De novo overactive bladder after robot-assisted radical prostatectomy is predicted by a high preoperative overactive bladder symptom score, preoperative dyslipidemia, and non-nerve-sparing surgery

Abstract

Objectives: This study investigated whether preoperative patient characteristics and surgery-related factors affect postoperative de novo overactive bladder (OAB) after robot-assisted radical prostatectomy (RARP), and identified three predictive markers.

Methods: Patients without preoperative OAB who underwent RARP at our hospital between February 2013 and October 2020 were included.　At 12 months post-RARP, patients were divided into OAB-free and de novo OAB groups based on the presence of overactive bladder.　Preoperative patient characteristics and surgery-related factors were compared between the two groups.

Results: A total of 404 patients were analyzed (OAB-free group, 338; de novo OAB group, 66).　The preoperative Overactive Bladder Symptom Score (OABSS) and the percentage of patients with dyslipidemia were significantly higher in the de novo OAB group than in the OAB-free group (OABSS, 3.2 ± 1.6 points vs 2.1 ± 1.4, P<0.01; dyslipidemia, 45.5% vs 32.0%, P=0.04).　Nerve-sparing surgery was significantly less common in the de novo OAB group (10.6% vs 27.1%, P<0.01).　Preoperative age, blood pressure, BMI, HbA1c, uroflowmetry parameters, prostate volume, operative time and blood loss showed no significant differences between two groups.

Conclusions: High preoperative OABSS, preoperative dyslipidemia and non-nerve-sparing surgery may be predictive markers for de novo OAB after RARP.

Introduction

Robot-assisted surgery has been widely adopted in urology; in particular, robot-assisted radical prostatectomy (RARP) for localized prostate cancer is emerging as a gold standard procedure in Japan, the United States, and Europe.　A robotic surgical system can provide 10-fold magnification with a 3-dimentional perspective.　With this view, an operator can remotely control a robotic arm by manipulating its control lever.　The forceps tip of a robotic arm with joint mobility of 70 degrees and a high degree of freedom allows precise and delicate surgical operations.　Therefore, robot-assisted surgery enables shorter operating time, less blood loss, fewer complications, a shorter hospital stay, and earlier return to activities of daily living, in comparison to conventional open surgery and laparoscopic surgery¹⁾.

Although the usefulness of RARP has been established, postoperative complications persist.　In particular, postoperative symptoms such as overactive bladder (OAB) and urinary incontinence remain among the main complications of RARP, causing annoyance to patients and remarkably reducing their quality of life^1-3).

OAB is a complex of storage symptoms including urgency with or without urinary incontinence, usually with frequency and nocturia, and poorly defined pathophysiology⁴⁾.　OAB has a negative impact on quality of life.　De novo OAB is the postoperative development of OAB that was not observed preoperatively.　Some patients have de novo OAB after RARP^5,6).　Although de novo OAB may be attributed to the operative procedure itself, preoperative patient characteristics may also contribute to the onset of de novo OAB after RARP.　If risk factors for de novo OAB can be identified preoperatively, patients can be given more appropriate information before RARP is performed.　This study investigated whether preoperative patient characteristics predict the development of de novo OAB after RARP.

Materials and methods

Patients

Patients who underwent RARP for localized prostate cancer at our hospital between February 2013 and October 2020 were included in this study.　Patients with organ-confined prostate cancer were considered to be candidates for RARP.　Specific inclusion criteria were 1) clinically localized or locally advanced prostate cancer, 2) age <75 years, and 3) an Eastern Cooperative Oncology Group performance status of 0.　During this period, 671 patients underwent RARP.　Among these patients, those who had preoperative OAB, or were diagnosed with OAB by OABSS, or were taking medications for OAB on admission, were excluded.　This study was approved (No. 2022-113) by the Ethics Committee of Fukushima Medical University Hospital, which is guided by local policy, national law, and World Medical Association Declaration of Helsinki.　Informed consent was documented in writing.

Study design

At 12 months after RARP, patients were assigned to the OAB-free group or the de novo OAB group according to the absence or presence of OAB.　Preoperative patient characteristics, including age, systolic and diastolic blood pressure (measured in the sitting position on the morning of admission for RARP), obesity (BMI ≥ 25 kg/m²), dyslipidemia (LDL-C/HDL-C ratio ≥ 2.5), HbA1c, overactive bladder symptom score (OABSS), uroflowmetry parameters, post-void residual urine volume (PVR), bladder voiding efficiency (BVE), prostate volume, and surgery-related factors such as operative time, blood loss, and nerve preservation were compared between the OAB-free and de novo OAB groups.

