Bladder wall thickness and detrusor wall thickness can help to predict the bladder outlet obstruction in men over the age of 70 years with symptomatic benign prostatic hyperplasia

The evaluation of lower urinary tract symptom/benign prostatic hyperplasia (BPH) has relied on the urodynamic study as the gold standard diagnostic test of bladder outlet obstruction (BOO) [1]. However, urodynamic studies are invasive and expensive when compared to other diagnostic tools and require the expenditure of much effort by the examiner, in terms of quality control and management, to obtain accurate results [2]. Moreover, the possibility of complications, such as urinary tract infection, hematuria, and urinary retention, following a urodynamic study frequently necessitates the prescription of additional medications, including antibiotics, before and after the examination [3].

Researchers have attempted to overcome these limitations of urodynamic studies by consistently reviewing potential alternative tests. The most recent method of note involves the measurement of bladder wall thickness (BWT) and detrusor wall thickness (DWT) using transrectal or transabdominal ultrasonography. Several studies have reported a positive relationship among BWT, DWT and BOO, based on urodynamic studies in men with symptomatic BPH [4, 5, 6, 7].

Our research team recently performed and published a preliminary study indicating that the resolution of BOO after BPH surgery is accompanied by a decrease in DWT. However, we were unable to confirm any positive association between DWT and BOO because of the small number of subjects in that study [5]. During that preliminary study, we maintained the same measurement conditions before and after surgery by assessing BWT and DWT by checking the post-void residual urine volume after uroflowmetry. We have since included BWT and DWT measurement after uroflowmetry as a routine diagnostic procedure for evaluating BPH surgery candidates, and we have continuously added to the database.

The aim of the present study was to investigate the relationship among preoperative BWT, DWT and BOO based on urodynamic studies in men with symptomatic BPH to confirm whether assessment of BWT/DWT could replace urodynamic studies.

We reviewed a BPH surgery database prospectively collected between October 2012 and November 2016. A total of 196 men who underwent prostate vaporization for symptomatic BPH were included in this study. Patients with previous pelvic radiotherapy/surgery, previous diagnosis of prostate cancer, or neurological diseases were excluded from the analysis. All patients underwent a preoperative standard diagnostic assessment, including medical history and physical examination, and they filled out the international prostate symptom score (IPSS)/quality of life (QoL) questionnaire. Additional interventions consisted of blood tests, including tests for prostate specific antigen (PSA), and specialized studies, such as uroflowmetry, post-voided residual urine volume determinations, transabdominal/transrectal ultrasonographic measurements of prostate size, BWT, DWT, and multichannel urodynamic studies.

BWT and DWT values were simultaneously assessed by suprapubic ultrasonography (7.5 MHz, SA-8000; Medison, Seoul, Korea) (Fig. 1). All sonographic examinations were performed by a single experienced radiologist during the postmicturition state after uroflowmetry. BOO was defined as a BOO index >40 (Pdet @ Q_max−2 Q_max), determined from the urodynamic study. We divided all patients into two groups based on age (<70 years old or ≥70 years old) and conducted a subgroup analysis according to the age group.

Fig. 1
BWT and DWT measurements in the same subject after uroflowmetry. BWT, bladder wall thickness; DWT, detrusor wall thickness.

• Click for larger image
• Download as PowerPoint slide

The study protocol was approved by the Institutional Review Board at SMG-SNU Boramae Medical Center (approval number: 16-2015-77) and the study conformed to the tenets of the Declaration of Helsinki. The planned study was explained to the patients in detail, and written informed consent was obtained from each patient.

The mean age of the patients was 69.5±6.9 years, and the mean body mass index was 24.2±2.8 kg/m². Thirty-seven (18.9%) patients had diabetes mellitus, and 91 (46.4%) had hypertension. The mean total prostate volume and transitional zone volume was 55.8±27.8 mL and 33.6±22.4 mL, respectively. Suprapubic ultrasonography yielded a mean value of 2.6±0.9 mm for DWT and 3.4±1.1 mm for BWT. The preoperative mean PSA was 5.4±4.7 ng/mL. The preoperative total IPSS was 20.5±8.8, and the voiding symptom subscores and storage symptom subscores were 12.4±5.8 and 8.2±3.9 respectively. The QoL score was 4.2±1.3. The preoperative mean Q_max was 8.5±4.4 mL/s, and the preoperative mean post void residual urine was 70.5±96.6 mL. The preoperative urodynamic study revealed a mean maximal urethral closure pressure of 76.5±30.2 cmH₂O and a maximum cystometric capacity of 346.7±121.9 mL. Poor bladder compliance and involuntary detrusor contraction were present in 21 (10.7%) and 112 (57.1%) patients, respectively. BOO index was 40.8±32.6, and 84 (42.9%) patients were classified as obstructed (Table 1).

Table 1
Patient characteristics

• Click for larger image
• Click for full table
• Download as Excel file

BWT and DWT values were relatively thicker in the obstruction group; however, statistical significance was not reached in all patients. Subgroup analysis showed that BWT and DWT were significantly thicker in the obstruction group in men aged 70 years or older (BWT: 3.6+0.9 mm vs. 3.1+0.9 mm, p=0.022, DWT: 2.8±0.8 mm vs. 2.3±0.8 mm, p=0.007) (Table 2).

Table 2
BWT, DWT and PVR according to the BOO index and age groups

• Click for larger image
• Click for full table
• Download as Excel file

In univariate analysis, PSA, prostate volume, and voiding symptom subscore were associated with BOO. In men aged 70 years or older, body mass index, prostate volume, voiding and storage symptom subscore, BWT and DWT were related to BOO. Multivariate analysis revealed prostate volume (odds ratio [OR], 1.031; p=0.039) and Q_max (OR, 0.791; p=0.037) are important parameters for predicting BOO, whereas DWT showed the tendency associating with BOO in the older age group (OR, 2.429; p=0.069) (Table 3).

