated consistently higher study-level Qmax values, with the largest separation at three months (p = 0.009) and a persistent difference at six months (p = 0.02). Differences were not statistically significant at 12 months (p = 0.09) and three years (p = 0.33), though higher Qmax values were still observed in the epithelial integrity maintenance group.

Note: * represents statistical significance; ns: not significant.

Figure 2. Mean maximum urinary flow rate (Qmax) trajectory over time by treatment category.

Qmax values were extracted from included studies and summarized by follow-up time point; when ranges were reported, midpoint values were used for visualization. Procedures maintaining epithelial integrity showed higher mean Qmax values, with the clearest separation at three months (p = 0.009) and sustained at six months (p = 0.02). The difference narrowed and did not reach statistical significance at 12 months (p = 0.09) and three years (p = 0.33), but the epithelial integrity maintenance group continued to show numerically higher Qmax values.

5. Discussion

The cumulative analysis of clinical data from the included interventional approaches suggests that Qmax serves as a reliable functional biomarker for assessing the success of urethral stricture management. Postoperative trends consistently show that higher immediate postoperative Qmax values correlated with long-term patency and fewer recurrences, whereas a gradual decline over follow-up reflected progressive fibrosis or subclinical restenosis. Early postoperative Qmax, therefore, not only signifies technical success but also reflects the ongoing biological healing response within the reconstructed urethra. Procedures such as BMG urethroplasty and tissue-engineered graft-based reconstructions provide immediate epithelial coverage over the denuded urethral surface. This coverage, we hypothesize, prevents urine-induced inflammation of the subepithelial tissues, a major contributor to stricture recurrence⁴⁵. Accordingly, epithelial grafts may act as a biological shield, minimizing urine infiltration, promoting organized epithelial regeneration, and thereby reducing the risk of recurrent fibrosis^17,46. Unlike simple mechanical procedures such as urethrotomy or dilatation, which can reinjure the scarred segment and exacerbate fibrosis, graft-based techniques may support a more regulated wound healing pathway. The improvement in Qmax following BMG urethroplasty or cell-based therapies reflects successful graft integration and mucosal regeneration. Serial uroflowmetry thus provides a noninvasive dynamic correlate of healing, making it a practical early predictor of recurrence before failure becomes apparent on imaging or cystoscopy.

Mechanistically, Qmax values can be interpreted as a functional marker of the balance between epithelial regeneration and spongiofibrotic remodeling. When reconstructive procedures achieve early, continuous epithelial coverage, they limit urine permeation into subepithelial tissue and reduce the inflammatory cascade that drives fibroblast activation and collagen deposition. Conversely, incomplete or delayed epithelial restoration sustains local irritation and cytokine signaling, favoring progressive extracellular matrix accumulation and contracture, clinically manifesting as a gradual decline in Qmax over follow-up. This inference is supported indirectly by reports on antifibrotic interventions: for example, tamoxifen’s antifibrotic activity has been linked to downregulation of transforming growth factor beta signaling and collagen metabolism (reduced collagen I/III, fibronectin, and transforming growth factor beta 1 expression; inhibition of fibroblast proliferation) in renal fibrosis models.⁴⁷ Clinically, a randomized trial reported that patients receiving tamoxifen after internal optical urethrotomy had lower symptom scores and higher Qmax than controls⁴⁷. Taken together, these data reinforce the biological plausibility that interventions that attenuate profibrotic signaling can preserve lumen caliber and sustain urinary flow. In the same context, our subgroup trends (Table 2) further support the notion that procedures that maintain epithelial integrity and vascular supply are more likely to sustain higher Qmax over time. Techniques designed to minimize ischemia (e.g., limited urethral mobilization, non-transecting principles, and onlay approaches that preserve neurovascular inputs) plausibly improve graft integration, support epithelial continuity, and reduce the inflammatory milieu that precedes fibrosis^48,49. Therefore, the observed differences in Qmax between procedures that “maintain” epithelial integrity and those that “compromise” it can be interpreted not only as a functional outcome but also as an indirect readout of wound-healing quality. Vaddi et al.¹⁷’s BEES-HAUS technique in a subsequently published report⁵⁰ provided mechanistic insights into the urethral healing process. In that follow-up study, they reported that both two-dimensional cultured and three-dimensional Festigel cultured buccal epithelial cells contributed to clinical improvement, reflected by increased uroflowmetry-derived Qmax and reduced urethral stricture recurrence. These benefits were attributed to restoration of epithelial coverage through engraftment of the transplanted three-dimensional epithelial cells, along with paracrine effects, including insulin growth factor 1-mediated signaling, which may support epithelial regeneration and attenuate fibrotic remodeling⁵⁰.

