Early recovery of urinary continence after robot‐assisted radical prostatectomy is associated with membranous urethra and neurovascular bundle preservation

We investigated the correlation between surgical outcomes and postoperative urinary continence recovery in robot‐assisted radical prostatectomy (RARP).


INTRODUCTION
In 2018, 92 021 men in Japan developed prostate cancer, the highest among all carcinomas 1 and the sixth highest cause of cancer deaths in Japan in 2020 (12 759 deaths). 2 A common treatment for localized and locally advanced prostate cancer is robot-assisted radical prostatectomy (RARP).However, after surgery, urinary incontinence can persist and reduce quality of life by affecting physical activity, social relationships, emotional health, ability to travel, anxiety levels, and depression. 3Therefore, urinary incontinence after RARP is a serious concern.
Factors associated with postoperative incontinence include patient selection, pre-and postoperative membranous urethral length (MUL), and intraoperative procedures affecting the cavernous nerve of the penis, fascia, and ligaments.In addition, the postoperative duration of urinary catheter placement has been mentioned as associated with postoperative incontinence in previous reports. 4Further, a study revealed that sympathetic, sensory, and nitrergic nerves are distributed in the internal and external urethral sphincter along with autonomic fibers within the neurovascular bundles (NVBs). 5The authors concluded that during radical prostatectomy, the NVBs should be preserved. 5Although various factors may affect postoperative urinary incontinence, a definitive factor has not been determined.
In our previous study, preserved urethral length (PUL) after RARP was found to correlate significantly with postoperative urinary continence recovery rate. 6In this study, we measured the PUL quantitatively during RARP and investigated the association of both PUL and NVB preservation with postoperative urinary continence recovery.

PATIENTS AND METHODS
This study was approved by our institute's institutional review board (IRB) (IRB number: A19-199).Patients who underwent RARP for prostate cancer at our institution between May 2020 and March 2022 were enrolled in the study.
Patient characteristics, perioperative outcomes, and pathological findings, including age, body mass index (BMI), preoperative prostate-specific antigen (PSA), date of surgery, presence of urinary continence after RARP, number of days to achieve urinary continence, date of the last consultation, total operative time, console time, loss of blood volume, weight of the resected prostate, pathological T stage, surgical margin status, and follow-up periods, were obtained from medical records, as described previously. 6Continence recovery was indicated when social continence was attained (use of a small 20-mL pad required daily), as described previously. 6On postoperative day 6, urethral catheters were removed, and patients were instructed to perform pelvic floor exercises postoperatively.
Operative records and case summaries revealed surgical skill outcomes, such as preservation of NVBs, the puboprostatic ligament, endopelvic fascia, and PUL.

Surgical techniques of RARP
Transperitoneal RARP with six ports was performed, as described previously. 6Magnetic resonance imaging (MRI) findings and the positive prostate biopsy site indicated the sparing side for the NVB.Bilateral NVB were spared when the positive prostate biopsy site was in the transition zone.The PUL was measured using a ruler intracorporeally prior to incision of the urethra, with the prostate pulled superiorly (Figure 1).Only posterior reconstruction was performed.RARP was performed by 9 surgeons as an operator.One surgeon (T.F.) also participated in all of the procedures as an instructive assistant.

Statistical analyses
Continuous data were subjected to the Wilcoxon rank sum test, while the Chi-squared test was used for categorical data.Continence recovery rate curves were plotted.We used the Kaplan-Meier method to plot continence recovery rate curves, with comparisons using the log-rank test.The correlation between clinical parameters and continence recovery was examined using univariate and multivariate Cox proportional hazards models, with median values used to determine cutoffs for age, BMI, and resected prostatic volume.The cut-off value for PUL was determined by receiver operating characteristic (ROC) curves.All statistical analyses were performed using the JMP Pro version 16.0.0software (SAS Institute Inc., Cary, NC, USA), with a p-value of 0.05 considered to represent a significant difference.

