Effect of Urodynamic Bladder Outlet Obstruction on Bladder Trabeculation Grade in Patients With Benign Prostatic Hyperplasia: Retrospective Patient Cohort Study
Article information
Abstract
Purpose
This study aimed to evaluate the correlation between bladder outlet obstruction (BOO) and bladder trabeculation in patients with benign prostatic hyperplasia (BPH).
Methods
We analyzed data from consecutive BPH patients from July 2014 to June 2024, who underwent urodynamic study (UDS) and cystourethroscopy. The results of free uroflowmetry, filling cystometry, and pressure-flow study were analyzed to evaluate functional parameters. For anatomical parameters, bladder trabeculation grade, lateral lobe protrusion of prostate, and bladder neck elevation (BNE) measured in cystourethroscopy were used. BOO was defined as the BOO index of 40 or higher in UDS. Bladder trabeculation was graded using our previous studies.
Results
Among total of 1,452 BPH patients, 1,028 patients had trabeculation on cystoscopy. Age, serum prostate-specific antigen, postvoid residual, total prostate volume, transition zone volume, terminal type detrusor overactivity, detrusor pressure at the maximal flow rate, bladder contractility index (BCI), and BOO index increased according to increase in bladder trabeculation. Multivariable logistic analysis showed that bladder trabeculation was significantly associated with age (odds ratio [OR], 1.05; P<0.001), kissing sign (OR, 1.55; P=0.007), BNE (OR, 1.76; P<0.001), detrusor overactivity (OR, 1.88; P=0.002), BCI (OR, 1.01; P=0.037), BOO (OR, 2.27; P<0.001). BOO had the greatest correlation with bladder trabeculation. In addition, BOO index showed a positive correlation (r=0.39, P<0.001) with bladder trabeculation. BOO index well distinguished between moderate trabeculation of grade 2 or higher in receiver operating characteristic analysis (area under curve=0.72, P<0.001).
Conclusions
Our results showed that the severity of BOO is positively associated with the severity of bladder trabeculation.
INTRODUCTION
Benign prostatic hyperplasia (BPH) is a highly prevalent condition affecting men over 50 years of age, with its incidence increasing dramatically in accordance with population aging [1]. As BPH progresses, the prostate is known to increase in size, causing bladder outlet obstruction (BOO) [2].
Functional and morphological changes in the bladder are observed in a substantial proportion of BPH patients [3]. Among these, morphological changes in the bladder are known to be a result of fibrotic remodeling of the detrusor muscle, as shown in previous animal experiments [4]. This process leads to the presence of irregular intraluminal contours within the bladder, called trabeculation [5]. Severe bladder trabeculation is associated with functional deterioration, including significant increases in postvoid residual volume (PVR), reductions in maximum flow rate (Qmax), and elevated rates of detrusor instability [6, 7].
El Din et al. [7], in a study of 492 elderly men presenting with lower urinary tract symptom (LUTS), demonstrated that a correlation was found between bladder trabeculation and grade of BOO. However, El Din did not employ objective criteria for evaluating bladder trabeculation grade and did not exclude conditions such as neurogenic bladder that affect functional and morphological changes on the bladder. In our previous studies, we established a grading system for bladder trabeculation based on cystourethroscopy [8] and radiologic imaging [9] of patients with neurogenic bladder. Nevertheless, large-scale study elucidating the relationship between trabeculation grade and BOO in BPH patients has been lacking.
Therefore, we aimed to evaluate the correlation between the severity of BOO and bladder trabeculation grade in patients with BPH.
