Factors Associated with Urethral and Bladder Neck Stricture After Transurethral Resection of the Prostate

Introduction

Transurethral resection of the prostate (TURP) is the surgical gold standard for the treatment of prostatic hyperplasia (PH); however, the procedure is not exempt from complications, either during surgery or postoperatively. Transoperative complications include post-TURP syndrome, bladder and prostatic capsule perforation, and injury of the external urethral sphincter. The most frequent postoperative complications reported are urinary tract infection (UTI), urinary incontinence, urethral stricture, bladder neck stricture, erectile dysfunction, and retrograde ejaculation. ^1,2

The incidence of urethral stricture following TURP is reported between 1.7 and 9.8%, ^3,4 while bladder neck stricture is between 0.3% and 9.2%. ¹ These complications have long-term and detrimental consequences as they compromise the patient's quality of life.

According to several studies, the most relevant risk factors in the development of urethral and bladder neck stricture (U/BNS) secondary to surgical management include prolonged surgical duration, asymptomatic prostatitis, ⁵ diameter of the resectoscope, ⁶ prostatic volume, ⁷ time of resection, and postoperative UTI. ⁸ At our hospital, TURP is performed with monopolar energy, thus avoiding prolonged surgical time and patients with larger prostates. Nevertheless, undesired events such as U/BNS develop, suggesting that there are other factors predisposing patients to this complication.

The aim of this study is to analyze risk factors associated with the development of stricture of the urethra and bladder neck following TURP.

Materials and Methods

Prior authorization by the hospital's Ethics Committee, we conducted a case–control study, with two controls per case. This study (IRB Approval R-2019-1912-026) took place in a public hospital in the northeastern region of the country. Population: patients who underwent monopolar TURP using a 1.5% glycine irrigation solution.

Sample size was calculated for each analyzed factor and the largest number of patients was used to reasonably analyze all risk factors, with an alfa type error of 0.05% and a power of 80%, two control patients were taken for each case, with an ideal sample size of at least 83 cases and 187 controls to obtain a proper statistical power.

Cases were selected consecutively in a nonrandomized manner and included all patients with U/BNS following TURP diagnosed between January 2010 and December 2018, until sample size was achieved. We used the following inclusion criteria: the definition of U/BNS refers to patients with obstructive symptoms after TURP, with evidence of urethral or bladder neck stenosis by imaging studies (urethrocystography), direct visualization of the stenotic ring during urethroscopy, or clinically with the inability to introduce a 16F urethral catheter. Controls were selected with EXCEL random numbers, among patients operated between January 2016 and December 2017, that were followed for over a year and with no clinical or imaging evidence of stricture. Patients with a previous history of U/BNS and/or pelvic fracture were excluded, as well as those with strictures detected in the initial urethroscopy.

The following personal risk factors were included: age, prostatic volume measured by abdominal ultrasound, history of diabetes mellitus, previous use of a transurethral catheter (transient or permanent), history of UTI before surgery, bladder calculi at the time of TURP, prostate cancer, and a history of previous TURP. The factors associated with the surgical procedure were resection time, resected volume, transoperative complications (bleeding, bladder perforation, or false urethral passage), and number or surgical procedures performed during the same event such as resection of a bladder tumor or transrectal prostate biopsy. These data were obtained from the hospital's electronic clinical chart and had been entered by the treating urologist.

Results

A total of 680 patients with U/BNS were detected between 2010 and 2018; 194 (29%) cases were secondary to TURP, 127 (19%) were classified as idiopathic, 42 (6%) presented U/BNS at the time of TURP, and 129 (19%) patients could not be classified. In the remaining 188 (27%) patients, several causes were determined as the cause of stricture: simple or radical prostatectomy, prolonged urethral catheter placement, urethral trauma, iatrogenic, lithuria, and transurethral resection of a bladder tumor. Patients with stricture secondary to TURP that adequately fulfilled all required criteria were selected as cases. A total of 577 patients underwent TURP between January 2016 and December 2017, and those that fulfilled the necessary criteria were randomly selected as controls until the appropriate sample size was achieved.