RESULTS
Characteristics and perioperative findings of the 195 patients enrolled in the study are summarized in Table 1.Of these patients, 21, 107, and 67 patients had bilateral, unilateral, and non-NVB-sparing operations, respectively, and 147, 29, and 19 patients had bilateral, unilateral, and non-fascia-sparing operations, respectively.In addition, 156, 28, and 11 patients had bilateral, unilateral, and non-puboprostatic ligamentsparing operations, respectively.The median PUL was 27 mm.The median postoperative follow-up period was 381 days (interquartile range, 292-528 days).Table 2 shows a summary of oncological data and postoperative recurrence.An ROC curve determined the cut-off value for PUL as 26 mm (Figure S1).
Age, BMI, NVB preservation, endopelvic fascia preservation, puboprostatic ligament preservation, PUL, and resected prostatic volume were examined in univariate and multivariate analyses using the Cox proportional hazards model.Among all patients, no significant difference in postoperative urinary continence recovery at 30, 60, 90, and 365 days after RARP was observed.Univariate and multivariate analyses of NVB preservation, endopelvic fascia preservation, puboprostatic ligament preservation, and PUL at 30 days after RARP were not evaluated as no events occurred (Table 3).
Kaplan-Meier curves for cumulative urinary continence rates showed significantly better recovery of urinary continence within 30 postoperative days in patients with a PUL ≥26 mm than in those with a PUL <26 mm (Figure 2a) and in patients with NVB preservation than in patients without NVB preservation (Figure 2b).However, significantly better urinary continence recovery within 30, 60, 90, and 365 postoperative days was observed in patients with a PUL ≥26 mm and NVB preservation than in patients without a PUL ≥26 mm or NVB preservation (Log-rank test: p < 0.0001, p = 0.016, p = 0.020, p = 0.013, respectively) (Figure 3; Figure S6).The 1-year urinary continence recovery rate after surgery was 87.3% for patients with a PUL ≥26 mm, 76.5% for patients with a PUL <26 mm, 86.1% for patients with NVB preservation, 84.4% for patients without NVB preservation, 90.6% for patients with a PUL ≥26 mm and NVB preservation, and 82.3% for patients with a PUL <26 mm or no NVB preservation (Figure 3; Figures S4 and S5).There was no significant difference between bilateral NVB preservation and unilateral NVB preservation in continence recovery rate (Figure S2).Among the cohort that does not include bilateral NVB preservation, there was no significant difference between the group with a PUL of ≥26 mm with unilateral NVB preservation and the other groups in continence recovery rate (Figure S3).