MATERIALS AND METHODS
Study Subjects
Our study included BPH patients aged 50 years or older who underwent urodynamic study (UDS) at Seoul National University Hospital (SNUH) consecutively between July 2014 and June 2024. The study protocol was approved by the SNUH Institutional Review Board (IRB No. 2411-086-1587). Among these subjects, 1,452 patients who underwent cystourethroscopy were extracted and their data were analyzed. Exclusion criteria were neurogenic bladder accompanied by neurological disorders that significantly affected LUTS, history of surgical intervention or radiotherapy for malignancy within the pelvic cavity, prior BPH surgery, urethral stricture, pelvic fracture history, and congenital genitourinary anomalies. However, patients with minor neurological conditions judged not to affect LUTS, such as mild cognitive impairment or herniated intervertebral disc without neurological symptoms, were included in the analysis.
Study Design
Our study was a retrospective observational study based on electronic medical records. Patients who visited SNUH urology outpatient clinic during the study period and received clinical evaluation by 2 urologists (SJO or SYC) underwent comprehensive history taking to assess age and underlying diseases including hypertension, diabetes, cardiovascular disease, and neurological disorders, followed by physical examination including digital rectal examination. International Prostate Symptom Score questionnaire scores were obtained, and urinalysis and prostate-specific antigen (PSA) were checked. Uroflowmetry and bladder scan for PVR assessment were conducted. Transrectal ultrasound was performed to measure total prostate volume and transition zone volume. If necessary, patients with palpable nodules or elevated PSA underwent multiparametric magnetic resonance imaging and biopsy for prostate cancer screening.
UDS was performed in all patients using the same protocol with a multichannel urodynamic machine (UD-2000, Solar or Nexam Pro, MMS, The Netherlands) [10], and results were interpreted according to International Continence Society standardization [11, 12]. Cystourethroscopy was performed in the dorsal lithotomy position using a 17F 30° rigid endoscope (Karl Storz, Germany) [8]. Following application of topical lidocaine jelly to the urethra, the endoscope was inserted and positioned at the verumontanum to evaluate the entire urethra including the prostatic urethra and bladder neck. After checking maximal voided volume from the voiding diary before cystourethroscopy, bladder filling was performed with normal saline to 70%– 80% of this volume for bladder inspection. Bladder evaluation included ureteral orifice location, mucosal abnormalities, and trabeculation grading. Cystoscopic findings were described by a single urologist (SJO) during cystoscopy in a blinded manner. Digital images of the bladder including the trigone, dome, and posterior wall were acquired using a digital recorder (Telecam SL II; Karl Storz).
Study Parameters
Maximal cystometric capacity, bladder compliance, detrusor activity, and bladder sensation were extracted from filling cystometry, and Qmax and detrusor pressure at maximal flow rate (PdetQmax) were checked from pressure-flow study. BOO index was calculated as PdetQmax–2×Qmax, and urodynamic BOO was defined as a BOO index of 40 or greater [13]. Bladder contractility index (BCI) was calculated as PdetQmax+5× Qmax, and BCI below 100 was considered as reduced contractility [14]. For patients who underwent video UDS, fluoroscopic findings were additionally investigated.
Cystourethroscopic parameters included lateral lobe protrusion of prostate, degree of bladder neck elevation [15], and bladder trabeculation grade [8, 9]. Bladder trabeculation was graded from 0 to 3 according to a previously established classification system (Fig. 1), which has demonstrated almost perfect interobserver and test–retest reliability in an independent cohort [8]. Based on the degree and extent of trabeculation, the grades were defined as follows: grade 0 (no trabeculation); grade 1 (mild trabeculation with a single layer of muscle bundle formation); grade 2 (moderate trabeculation with 2 layers of muscle bundle less than 50% area of bladder); and grade 3 (severe trabeculation with 2 layers of muscle bundle over 50% area of bladder or more layers of muscle bundle formation).
Representative cystoscopic images demonstrating each trabeculation grade. (A) Grade 0 (no trabeculation). (B) Grade 1 (mild trabeculation with a single layer of muscle bundle formation). (C) Grade 2 (moderate trabeculation with two layers of muscle bundle less than 50% area of bladder). (D) Grade 3 (severe trabeculation with two layers of muscle bundle over 50% area of bladder or more layers of muscle bundle formation).
