Pre- and Postoperative Parameters on Magnetic Resonance Imaging Predict Continence Recovery after Laparoscopic Radical prostatectomy

Background: To evaluate the association between pre- and postoperative parameters on magnetic resonance imaging (MRI) and continence recovery after laparoscopic radical prostatectomy (LRP). To develop a risk scoring system for predicting continence recovery after LRP. Methods: 73 patients who underwent LRP were retrospectively reviewed. Demographic characteristics, clinicopathologic outcomes and several MRI parameters before and after surgery were evaluated. Continence was dened as no pad per day. Early continence recovery was dened as continence recovery within 3 months. Kaplan-Meier analyses and log-rank test were used to compare time to continence recovery. Cox proportional-hazards regression analyses were performed to identify independent predictors of continence recovery. Results: Patients with smaller prostatic volume, shorter intravesical prostatic protrusion length (IPPL), shorter preoperative membranous urethral length (MUL), lower MUL-removal rate, triangular vesicourethral anastomosis (VUA) and neurovascular bundle sparing experienced a faster continence recovery (All, p < 0.05). Multivariate analyses revealed IPPL (hazard ratio [HR]: 0.94, p = 0.044), preoperative MUL (HR: 1.10, p = 0.032), MUL-removal rate (HR: 0.91, p = 0.007) and shape of VUA (square vs. triangle, HR: 2.30, p = 0.012) were independent predictors of continence recovery. The four parameters were therefore used to develop a risk scoring system, termed Post-Prostatectomy Incontinence Score (PPIS) and ranging from 0 to 4. We observed early continence recovery in 100%, 84.6%, 27.8%, 0% and 0% of patients with a PPIS of 0, 1, 2, 3, 4, respectively. Conclusion: IPPL, preoperative MUL, MUL-removal rate and shape of VUA were independently predictors of continence recovery. PPIS could accurately predict the early continence recovery after LRP.

evaluate the association between pre-and postoperative anatomical parameters on MRI and continence recovery after laparoscopic radical prostatectomy (LRP), and to develop a risk scoring system to predict the early continence recovery.

Study population
The retrospective study was conducted in 74 patients treated with LRP for localized prostate cancer at our institute from January 2015 to April 2019 and was approved by the Institutional Review Board of Peking University Third Hospital. All patients underwent pre-and postoperative MRI to evaluate the pelvic anatomical parameters. None of the patients had underwent transurethral resection or holmium laser enucleation of the prostate. No patients had history of incontinence or urethral stricture. No patients received neoadjuvant hormone therapy or radiotherapy. The clinical and pathological data was reviewed in our collected database.

Surgical procedures
All patients received extraperitoneal LRP. After cutting part of the puboprostatic ligament, the deep dorsal vein was suture-ligated. NVB-sparing procedure was attempted to perform for all clinical localized prostate cancer. Reconstruction was performed using full-thickness interrupted sutures when needed.

MRI parameters measurement
MRI was performed on a 3.0 Tesla magnetic resonance scanner. The mean interval from LRP to postoperative MRI was 12.9±7.0months. Parameters measurement was performed on T2-weighted MRI images. PV was calculated by the formula, i.e. PV = 0.52*length* width*height. IPPL was measured as the vertical distance from the tip of the protruding prostate to the base of the urinary bladder on the midsagittal image (Fig 1).. Preoperative MUL was de ned as the distance from the apex of prostate to the level of the urethra at penile bulb on the coronal image (Fig 2a).. Postoperative MUL was de ned as the distance from the bladder neck to the level of the urethra at the penile bulb on the coronal image (Fig 2b).. MUL-removal rate was calculated by the formula, i.e. MUL-removal rate = (Preoperative MUL -Postoperative MUL) / Preoperative MUL. The shape of vesicourethral anastomosis (VUA) on the midsagittal image was classi ed into triangle and square (Fig 3a and 3b).. PV, IPPL, pre-and postoperative MUL, and shape of VUA were evaluated by one observer who were blinded to the clinical results.

Continence evaluation
We routinely instructed the patients of pelvic oor muscle exercises to acquire the continence recovery after surgery. They were followed up by outpatient service or telephone interviews every 3 months. In the study, urinary continence was de ned as freedom from using safety pad (0 pad/day). Early continence recovery was de ned as continence recovery within 3 months.

Statistical analyses
All statistical analyses were conducted with SPSS statistics version 22.0 (IBM Corp, Armonk, NY, USA). Continuous variables were presented as the mean value and standard deviation. The comparison between discontinuous variables and continuous variables was evaluated by Chi-square test and Student's t test, respectively. Kaplan-Meier analyses and log-rank test were used to compare time to continence recovery between groups. Univariate and multivariate Cox proportional-hazards regression analyses were used to identify independent predictors of continence recovery after LRP. A risk scoring system based on the independent predictors was developed to classi ed patients according to the likelihood of the continence recovery, and the area under the receiver operating characteristic curve (AUC) on continence recovery was evaluated. All tests of signi cance were two sided, and p < 0.05 was considered statistical signi cance.