DISCUSSION
In this study, we found that patients with a PUL ≥26 mm and NVB preservation had significantly better urinary continence recovery rates at 30, 60, 90, and 365 days postoperatively compared with patients with a PUL <26 mm or no NVB preservation.Although there have been some studies in the past in which NVB preservation alone or urethral preservation alone significantly improved early postoperative continence, none of those studies showed significantly better continence recovery rates after 1 year.Our results suggest that preserving both the urethra and the NVB is important in achieving urinary continence recovery.
In the patient group in the current study, all patients had a median PUL of 27 mm because the urethra was preserved to be as long as possible.The median PUL in the previous study was 10.6 mm. 6Although direct comparisons cannot be made because the measurement methods used in the current study were quantitative and those used in the previous study were semi-quantitative, having a longer PUL requires actively preserving the urethra.][9][10][11][12][13] However, even if the native membranous urethra is considered long on MRI, surgical procedures may not be able to preserve the membranous urethra length.Therefore, we considered it more important to preserve a longer urethra during the procedure than to have a longer preoperative native MUL.Our previous study measured the PUL in RARP semiquantitatively.The study showed that patients with a PUL ≥16 mm had a significantly higher rate of recovery from urinary incontinence during the overall observation period. 6In that previous study, the PUL varied greatly from one case to another.In another study, maximal preservation of the membranous urethra improved the continence recovery rate. 10Although not investigated in the present study, MUL measured on cystourethrography images at the time of removal of the postoperative balloon catheter has been reported to be the most important factor in the recovery of postoperative continence after RARP, 14,15 consistent with our findings.Preservation of the cavernous nerve of the penis has been reported as important not only to preserve male sexual function, but also in the postoperative recovery of urinary continence.Bilateral cavernous nerve preservation is associated with increased incidence of early postoperative continence recovery after radical prostatectomy compared to unilateral nerve preservation. 16However, rather than nerve preservation itself, a reduction in thermal injury, increased preservation of tissue around the urethra and pelvic floor during nerve sparing, and meticulous apical dissection may improve urinary continence recovery. 16,17Autonomic nerves from the inferior hypogastric plexus innervate the external and internal urethral sphincter and some of these autonomic fibers run within the NVBs posterolaterally, as revealed by immunohistochemistry of en bloc excised specimens of the fetal pelvis. 5In addition, neuroanatomical studies suggest that NVB preservation may contribute to the preservation of the autonomic nerves to the urethral sphincter, thus, improving urinary continence recovery.
When attempting to extend the PUL, attention should be paid to preventing positive surgical margins (PSMs).We compared the PSM rate in pT2 cases to our previous study and other studies.The PSM rate in patients with pT2 or less was 16.9% for all patients, 16.5% for patients with a PUL <26 mm, and 17.3% for patients with a PUL ≥26 mm at our institution.In our previous study, the PSM rate in patients with pT2 or less was 25.0% for all patients, 26.3% for patients with a PUL <16 mm, and 19.4% for patients with a PUL ≥16 mm.Thus, the PSM rate was lower in this study compared with that in our previous study.Preservation of the membranous urethra as much as possible did not increase the PSM.Other studies reported a median PSM rate of 19.0% (range, 4.7%-23.2%)with RARP in patients with pT2 or less, [18][19][20][21][22][23] suggesting that preserving the urethra was unlikely to affect PSM.However, if a preoperative MRI of the prostate, prostate needle biopsy, or digital rectal examination suggests the presence of a tumor at the apex of the prostate, attention should be paid to avoid PSM.Although data are not shown, this study includes cases of PSM located far from the apex of the prostate, which should be kept in mind when considering the PSM rate.
Many surgical techniques have been reported for achieving urinary continence after surgery.Our institution is also an educational institution for residents, and it is necessary to achieve both improvements in treatment outcomes and reduction of complications, as well as training new surgeons.An effective surgical procedure that both new and experienced surgeons can perform and that can achieve urinary continence is required.In this study, nine surgeons, including residents, performed the RARP as an operator, and, based on the cases, showed an excellent recovery rate from urinary incontinence.We believe that our surgical method is "universally designed surgery," which can achieve an excellent recovery rate from urinary incontinence regardless of the surgeon's previous surgical experience.
Our study has several limitations.First, there are limitations inherent to the limited sample size, and performing a prospective randomized study on the advantages and   FIGURE 3 (a) Urinary continence recovery rate curves stratified by preserved urethral length (PUL) and neurovascular bundle (NVB) preservation at 365 days after robot-assisted radical prostatectomy was plotted using the Kaplan-Meier method.A PUL ≥26 mm and NVB preservation were statistically significant factors that influenced urinary continence recovery at 365 days after robot-assisted radical prostatectomy (RARP) (p < 0.013).(b) Urinary continence recovery rate curves stratified by PUL and/or NVB preservation at 365 days after RARP was plotted using the Kaplan-Meier method.Although there were no significant differences among the four groups, a PUL ≥26 mm and NVB preservation tended to have better urinary continence recovery rates than the other three groups (p = 0.094).
disadvantages of PUL is difficult ethically.Second, this study was conducted at a single-center, and external validation using another data set is needed.Third, the force of cephalad retraction of the prostate with a third robotic arm may result in PUL measurement error.Finally, the influence of postsurgical pelvic floor training cannot be excluded.
Our results suggest that a significantly higher postoperative urinary continence recovery rate can be achieved in patients with a PUL ≥26 mm and NVB preservation after RARP.

FIGURE 1
FIGURE 1 Measurement of the preserved urethral length (PUL).The white arrow indicates urethral length.In this example, the PUL is 28 mm.The yellow arrows indicate the urethra.

FIGURE 2
FIGURE 2 (a) Continence recovery rate curves stratified by preserved urethral length (PUL) at postoperative day 30 were plotted using the Kaplan-Meier method.A PUL ≥26 mm was a statistically significant factor that influenced urinary continence recovery at 30 days after robot-assisted radical prostatectomy (RARP) (p = 0.0028).(b) Continence recovery rate curves stratified by neurovascular bundle (NVB) preservation at postoperative day 30 were plotted using the Kaplan-Meier method.NVB preservation was a statistically significant factor that influenced urinary continence recovery at 30 days after RARP (p = 0.014).

TABLE 1
Characteristics and perioperative parameters of the patients.

TABLE 2
Pathological findings and postoperative recurrence.International Society of Urological Pathology; NVB, neurovascular bundle; PUL, preserved urethral length.© 2024 The Authors.International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.