Despite increasing interest in detrusor underactivity (DU), its pathophysiology remains unclear. In addition, since invasive tests are usually performed for the diagnosis of DU, the development of less invasive techniques is required, such as the use of urinary biomarkers. DU usually develops after radical hysterectomy. The aim of this study was to evaluate lower urinary tract dysfunction after radical hysterectomy via a urodynamic study and identify urinary biomarkers for DU based on proteomics analysis.

This was a single-center, prospective study. Female patients undergoing nerve-sparing radical hysterectomy for cervical carcinoma were enrolled in the study. The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form were evaluated at the time of the urodynamic study. Urethral pressure profiling (UPP) and a pressure flow study (PFS) were performed before surgery and at 1 and 6 months post-surgery. Detrusor contractility was assessed using the projected isovolumetric pressure (PIP1). Moreover, using urine samples obtained at the time of the urodynamic study, a proteomics study was performed. Correlation analysis was performed to investigate the relationship between the changing ratio of pre- to postoperative (6 months) PIP1 and urinary protein levels to identify urinary biomarkers for DU.

Twenty-five patients were included in the study. Their mean age was 46±12 years. The total IPSS significantly increased 1 month after surgery and thereafter decreased 6 months after surgery. The changes in the OABSS also showed a similar tendency. The UPP showed that the maximum urethral closure pressure significantly decreased 1 month after surgery but remained at the same over the next 5 months. The PFS indicated that the first urge to void and maximum cystometric capacity were increased both 1 and 6 months after surgery. PIP1 and voiding efficiency were decreased 1 month after surgery but improved 6 months post-surgery (Table 1). The proteomics study indicated that the changing ratio of pre- to post-operative urinary moesin, ezrin, and transthyretin were significantly correlated with the changing ratio of pre- to post-operative PIP1 (r=-0.85, -0.70, and -0.68; p=0.01, 0.03, and 0.02, respectively) (Table 2). The optimum cutoff values of these proteins to diagnose DU (PIP1 <30) based on receiver-operating characteristic curves were 8.8×105 (area under the curve [AUC], 0.84; 95% confidence interval [CI], 0.68–1.00) for moesin, 1.2×106 (AUC, 0.87; 95% CI, 0.72–1.00) for ezrin, and 1.2×106 (AUC, 0.70; 95% CI, 0.50.0.90) for transthyretin.

These results indicate that (1) bladder contractility is impaired 1 month after radical hysterectomy but improves 6 months after the surgery; (2) bladder sensation, as well as urethral function, are impaired 1 month after radical hysterectomy and remain impaired 6 months after surgery; (3) urinary moesin, ezrin, and transthyretin increase in association with the impairment of bladder contractility; and (4)  optimum cutoff values of these proteins for the diagnosis of DU can be determined.

Our study demonstrates that nerve-sparing radical hysterectomy tends to cause impaired detrusor contractility and urethral function. Urinary moesin, ezrin, and transthyretin may be related to the pathophysiology of DU and could be useful urinary biomarkers for the diagnosis of DU.