Statistical Analysis
Statistical data analysis was performed using XLSTAT (Lumivero, USA) software. Continuous variables were analyzed using the Mann-Whitney U-test, and categorical variables were analyzed using the chi-square test. Multivariable logistic regression analysis was performed for identifying factors associated with bladder trabeculation grade. Pearson correlation test was performed for trend analysis. Receiver operating characteristic (ROC) analysis was conducted to determine cutoff values according to trabeculation grade. Statistical significance was established at P-value less than 0.05.
RESULTS
A total of 1,452 subjects were included. The mean age of the study population was 69.3±7.5 years, and the mean BOO index was 40.9±25.8 (Table 1). BOO was present in 602 patients (42.3%), and bladder trabeculation was observed in 1,028 patients (70.8%). Among them, bladder trabeculation grade 1 (mild) was observed in 632 patients (43.5%), grade 2 (moderate) in 241 patients (16.6%), and grade 3 (severe) in 155 patients (10.7%).
Clinical parameters were compared according to the trabeculation grade (Table 2). Age, serum PSA level, PVR, total prostate volume, and transition zone volume increased with higher trabeculation grades (all P<0.001). Among UDS parameters, higher trabeculation grades were associated with increased bladder sensation and terminal-type detrusor overactivity, as well as an increasing trend in PdetQmax on pressure-flow study (all P< 0.001). Conversely, bladder compliance, the proportion of detrusor underactivity, and Qmax on pressure-flow study decreased when trabeculation grade went higher (all P<0.001). Furthermore, BOO index and BCI increased with higher trabeculation grades (all P<0.001). The trends across trabeculation grades were further supported by 95% confidence intervals (CIs) estimated using a bootstrap method (Supplementary Table 1).
The distribution of BOO index according to bladder trabeculation grade was compared with the subgroup analysis according to the presence or absence of BOO, and the trend was assessed using Pearson correlation coefficients (r) (Fig. 2). In the overall patient cohort, BOO index demonstrated a progressive increasing trend with higher trabeculation grade (r=0.39, P<0.001) (Fig. 2A). Among patients with BOO, a similar increasing trend of BOO index according to trabeculation severity was observed (r=0.27, P<0.001) (Fig. 2B). In contrast, among patients without BOO, no significant trend was observed between trabeculation grade and BOO index (r=0.02, P=0.73) (Fig. 2C).
Bladder outlet obstruction (BOO) index (BOOI, mean±standard deviation) according to bladder trabeculation grade with Pearson correlation test. (A) All patients. (B) Patients with BOO. (C) Patients without BOO.
Multivariable logistic regression analysis was performed to evaluate associations between bladder trabeculation and vari-ous clinical factors (Table 3). Significant associations were observed for age (odds ratio [OR], 1.05; 95% CI, 1.03–1.07; P<0.001), kissing sign (OR, 1.55; 95% CI, 1.13–2.14; P=0.007), bladder neck elevation (OR, 1.76; 95% CI, 1.27–2.43; P<0.001), detrusor overactivity (OR, 1.88; 95% CI, 1.27–2.78; P=0.002), BCI (OR, 1.01; 95% CI, 1.00–1.02; P=0.037), and BOO (OR, 2.27; 95% CI, 1.40–3.68; P<0.001). Given that BOO showed the highest OR, the strongest correlation was observed between bladder trabeculation and BOO.
ROC analysis was conducted using each trabeculation grade as a cutoff to determine which trabeculation grade provided the most predictive criteria for suggesting BOO (Fig. 3). When classified by the presence of trabeculation (grade 1 or higher), the area under the curve (AUC) was relatively low at 0.68 (95% CI, 0.65–0.71; P<0.001). In contrast, when classified by the presence of moderate or severe trabeculation (grade 2 or high-er), the AUC was 0.72 (95% CI, 0.69–0.75; P<0.001), and when classified by the presence of severe trabeculation (grade 3), the AUC was 0.73 (95% CI, 0.69–0.78; P<0.001), demonstrating superior predictive capacity compared to classification based solely on the presence or absence of trabeculation.