Table 3
Univariate and multivariate analysis for predicting BOO

• Click for larger image
• Click for full table
• Download as Excel file

In all patients, the classification by BWT ≥4 mm showed 36% sensitivity, 78% specificity, 55% positive predictive value, 62% negative predictive value, and 60% diagnostic accuracy for the diagnosis of BOO. Subgroup analysis for the men aged 70 years or older showed that BWT ≥4 mm gave 31% sensitivity, 87% specificity, 60% positive predictive values, 66% negative predictive value, and 65% diagnostic accuracy. Meanwhile, in all patients, the classification by DWT ≥3 mm showed 43% sensitivity, 75% specificity, 55% positive predictive value, 63% negative predictive value, and 61% diagnostic accuracy for the diagnosis of BOO. In men aged 70 years or older, DWT ≥3 mm showed 49% sensitivity, 82% specificity, 63% positive predictive value, 71% negative predictive value, and 69% diagnostic accuracy (Table 4).

Table 4
BOO index profiles according to BWT (4 mm) and DWT (3 mm)

• Click for larger image
• Click for full table
• Download as Excel file

A recent review article about the BWT and DWT by Bright et al. [4] concluded that a positive relationship among BWT, DWT and the BOO index had been verified consistently, but a precise reference range was still not established. DWT might be influenced by various factors, especially those affecting bladder filling. Therefore, some researchers have recommended filling the bladder with more than 150 to 200 mL normal saline before measuring BWT and DWT [8, 9, 10]. However, assessing the bladder filling status in a real clinical practice setting is very difficult. Our opinion is that the easiest situation for the patient is to perform the transabdominal ultrasonography and to measure BWT and DWT by checking the post-void residual urine volume after uroflowmetry.

In the present study, the measured values of BWT and DWT were somewhat higher than those reported in previous studies [11, 12], which could have resulted from differences in bladder filling status [13]. About 64.3% (126/196) of the patients had a post-void residual urine volume under 50 mL, whereas the men with residual urine volume ≥150 mL accounted for only 12.2% (24/196). BWT and DWT were relatively thicker in men with urine volumes under 50 mL than over 50 mL; however, the difference was not statistically significant (BWT: 3.5+1.1 mm vs. 3.3+1.1 mm, p=0.246; DWT: 2.6+0.9 mm vs. 2.4+0.9 mm, p=0.107). An additional study will be required for a larger population of patients with BOO when distributed into groups according to a residual urine volume.

The noted difference in BWT and DWT according to the age group was interesting. BWT and DWT were not statistically distinguishable in men aged less than 70 years, whereas BWT and DWT were significantly thicker in the obstruction group in men aged 70 years or older. Previous animal studies reporting that BOO led to hypertrophy of bladder [14, 15] suggested that a gradual increase in BWT and DWT after BOO had occurred. Therefore, BWT and DWT could also be decreased when BOO was resolved after BPH surgery, as observed in our previous report [5]. BWT and DWT would also be a significant parameter in men who had suffered from obstructive symptoms for a long time.

More than 10 years have passed since the hypothesis was first suggested that BWT and DWT measurements could replace urodynamic studies, but a simple and precise measurement method for BWT and DWT determination has not been established. Oelke et al. [12, 13] measured DWT during a filling cystometrogram, a part of the urodynamic study, and for that reason, they also reported the change in DWT according to the bladder filling volume. However, their measurement method was not appropriate for the practical application of BWT and DWT. In other words, if we had to measure the BWT and DWT during the urodynamic study for the confirmation of substitution of urodynamic study, this did not serve the purpose of reducing the need for the invasive urodynamic study; rather, it was just an interesting line of academic research. Another consideration was that artificial filling via a urethral catheter could affect the physiology of bladder, BWT and DWT when compared to natural filling. By all accounts, measurements of BWT and DWT during a check of the post-void residual urine volume after uroflowmetry could be practical and useful and would add no extra cost or time consumption for the patients.

In this study, we suggested values of BWT ≥4 mm and DWT ≥3 mm as cut-off values for the diagnosis of BOO. These values were determined based on a receiver operating characteristic curve and consideration of the convenience of clinical application. However, the diagnostic accuracy of BWT and DWT did not reach a dependable level, which might reflect a statistical problem because of the low number of subjects, especially in the older age group. The accuracy of urodynamic studies for the diagnosis of BOO should be discussed [16].

Although we used a prospectively collected BPH surgery database with original rationales, the study has some limitations. First, a relatively small number of patients were included in the subgroup analysis. In particular, the number of subjects with BOO was small, so this might have biased the statistical analysis. Second, although measuring BWT and DWT was performed under the standard urologic ultrasonographic guideline by a single experienced radiologist, the additional confirmation of the time-dependent and inter-observer stability during the examination should be included in the future study. It is impossible to conclude BOO based solely on BWT and DWT. Nonetheless, checking the bladder and measuring BWT and DWT via ultrasonography may be useful in clinical practice in the initial evaluation of BPH patients. As mentioned in the results part, because patients with the thicker BWT/DWT in the initial workup would have a higher chance to show BOO, this information might be helpful to decide the treatment plan.

BWT and DWT values were significantly associated with BOO in men aged 70 years or older. BWT and DWT therefore represent a useful non-invasive parameter for deciding management strategies in elderly men with symptomatic BPH. An appropriate measurement method should be established as soon as possible for further application of the relationship among BWT, DWT and BOO index.