The OABSS is an assessment tool designed to quantify OAB symptoms with a single score⁷⁾.　The OABSS consists of 4 questions about daytime frequency, night-time frequency, urgency, and urgency incontinence.　The maximum scores of each are 2, 3, 5 and 5, respectively.　Higher OABSS scores indicate a worse result.　The total score could therefore range from 0 (best) to 15 (worst), with a higher score indicating increasing symptom severity.　In this study, OAB was defined as a total OABSS score ≥3 with an urgency score ≥2.

Uroflowmetry was performed to obtain maximum flow rate (MFR), average flow rate (AFR), and voiding time.　BVE is a measure of bladder emptying, defined as the ratio between voided volume and total bladder capacity.　PVR and prostate volume were determined by trans-abdominal ultrasonography.

Surgical technique

RARP was performed using a four-arm da Vinci Si™ surgical system (Intuitive Surgical Inc., Sunnyvale, CA, USA) by the transperitoneal posterior approach reported by Guillonneau et al. in conventional laparoscopic procedures⁸⁾.　This approach is initiated with transverse peritoneotomy between the bladder and rectum, followed by retrovesical dissection.　After dissection of the bladder neck, prostatic vascular pedicles are ligated and the prostate is removed.　Nerve-sparing surgery was only performed in patients with low or favorable intermediate-risk prostate cancer who requested it.　Posterior reconstruction was performed on all cases in the present study.　Vesicourethral anastomosis was conducted using the Van Velthoven procedure.　RARP was performed or supervised by a single surgeon (Y.K.), who has performed more than 100 RARP procedures.

Statistical analysis

All values are expressed as mean ± standard deviation.　The chi-square test was used for analysis of categorical variables, and the Mann–Whitney U test was used for continuous variables.　P-values of <0.05 were considered to be statistically significant.　All data were analyzed using IBM SPSS Statistics for Windows, Version 24.0 (IBM Corp., Armonk, NY, USA).　ROC analysis was performed to determine a preoperative OABSS predictive of de novo OAB development, with the cut-off value set at the point on the ROC curve closest to the left-upper corner of the unit square.

Results

Of the 671 prostate cancer patients who underwent RARP between February 2013 and October 2020, those without preoperative OAB (404 of 671, 60.2%) were ultimately included in this study.　The background of these patients is shown in Table 1.

The 404 study patients (67.0 ± 5.3 years) were divided into two groups: those without OAB at 12 months postoperatively (OAB-free group: 338 patients, 83.7%) and those with OAB (de novo OAB group: 66 patients, 16.3%).

We compared preoperative patient characteristics including age, systolic blood pressure, diastolic blood pressure, obesity, dyslipidemia, and HbA1c.　The percentage of patients with dyslipidemia was significantly higher in the de novo OAB group than in the OAB-free group (45.5% vs 32.0%, P=0.04).　The preoperative age, blood pressure, BMI, and HbA1c were not significantly different between the two groups (Fig. 1).　We also compared the preoperative parameters of low urinary tract symptoms and function, including OABSS, uroflowmetry parameters, post-void residual (PVR), bladder voiding efficiency (BVE), and prostate volume between the OAB-free and de novo OAB groups.　The total OABSS was significantly higher in the de novo OAB group than in the OAB-free group (3.2 ± 1.6 points vs 2.1 ± 1.4 points, P<0.01, Fig. 2).　The uroflowmetry parameters, PVR, BVE, and prostate volume were not significantly different between the two groups (Fig. 3).

Surgery-related factors including operative time, blood loss, and nerve preservation were compared between the OAB-free and de novo OAB groups.　There were no significant differences between the two groups in terms of operative time or blood loss, but the percentage of patients who underwent nerve-sparing surgery was significantly lower in the de novo OAB group than in the OAB-free group (10.6% vs 27.1%, P<0.01) (Fig. 4).

The ROC cut-off value for preoperative OABSS, to predict de novo OAB development, was calculated to be 2.5 points (sensitivity 71.0%, specificity 59.1%, AUC 0.691, Fig. 2).

Table 1.

Background of 404 patients without preoperative OAB

Fig. 1.

Comparison of preoperative physiological factors between de novo OAB and OAB-free groups

Fig. 2.

Comparison of preoperative OABSS between de novo OAB and OAB-free groups and a cut off value of optimal accuracy in receiver operating characteristics (ROC) analysis

Fig. 3.

Comparison of lower urinary tract function and prostate volume between de novo OAB and OAB-free groups

Fig. 4.

Comparison of surgery-related factors between de novo OAB and OAB-free groups

Discussion

In this study, we examined preoperative patient characteristics possibly related to de novo OAB after RARP, and found that a high preoperative OABSS, preoperative dyslipidemia, and non-nerve-sparing surgery were predictive of de novo OAB after RARP.