Receiver operating characteristic (ROC) analysis between bladder outlet obstruction (BOO) and bladder trabeculation grade. (A) ROC analysis between BOO and patients with bladder trabeculation (any grade: AUC=0.68, 95% CI, 0.65–0.71, P<0.001), (B) ROC analysis between BOO and patients with moderate or severe bladder trabeculation (grade 2 or 3: AUC=0.72, 95% CI 0.69–0.75, P<0.001), (C) ROC analysis between BOO and patients with severe bladder trabeculation (grade 3: AUC=0.73, 95% CI 0.69–0.78, P<0.001). AUC, area under the curve; CI, confidence interval.
In the ROC analysis for detecting moderate trabeculation (grade 2 or higher), the optimal cutoff value based on the Youden index was a BOO index of 37. At this threshold, the sensitivity was 71.0% (95% CI, 66.3–75.3) and the specificity was 62.5% (95% CI, 59.5–65.4). This cutoff closely approximates the established BOO threshold of 40.
DISCUSSION
To our knowledge, this study is the first large-scale systematic analysis of the relationship between bladder trabeculation and BOO in BPH patients. Our analysis of 1,452 BPH patients demonstrated that BOO index showed a linear correlation with trabeculation severity, and moderate or severe trabeculation (grade 2 or higher) provided high diagnostic value in predicting BOO status. These findings support BOO as an important factor inducing structural change of bladder.
The progression of BPH exacerbates BOO [16]. This process induces functional and structural bladder deterioration, starting from the initial hypertrophy phase through the subsequent compensation phase, and ultimately aggravating to the decompensation phase in more severe cases [17]. Bladder trabeculation represents the structural manifestation associated with this progression. The pathogenesis of bladder trabeculation is explained by compensatory hypertrophy of the detrusor muscle and structural remodeling [18]. Persistent high-pressure voiding due to BOO induces hypertrophy of detrusor smooth muscle cells, causing increased collagen deposition and decreased elastic fibers, thereby resulting in abnormal structural alterations of the bladder wall, trabeculation [19-22]. The increase of PdetQmax and BCI according to higher trabeculation grade in our results reflects these pathophysiological alterations (Table 2).
However, progression to the decompensation phase with the advanced BPH patient alters the neural-detrusor response, resulting in changes in bladder filling sensation and diminished bladder contractility [19, 23, 24]. Clemow et al. [25] demonstrated that chronic obstruction modifies neural-detrusor responses, thereby inducing overactive bladder symptoms. In our multivariable logistic analysis, detrusor overactivity was independently associated with trabeculation (Table 3), indicating that neurogenic remodeling occurs with trabeculation formation, leading to functional bladder deterioration. Evidence of this functional deterioration was also confirmed in Table 2, where high trabeculation grade was associated with elevated PVR and increased proportion of terminal-type detrusor overactivity.
As shown in Fig. 2, no significant correlation was observed between the BOO index and bladder trabeculation grade in patients without BOO. These findings suggest that bladder remodeling does not occur in a linear manner with increasing BOO index [20, 22]. Instead, structural changes likely require sustained chronic exposure to elevated intravesical pressure above a certain threshold, rather than transient or mild increases.
Our results provide critical evidence for establishing treatment strategies in BPH patients with BOO. Functional deterioration of the bladder upon entering the compensation phase induces detrusor overactivity and voiding symptoms such as increased daytime frequency and urgency. As BOO progresses and the bladder enters the decompensation phase, bladder compliance and detrusor muscle contractility decreases, induc-ing PVR increase and voiding symptoms such as slow stream and hesitancy. Therefore, timely aggressive therapeutic intervention is required to prevent irreversible deterioration of the bladder function, and bladder trabeculation grade may serve as a reference for treatment timing by providing information regarding BOO progression. In the multivariable logistic analysis of our study, BOO demonstrated the strongest association with bladder trabeculation among various urological parameters (Table 3). Particularly, considering the predictive value shown in Fig. 3, moderate or higher grade trabeculation strongly indicates the presence of significant BOO; therefore, active surgical management should be considered in such patients.