Our findings also align with large-scale endoscopic datasets that have employed DCB technology, where improvements in Qmax accompany durable symptom relief over follow-up, consistent with a model in which suppression of restenosis pathways (alongside mechanical dilatation) helps stabilize flow. For example, published Optilume trials report sustained improvement in objective voiding parameters, including Qmax, across follow-up intervals, supporting the broader concept that modulating the post-intervention healing response is central to maintaining patency^51,52. A nationwide internet-based survey of Chinese urologists⁵³ indicated that urethral dilatation and internal urethrotomy remain dominant first-line approaches, and that many clinicians employ a “reconstructive ladder” strategy in which urethroplasty is performed predominantly after minimally invasive failure. This has implications for recurrence biology and Qmax trajectories, as repeated instrumentation may perpetuate inflammation and fibrosis in a subset of patients⁵³. In parallel, high-volume reconstructive centers have reported strong outcomes with definitive reconstruction for complex diseases. Notably, one group described a progressive transperineal anastomotic urethroplasty strategy for pelvic fracture urethral distraction defect in a cohort, achieving a high overall success rate and providing a model for procedural standardization and training⁵⁴. More recently, the same group reported urethral suspension-assisted urethral anastomosis for complex long-segment posterior strictures, with most patients maintaining unobstructed voiding and a high postoperative Qmax at follow-up⁵⁵. Collectively, these reports support the concept that definitive reconstruction, when technically feasible and performed in experienced hands, can achieve durable functional patency, which should translate into sustained improvements in Qmax over time.

Clinically, Qmax thresholds are best interpreted as ranges rather than as a single fixed cutoff. A Qmax value >15 mL/s is generally considered reassuring and is commonly used in follow-up algorithms to reduce the need for invasive testing when symptoms are well controlled. Values between 10 and 15 mL/s may be variably symptomatic and can represent mild or compensated obstruction, whereas Qmax values below 10–12 mL/s more strongly suggest clinically significant obstruction and warrant closer clinical evaluation.^1,23,42 In the present analysis, both the magnitude and durability of postoperative Qmax, particularly the achievement and maintenance of values at or above approximately 15 mL/s, appear to serve as pragmatic indicators of functional success. Conversely, a progressive decline into the <10–12 mL/s range may function as an early warning sign of recurrent narrowing, even before anatomical failure becomes evident on cystoscopy or imaging^1,23,42. Furthermore, beyond urethral stricture disease, procedures demonstrating sustained high postoperative Qmax values may be suitable for adaptation in hypospadias cases, which often develop urethral stricture as a postoperative complication⁵⁶.

One of the limitations of our analysis is that it is a structured narrative synthesis and does not constitute a formal systematic review or meta-analysis. A systematic review would be essential to determine whether a higher postoperative Qmax serves as an indicator of procedural success. Patient-level data were not available from the included studies; therefore, multivariable confounding adjustment, survival analyses (Kaplan–Meier), assessment of attrition bias, and power calculations could not be performed. The study-level quantitative comparisons presented here are exploratory and may be influenced by heterogeneity in study design, stricture characteristics, follow-up duration, and reporting practices. Future work using patient-level pooled datasets or formal meta-analysis with standardized endpoints is warranted. Another limitation of this narrative review approach is that we did not include a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram or perform a formal risk-of-bias assessment using standardized tools; therefore, the reproducibility of study selection and the completeness of study capture may be reduced, and the findings should be interpreted cautiously in view of potential selection and reporting biases.