Discussion
Incontinence remains to be one of the most signi cant factors affecting quality of life after RP. In the present study, 57.5% of patients achieved early continence recovery, which was consistent with previous studies [4,9]. With the advances in knowledge of urinary continence mechanism, the main structure in continence is considered the external striated sphincter, which maintains a urethral closure pressure greater than bladder pressure. Sphincteric incompetence after RP may be a result of shorter MUL, loss of neural innervations, muscle damage and loss of the surrounding support tissue [10]. Though PPI is usually a temporary symptom, the lack of information predicting continence recovery leads to anxiety in patients and prevents early treatment for PPI. Therefore, to identify possible predictors of PPI and develop a risk scoring system can contribute to patient counseling and early intervention of PPI.
Advanced age has been proposed as an important predictor of continence recovery after surgery by some studies [4,11,12]. In contrast, our study revealed that there was not signi cant difference on ages between patients with and without early continence recovery. NyarangiDix et al [13] suggested that continence recovery in elderly men does not differ from younger men undergoing robot-assisted radical prostatectomy. Patient characteristics, surgeon experience and surgical techniques play an important role in continence recovery after RP. NVB sparing was con rmed to be an effective surgical technique for improving continence recovery [14,15]. Our study also revealed that patients treated with NVB sparing achieved signi cant better continence recovery.
We identi ed that preoperative MUL was an independent predictor of continence recovery. Coakley et al [16] rstly revealed that longer preoperative MUL was associated with faster continence recovery. The study reported 89% of patients with a MUL > 12 mm achieved continence recovery compared with 77% of patients with a preoperative MUL ≤ 12 mm in 12 months after surgery. A meta-analysis containing one randomized controlled trial and 12 cohort studies demonstrated that a longer preoperative MUL is signi cantly and positively associated with continence recovery after RP [17]. Matsushita et al [18] reported that the addition of preoperative MUL increased the AUC of model for predicting continence recovery, but the AUC was not good enough. Longer MUL including a greater amount of external striated sphincter, play an important role in maintaining and increasing the urethral closure pressures.
RP leads to damages in the structure and function of membranous urethra. However, the MUL-removal rates can vary greatly between different patients and surgeons. The postoperative MUL may be a more accurate parameter for predicting continence recovery than preoperative MUL. Since MRI is not routine performed after RP, only a few studies revealed that longer postoperative MUL was associated with a faster continence recovery after PR [7,9,19]. Postoperative MUL measured on cystourethrography was also identi ed to be an important predictor of continence recovery [20]. Kohjimoto et al [21] examined 179 prostate specimens of RP and identi ed that MUL removed with prostate was an independent predictor of continence recovery. Our study revealed that patients with higher MUL-removal rate suffered a signi cantly longer period of PPI. Therefore, blunt dissection of the urethra distal to the prostatic apex should be carried out for sparing the membranous urethra, which could contribute to improving continence recovery after RP [22].
In recent studies, several MRI parameters such as IPPL, bladder neck width were identi ed to be predictors of continence recovery after RP [8,9]. Lee et al. [8] reported that signi cant improvement in continence recovery was observed in patients with IPPL < 5 mm at all periods compared with those with IPPL ≥ 5 mm. In a cohort of 821 patients who underwent robot-assisted radical prostatectomy, IPPL measured by transrectal ultrasound was also identi ed to be a powerful predictor of continence recovery [23]. Our previous study also con rmed that patients achieved early continence recovery after LRP had a signi cant shorter IPPL [24]. The core condition of urinary continence is the balance of detrusor contractility and urethral pressure. Intravesical prostatic protrusion was identi ed to be associated with lower urinary tract symptoms and overactive bladder [25,26]. It is supposed that longer IPPL contributes to pathophysiological changes of bladder detrusor such as detrusor hyperactive, detrusor instability and subsequent bladder dysfunction, and then leads to a delay in continence recovery after RP. Furthermore, the impact of intravesical prostatic protrusion on more surgical damage of the internal sphincter during bladder neck dissections put forward as a possible contributor [25]. However, the underlying mechanisms by which IPPL affects continence recovery after RP remains unclear.
On the other hand, we reveled that square UVA was a strongly negative predictor of continence recovery after RP. The risk of PPI for patients with square UVA was 2.3 times higher than those with triangle UVA. However, the mechanisms resulting in the difference on the shape of UVA is unclear. It may be related to the procedure of dissociation proximal urethra and vesical-urethral anastomosis. We proposed that patient with square UVA may suffered more damage such as scarring and brosis to the membranous urethra, which may be caused by high tension anastomosis, subsequent tissue ischemia and mechanical damage to sphincter [27]. Compared to the triangle UVA, square UVA may be an important signal of insu cient urethral closure pressure. Haga et al [19] found that patients with triangle bladder neck had better urinary continence, but it failed to showed signi cant difference. Further research on the association between the shape of UVA and continence recovery after RP is necessary. Finally, we develop the PPIS with the independent predictors of continence recovery after LRP in our study. It presented a satis ed ROC for predicting continence recovery after LRP. To the best of our knowledge, PPIS is the rst risk scoring system based on pre-and postoperative MRI for predicting continence recovery after LRP. And the external validation studies are needed to be carried out.
The present study has some limitations. The retrospective nature of the study and the selection of patients with postoperative MRI could have generated unanticipated biases. The postoperative MRIs were performed in different intervals after surgery, which may affect the urethral parameters. Furthermore, the present study included a relatively small number of patients. Finally, the surgeon experience was not adjusted which may affect continence recovery after RP.

Conclusion
Our study identi ed that IPPL, preoperative MUL, MUL-removal rate and shape of VUA were independently predictors of continence recovery after LRP. PPIS is an MRI-based risk scoring system, which could accurately predict the continence recovery after LRP. The use of PPIS can help urologists to stratify patients who underwent LRP into subgroups with different risks of PPI.

Consent for publication
The manuscript is approved by all authors for publication.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests
All authors declare no potential con icts of interest.

Funding
Not applicable.
Authors' Contributions LLM, YH (Yi Huang) and FZ proposed the protocol. BY, FZ, YCH (Yichang Hao) and YY contributed to data collection and management. BY contributed to data analysis and statistical analysis. BY and FZ contributed to manuscript writing. LLM and YH (Yi Huang) revised the manuscript. All authors have read and approved the manuscript.   The vertical distance from the tip of the protruding prostate to the base of the urinary bladder on the midsagittal image de ned as intravesical prostatic protrusion length (IPPL).