A total of 308 patients were studied: 101 cases and 207 controls. In both groups, the surgeries were performed by the attending urologist or fourth-year urology residents.

The two most frequent stricture locations were bulbar urethra (26.7%) and urethral meatus (19%), the other locations are summarized in Table 1. The median time to diagnosis of post-TURP stricture was 6 months (minimum 3, maximum 13 months). On bivariate analysis, cases had a lower prostatic volume than controls (55 vs 63 g, p = 0.012), lower surgical resection time (30 vs 40 minutes, p = 0.014), lower grams resected (22 vs 24 g, p = 0.048), lower prostate-specific antigen (PSA) values (4.25 vs 6.1, p = 0.023) and lower incidence of prostate cancer (7% vs 17%, p = 0.017). Patients without U/BNS had an increased frequency of transurethral catheter placement before the surgical procedure (46% vs 29%, p = 0.004). There were no differences between groups in the other analyzed factors, such as age, presence of bladder calculi, history of diabetes mellitus, multiple urological procedures in the same intervention, history of TURP, surgical complications, and history of UTI (Table 2). On multivariate analysis, all variables with a p ≤ 0.05 were included, and the use of a urethral catheter (permanent or transient) was determined as a protective factor against U/BNS (OR 0.16, 95% CI 0.064–0.442, p < 0.001) (Table 3).

Discussion

TURP is the most frequent surgical treatment for patients with PH, which may lead to long-term complications such as U/BNS in up to 9% of cases. ¹ The aim of this study was to identify risk factors associated in the development of U/BNS.

Most studies that have analyzed possible factors associated with this complication have excluded patients with certain pathologies that do not necessarily reflect the common daily practice scenario.

This study found no association between bladder calculi or the use of a transurethral catheter and the risk of U/BNS. Based on these findings, we must reconsider that in addition to the inflammatory reaction resulting from the presence of a foreign body in the urothelium that can promote fibrosis and stricture after the surgical procedure, there may be multiple factors involved in the development of this pathology.

No association was detected in our study with factors reported in other studies, such as the prostatic volume and resection time, in the development of U/BNS after TURP. In a study by Grechenkov and others, ⁷ the authors determined the mean prostatic volume in patients without stricture was 60 vs 70 cm³ in patients with stricture (p = 0.005). These results contrast those published by García and colleagues ⁹ who reported that patients with urethral stricture had a lower prostatic volume than patients without stricture (63 vs 87 g, p = 0.005). In our study, cases had a lower prostatic volume than controls (55 vs 63 g, p = 0.012), but this difference lost relevance on multivariate analysis; still, this could be explained by excessive resection either at the level of the bladder neck or very close to the capsule in smaller prostates, leading to greater chance of capsular injury or fluid extravasation.

Prolonged resection time has also been reported as a risk factor associated with U/BNS. In a study by Doluoglu et al., ⁵ patients whose resection lasted over 60 minutes were at greater risk of requiring surgical reintervention for the management of U/BNS (OR 4.27, 95% CI 1.63–11.21). In our patients, cases had lower resection times, lower grams resected (as well as lower prostatic volume), but these differences were not significant on multivariate analysis. Shorter resection times in patients with stricture may be related with smaller prostates or the early termination of surgery due to a surgical complication.

Up to a third of patients who undergo a TURP have a history of prior use, temporarily or permanently, of a transurethral catheter. Although it has been argued that the catheter causes an acute inflammatory reaction due to latex, ¹⁰ there are no conclusive results suggesting that this is a predisposing factor to the development of stricture, regardless of how long the catheter has been in place before or after surgery, nor its caliber. ¹¹ Jorgensen et al., found an increased incidence of urethral stricture in patients requiring a preoperative catheter, although the statistical value was not significant (13% vs 7%, p > 0.05). Among patients with a catheter, the incidence of stricture increased if the catheter was in place for less than 7 days when compared with patients who required it for a longer period of time (21% vs 9%, p = <0.05). ¹⁰ Grechenkov and coworkers found no association between the previous use of a transurethral catheter or cystostomy and the presence of urethral stricture, although its incidence was greater in patients with this antecedent (29.5% vs 17.9%, p = 0.32). ⁷