The etiology of “de novo” urinary incontinence after RARP is complex and multi-factorial.　Muscle fibers of the sphincter and the nerves can be damaged and/or decreased in number after RARP, which induces urine leakage into the urethra.　Leakage into the urethra stimulates afferent nerve activity of the proximal urethra, resulting in the micturition reflex.　The micturition reflex is one cause of de novo OAB⁹⁾.　Nerve-sparing surgery might prevent de novo OAB by maintaining urethral sphincter function.　Not only surgical technique and a surgeon’s skill, but also, patient characteristics can affect continence after RARP.　Age, prostate volume, body mass index (BMI), and preoperative lower urinary tract symptoms (LUTS) may be factors influencing continence after RARP²⁾.　However, investigations of risk factors for de novo OAB after RARP are lacking.

De novo OAB is regarded as one of the major complications after RARP⁵⁾.　The prevalence of OAB after radical prostatectomy may range from 15.2 to 37.8%⁶⁾, with symptoms that reduce patient satisfaction and adversely affect health-related quality of life.　In our study, de novo OAB emerged in 16.3% of patients within 12 months of RARP.　Recent studies have highlighted the role of the urethrogenic mechanism (facilitation of the urethrovesical reflex due to stress urinary incontinence (SUI)) in the genesis of post-prostatectomy OAB in a significant proportion of patients⁶⁾.

Disturbance of the urethrogenic mechanism, iatrogenic decentralization of the bladder, defunctionalized bladder due to severe stress urinary incontinence, detrusor underactivity, and bladder outlet obstruction were considered as pathophysiological factors of de novo OAB⁶⁾.　Matsukawa et al. reported that the post-operative continence rate was significantly higher in an OAB-free group (79.7%) than in a de novo OAB group (8.0%), and demonstrated through a urodynamic study that decreased urethral function was significantly related to de novo OAB after RARP¹⁰⁾.　Because de novo OAB that occurs after RARP can be difficult to treat, it is important that patients are counselled about the potential for developing OAB before decisions regarding treatment are made¹¹⁾.　Therefore, it is quite important to identify preoperative risk factors.　Watanabe et al. have reported in a small study that patients with a high BMI may develop de novo OAB after RARP, resulting in a significant deterioration of lower urinary tract function⁵⁾.　It has been suggested that chronic pelvic ischemia with reduced blood flow to the bladder and excessive extension of the pelvic floor with increased abdominal pressure in patients with high BMI causes urethral hypermobility, leading to OAB^5,12,13).

Our research indicates that dyslipidemia contributes to de novo OAB.　Several studies have also reported that the LDL-C/HDL-C ratio more accurately predicts cardiovascular disease (CVD) risk than LDL-C or HDL-C levels alone and that an elevated LDL-C/HDL-C ratio is associated with the progression of atherosclerosis.　Recently, the LDL-C/HDL-C ratio has been used to assess dyslipidemia, with a predictive cut-off value of 2.5 for the LDL/HDL ratio¹⁴⁾.　Atherosclerosis is well known to cause OAB by contributing to chronic bladder ischemia^15-17).　We have demonstrated that chronic bladder ischemia induces bladder hyperactivity in an animal model^18-20).　Atherosclerosis delays improvement in OAB and storage function postoperatively, and it is involved in a transient increase in the prevalence of de novo OAB after RARP²¹⁾.　A preoperative elevated LDL-C/HDL-C ratio may foretell de novo OAB after RARP through chronic bladder ischemia.　Although Watanabe et al. demonstrated that BMI was risk factor of de novo OAB⁵⁾, our study did not show the same result.　This discrepancy may be due to differences in the timing of postoperative evaluations.　They evaluated OABSS at 6 months after RARP, while we evaluated it at 12 months after RARP.

Our study also demonstrated that the total OABSS before RARP was significantly higher in the de novo OAB group than in the OAB-free group.　Among the patients studied, some pre-operative bladder dysfunction was possible.　Moreover, bladder dysfunction could also coexist with sphincteric weakness after RARP¹¹⁾, and may arise due to the surgery because of partial denervation around the bladder²²⁾.　Patients with high preoperative OABSS might have potential bladder instability even without being diagnosed with OAB before RARP.　After RARP, bladder instability might become worse and apparent, resulting in de novo OAB.

Several study limitations need to be addressed.　First, this was a retrospective study at a single center.　Second, we did not perform urodynamic studies of detrusor overactivity or maximum closed urethral pressure.　Although a strength of our study is its relatively large sample size with a long follow-up time, further detailed studies, here and at other centers around the world, are warranted.