An additional challenge in comparing Qmax outcomes across treatment modalities was the lack of standardized, quantitative preoperative stricture characterization across studies. This point has been specifically emphasized by a group of investigators who developed the U.L.T.R.A. measurement rating system using urethral ultrasonography/contrast ultrasound to enable reproducible phenotyping and refined grading of anterior urethral strictures. The U.L.T.R.A. system incorporates five objective anatomical indicators: (U) stricture site, (L) length, (T) scar thickness, (R) stricture-to-proximal urethral dilatation diameter ratio (within 10 mm proximally), and (A) single versus multiple strictures (with an “l” suffix for lichen sclerosus), to better stratify disease severity and guide individualized treatment selection⁵⁷. By enabling more consistent reporting of stricture morphology and complexity, such standardized scoring frameworks could improve cross-study comparability and help interpret postoperative Qmax trajectories more accurately.

Since Qmax is a noninvasive test, we only included studies that reported Qmax as a primary outcome. Invasive tests such as cystoscopy and retrograde urethrogram may induce inflammation in the strictured segment, which requires healing post-procedure. Therefore, we relied on Qmax measured by uroflowmetry as a safer and more consistent outcome parameter. With regard to BMG urethroplasty, given that its outcome depends heavily on surgical expertise¹, variations arising from the learning curve must be taken into account when evaluating long-term post-intervention outcomes. In the case of cell-based therapies, standardization of cell dosage has not yet been established, as there is no precise method to determine the exact suburothelial area exposed by urethrotomy that requires cellular engraftment. This limitation arises because the urothelium is folded into rugae that unfold only during voiding, making accurate estimation difficult.

6. Conclusion

In summary, Qmax is an effective predictive marker of reconstructive success after urethral stricture, leading us to recommend that immediate postoperative Qmax be used as a benchmark to predict the outcome of therapeutic urethral stricture treatment. Procedures that restore immediate epithelial coverage, such as BMG urethroplasty, tissue-engineered mucosal grafts, or hybrid scaffold-assisted approaches (e.g., BEES-HAUS and minced grafts), showed not only higher immediate postoperative Qmax values but also sustained long-term improvement. A recently reported simplified version of BEES-HAUS called buccal epithelium hashed and encapsulated in scaffold-hybrid approach to urethral stricture (BHES-HAUS)⁵⁸, which was not included in this comparative evaluation as only preliminary outcomes are currently available (Qmax = 29.8 ± 7.3 mL/s in 2 months)^59,60 may, given its potential to provide immediate epithelial coverage, be considered among procedures that preserve epithelial integrity after further validation, potentially leading to improved outcomes in the future.

In patients with urethral stricture following intervention, serial uroflowmetry with Qmax assessment during follow-up provides a practical, noninvasive method for monitoring functional patency. In this review, we categorized and compared outcomes across interventions based on whether epithelial integrity was maintained, using Qmax as the primary outcome indicator. To our knowledge, this is the first report to adopt such an approach. Among the interventions, EPA, BMG-plasty, and cell-based therapies, such as BEES-HAUS, minced grafts, and the BHES-HAUS concept, maintain epithelial integrity, thereby preventing exposure of the suburothelium to urine-triggered inflammation and, consequently, the recurrence of stricture. While this framework supports prioritizing integrity-preserving approaches over procedures such as DVIU or balloon dilatation, which disrupt the urothelium, treatment selection should also consider procedural complexity and resource availability. Accordingly, a stepwise treatment ladder may be proposed, favoring BHES-HAUS or minced grafts, followed by BEES-HAUS, and subsequently by EPA or BMG urethroplasty, in ascending order of procedural complexity and expertise required.