Among the patients included in this study, 40% required a transurethral catheter before surgery (either temporal or permanent), and its use appeared to be a protective factor in the development of stricture, 29% of cases vs 46% in controls (OR 0.17, 95% CI 0.074–0.416, p < 0.001). These results coincide with those previously reported by García-Villa and others, ⁹ who analyzed patients with and without urethral stricture after TURP, and detected that this complication developed in 36.7% of patients with prior use of a transurethral catheter vs 69.7% in those who did not (p = <0.005).

Friction and possible urethral mucosal injury generate an inflammatory reaction that, over time, may lead to stricture. Günes and associates ⁶ reported an incidence of postoperative urethral stricture of 8.6% in patients intervened with 24F equipment vs 13.9% in those operated with 26F equipment; the statistical difference was specific to the bulbar urethra (2.9% vs 11.4%, p = 0.018). Most patients included in this study were intervened with 26F equipment; however, due to retrospective data collection, resector caliber could not be analyzed as a risk factor.

In general, patients with a permanent urethral catheter who undergo a TURP tend to have a more compliant urethra, resulting in less friction when introducing the resectoscope. Supporting this finding, Jorgensen and others ¹⁰ found that patients who required a catheter for more than 7 days had a lower incidence of stricture compared with those who used it for a shorter period. The possible explanation for this result and ours is that the first may have a more compliant urethra, leading to less friction when introducing the resectoscope and subsequent less injury to the urethral mucosa. In this study, it was not feasible to determine how long the period of urethral catheterization is necessary to act as a protective factor for U/BNS, since it was not possible to collect information about the days of catheter use in our patients.

Patients undergoing TURP in whom the introduction of the resectoscope is difficult, it is preferred to place a Foley catheter and perform the procedure once the urethra allows proper insertion of the equipment, without injuring the mucosa.

Among our study's limitations, since it is retrospective in nature, data such as the development of surgical complications, time of resection, and resected volume, may be subjective; also, there may be some clinical points that could have been omitted in the clinical records. Prostate volume was obtained by abdominal ultrasound in almost all cases, so interobserver variability may play a role in its interpretation. A bias in our study was the great number of surgeons, since surgeries were performed by attending personnel and residents from the Urology department.

In the control group, there was a higher proportion of patients with prostate cancer, although statistically significant, when it was introduced in multivariate analysis, lost its statistical power. This difference may be secondary to several factors such as selection bias due to the timeline difference between case and controls, lack of information on clinical records, and because prostate cancer treatment modalities change continuously over the years. Previously, in the study carried out by Jorgensen and coworkers, ¹⁰ no difference was found in stricture incidence in prostate cancer patients; however, more clinical research is needed to address whether prostate cancer is associated with U/BNS.

Catheterized patients had higher PSA levels, and despite this difference, the presence of prostate cancer was similar in both groups (data not showed); this finding can be explained by the history of urinary tract instrumentation.

All data were obtained by the main investigator, so selection bias may exist in the inclusion of patients in each study group. Controls and cases do not belong to the same timeline, as this was preferred to avoid data loss in the control group patients.

Imaging studies or cystoscopy are not usually performed at our hospital if the patient's clinical course is favorable, without obstructive symptoms after TURP; therefore, we cannot exclude the possibility that there are patients with stricture but without clinical manifestations included in the control group.

Among the studies reviewed, ours included the greatest number of patients with urethral stricture, with a sample size and statistical power that are sufficient to objectively analyze all possible risk factors included in the analysis. A prospective study is necessary, with a greater sample size, to objectively analyze all possible risk factors associated with the development of U/BNS.

Conclusions

We were unable to identify risk factors associated with the development of U/BNS after TURP; however, the use of a Foley catheter before the TURP was found to be a protective factor for the development of stricture.