Conclusions

Our results suggested that a high preoperative OABSS, preoperative dyslipidemia, and non-nerve-sparing surgery may be predictive of de novo OAB after RARP.

References

• 1.   Yanagida T, Koguchi T, Hata J, et al. Current techniques to improve outcomes for early return of urinary continence following robot-assisted radical prostatectomy. Fukushima J Med Sci, 60: 1-13, 2014.
• 2.   Kojima Y, Takahashi N, Haga N et al. Urinary incontinence after robot-assisted radical prostatectomy: pathophysiology and intraoperative techniques to improve surgical outcome. Int J Urol, 20: 1052-1063, 2013.
• 3.   Hutchison D, Zillioux J, Ali M, et al. Predictors of urinary outcomes following robotic-assisted laparoscopic prostatectomy. BJUI Compass, 4: 722-728, 2023.
• 4.   Abrams P, Cardozo L, Fall M et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn, 21: 167-178, 2002.
• 5.   Watanabe K, Otsuka A, Sano A, et al. Predictive factors of de novo overactive bladder in clinically localized prostate cancer patients after robot-assisted radical prostatectomy. Int J Urol, 30: 57-61, 2023.
• 6.   Peyronnet B, Brucker BM. Management of overactive bladder symptoms after radical prostatectomy. Curr Urol Rep, 19: 95, 2018.
• 7.   Homma Y, Yoshida M, Seki N, et al. Symptom assessment tool for overactive bladder syndrome--overactive bladder symptom score. Urology, 68: 318-323, 2006.
• 8.   Guillonneau, B, Vallancien, G. Laparoscopic radical prostatectomy: the Montsouris experience. J Urol, 163: 418-422, 2000.
• 9.   Haga N, Ogawa S, Yabe M, et al. Association between postoperative pelvic anatomic features on magnetic resonance imaging and lower tract urinary symptoms after radical prostatectomy. Urology, 84: 642-649, 2014.
• 10.   Matsukawa Y, Yoshino Y, Ishida S, et al. De novo overactive bladder after robot-assisted laparoscopic radical prostatectomy. Neurourol Urodyn, 37: 2008-2014, 2018.
• 11.   Thiruchelvam N, Cruz F, Kirby M, et al. A review of detrusor overactivity and the overactive bladder after radical prostate cancer treatment. BJU Int, 116: 853-861, 2015.
• 12.   Dallosso HM, McGrother CW, Matthews RJ, et al. The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int, 92: 69-77, 2003.
• 13.   Pinggera GM, Mitterberger M, Steiner E, et al. Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men: assessment using colour doppler ultrasonography. BJU Int, 102: 470-474, 2008.
• 14.   Noike H, Hitsumoto T, Sakurai T, et al. Relationships between intravascular ultrasonographic findings and coronary risk factors in patients with normal coronary angiography. J Cardiol, 45: 1-10, 2005.
• 15.   Akbar A, Liu K, Michos ED, et al. Association of Overactive Bladder With Hypertension and Blood Pressure Control: The Multi-Ethnic Study of Atherosclerosis (MESA). Am J Hypertens, 35: 22-30, 2022.
• 16.   Yeniel AO, Ergenoglu AM, Meseri R, et al. Is overactive bladder microvasculature disease a component of systemic atherosclerosis? Neurourol Urodyn, 37: 1372-1379, 2018.
• 17.   Kapoor H, Gupta E, Sood A. Chronic pelvic ischemia: etiology, pathogenesis, clinical presentation and management. Minerva Urol Nefrol, 66: 127-137, 2014.
• 18.   Akaihata H, Matsuoka K, Hata J, et al. Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2-Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat. Int J Mol Sci, 24: 3982, 2023.
• 19.   Akaihata H, Hata J, Tanji R, et al. Tetrahydrobiopterin prevents chronic ischemia-related lower urinary tract dysfunction through the maintenance of nitric oxide bioavailability. Sci Rep, 10: 19844, 2020.
• 20.   Akaihata H, Nomiya M, Hata J, et al. Pelvic arterial occlusive disease affects the RhoA/Rho-kinase pathway in bladder smooth muscle. J Urol, 193: 706-713, 2015.
• 21.   Koguchi T, Haga N, Matsuoka K, et al. Atherosclerosis as a predictor of transient exacerbation of overactive bladder symptoms after robot-assisted laparoscopic radical prostatectomy. 26: 234-240, 2019.
• 22.   Hennessey DB, Hoag N, Gani J. Impact of bladder dysfunction in the management of post radical prostatectomy stress urinary incontinence-a review. Transl Androl Urol, 6: S103-S111, 2017.