Previously, El Din et al. [7] conducted urological examinations including transrectal ultrasonography, urodynamic investigation, and flexible cystourethroscopy in 492 elderly men presenting with voiding complaints, demonstrating an association between BOO severity and increased bladder trabeculation grade. However, El Din et al. conducted investigation in a Western population presenting with voiding symptoms. We conducted this study in Asian individuals, who are known to have relatively smaller prostate volumes with comparable prevalence of LUTS [26], also demonstrating that BOO was significantly associated with trabeculation grade. El Din et al. used the linear passive urethral resistance relation (PURR) proposed by Schäfer to classify the severity of BOO [14]. Our study adopted BOO index, which is the current standard to determine BOO. Furthermore, they did not objectively evaluate bladder trabeculation grade. Conventional grading systems of bladder trabeculation were limited by their approximate assessment without established criteria, potentially yielding divergent subjective results at borderline values depending on urologists performing cystourethroscopy.
Our study has several strengths. First, objective data analysis was conducted in a large-scale patient cohort of 1,452 subjects. UDS data were interpreted according to standardized contemporary protocols and criteria [11], along with cystourethroscopy data evaluated using the objective grading system of bladder trabeculation established in our previous studies [8, 9]. Second, whereas previous studies proposing trabeculation grading systems included neurogenic bladder patients [8, 9, 27], our study focused on BPH patients, thereby more clearly demonstrating the association between BOO and trabeculation.
However, our study has limitations. First, our study is a retrospective, single-center study. Given the characteristics of our institution, a substantial proportion of cases was following unsuccessful or delayed primary treatment at local urology clinics. These individuals are likely to have a higher rate of severe trabeculation compared to the general population due to their exposure to relatively long-term worsening of LUTS and chronic high-pressure voiding, which may cause bias in interpretation relative to the general population. Second, according to standard clinical practice, cystourethroscopy and UDS were not performed in cases where LUTS are not severe. Patients who did not undergo full work-up based on clinical judgment were not included in this study cohort, presenting the possibility of selection bias. Third, inter-observer reliability for bladder trabeculation grading was not reassessed, although the grading system had been previously validated with excellent reproducibility [8]. Fourth, the causal interpretation between BOO and bladder trabeculation was not statistically demonstrated in this study despite their relationship. However, BOO leads to bladder remodeling, subsequently causing the formation of trabeculation from pathophysiological perspective [20-22]. Further research will provide statistical evidence of the causality between BOO and bladder trabeculation.
In conclusion, our results showed that the severity of BOO is positively associated with the severity of bladder trabeculation. Our results support that BOO induces structural as well as functional changes in the bladder.
SUPPLEMENTARY MATERIAL
Supplementary Table 1 is available at https://doi.org/10.5213/inj.2550362.181.
Bootstrap-based 95% confidence intervals for clinical parameters according to bladder trabeculation grade
Notes
Grant/Fund Support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Research Ethics
The study protocol was approved by the Institutional Review Board (IRB) of Seoul National University Hospital (IRB No. 2411-086-1587).
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
AUTHOR CONTRIBUTION STATEMENT
· Conceptualization: SWS, SJO
· Data curation: SWS, HML, GML
· Formal analysis: SWS, SJO
· Funding acquisition: SJO
· Methodology: SWS, SJO
· Project administration: SWS, SJO
· Visualization: SWS
· Writing - original draft: SWS
· Writing - review & editing: SWS, SYC, SJJ, SJO
