DOI: https://doi.org/10.21203/rs.3.rs-31551/v2
Background: To evaluate the association between pre- and postoperative parameters on magnetic resonance imaging (MRI) and continence recovery after laparoscopic radical prostatectomy (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 defined as no pad per day. Early continence recovery was defined 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 after LRP.
Results: Patients with smaller prostatic volume, shorter intravesical prostatic protrusion length (IPPL), longer 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 after LRP.
Conclusion: IPPL, preoperative MUL, MUL-removal rate and shape of VUA were promising parameters on MRI for predicting continence recovery after LRP.
Radical prostatectomy (RP) is the main treatment option for localized prostate cancer, which obtains favorable oncological outcomes [1]. However, post-prostatectomy incontinence (PPI) is a bothersome complication with a significant negative effect on the health-related quality of life [2]. A systemic review showed that 4-31% of patients complain of urinary incontinence in 12 months after RP, with a “No Pad” definition of PPI [3].
Despite the etiology of PPI is multifactorial and complex, reduction of internal urethral pressure is the main factor. Several clinical parameters have been identified to be predictors of PPI, including age, body mass index (BMI), metabolic syndrome, prostate volume (PV), preoperative overactive bladder and neurovascular bundle (NVB) sparing [4-6]. Furthermore, urologists have proposed to predict continence recovery with preoperative anatomical parameters on magnetic resonance imaging (MRI) such as MUL and intravesical prostatic protrusion length (IPPL) [7,8]. However, the role of postoperative anatomical parameters in continence recovery has not been evaluated sufficiently. For better patient counseling and early intervention, it is important to identified the risk factors for PPI. The objective of the study was to evaluate the association between pre- and postoperative anatomical parameters on MRI and continence recovery after laparoscopic radical prostatectomy (LRP).
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. None of the patients had history of incontinence or urethral stricture. None of the 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. Urethro-vesical anastomosis was performed with 3-0 V-Loc sutures continuously.
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 (Fig 2a) was defined as the distance from the apex of prostate to the level of the urethra at penile bulb on the coronal image [7]. Postoperative MUL (Fig 2b) was defined as the distance from the bladder neck to the level of the urethra at the penile bulb on the coronal image. 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 classified into triangle and square (Fig 3a and 3b). PV, IPPL, pre- and postoperative MUL, and shape of VUA were evaluated by one senior urologist who were blinded to the clinical results.
Continence evaluation
We routinely instructed the patients of pelvic floor 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 defined as freedom from using safety pad (0 pad/day). Early continence recovery was defined as continence recovery within 3 months [9].
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. All tests of significance were two sided, and p < 0.05 was considered statistical significance.
The clinical and pathological characteristics of patients are summarized in Table 1. The mean age was 69.8±7.7 years. Patients with an mean BMI of 25.0±3.2 kg/m2. The mean operation time was 227±68 min, and the mean estimated blood loss was 106±123 ml. Non-, unilateral, and bilateral NVB sparing LRP was performed in 22 (30.1%), 4(5.5%) and 47(64.4%) patients, respectively. There were 5(6.8%), 27(40.0%) and 41(56.2%) patients with Gleason score 6, 7 and ≥8, respectively. 32(43.8%) patients suffered a positive surgical margin. The mean PV was 39.6 ± 22.3ml, the mean IPPL was 2.8 ± 4.6mm, the mean preoperative MUL was 13.1 ± 3.2mm and the mean MUL-removal rate was 6.0%. There were 50(68.5%) patients with triangle VUA, 23(31.5%) patients with square VUA on the postoperative MRI.
In the study 57.5% (42/73) of patients achieved early continence recovery after LRP. Continence recovery was achieved in 78.1% (57/73) and 97.3% (71/73) of patients within 6, and 12 months after LRP, respectively. Patients achieving early continence recovery had significant shorter operation time (210 min vs. 249 min, p = 0.024), less estimated blood loss (75 ml vs. 148 ml, p = 0.029), smaller PV (33.7 ml vs. 47.5ml, p = 0.008), shorter IPPL (0.9 mm vs. 5.4 mm, p < 0.001), longer preoperative MUL (14.3 mm vs. 11.6 mm, p < 0.001), lower MUL-removal rate (1.9% vs. 11.7%, p < 0.001), higher prevalence of triangle VUA (p < 0.001) and NVB sparing (p = 0.014) (Table 1). There was no significant difference between the two groups in age, BMI, PSA, and pathological characteristics such as Gleason score, pathological T stage and positive surgical margin (Table 1).
Kaplan-Meier analyses and log-rank test revealed that NVB sparing status (yes vs. no, p = 0.005), PV (<40ml vs. ≥40 ml, p = 0.001), IPPL (<5 mm vs. ≥5 mm, p = 0.001), preoperative MUL (≥15mm vs. <15mm, p < 0.001), MUL-removal rate (<10% vs. ≥10%, p < 0.001) and shape of VUA (square vs. triangle, p < 0.001) were all significantly associated with continence recovery (Supplemental Fig 1). Univariate Cox proportional analyses revealed NVB sparing status (p = 0.021), PV (p = 0.016), IPPL (p = 0.002), preoperative MUL (p = 0.004), MUL-removal rate (p < 0.001) and shape of VUA (p < 0.001) were predictors of continence recovery after LRP (Table 2). On the multivariate analyses, only IPPL (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.88-1.00, p = 0.044), preoperative MUL (HR: 1.10, 95% CI: 1.01-1.19, p = 0.032), MUL-removal rate (HR: 0.91, 95% CI: 0.86-0.98, p = 0.007) and shape of VUA (square vs. triangle, HR: 2.30, 95% CI: 1.21-4.39, p = 0.012) were identified to be independent predictors of continence recovery after LRP (Table 2).
Incontinence remains to be one of the most significant 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 significant difference on ages between patients with and without early continence recovery. Nyarangi‑Dix 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 confirmed to be an effective surgical technique for improving continence recovery [14,15]. Our study also revealed that patients treated with NVB sparing achieved significant better continence recovery.
We identified that preoperative MUL was an independent predictor of continence recovery. Coakley et al [16] firstly 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 significantly 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 identified to be an important predictor of continence recovery [20]. Kohjimoto et al [21] examined 179 prostate specimens of RP and identified that MUL removed with prostate was an independent predictor of continence recovery. Our study revealed that patients with higher MUL-removal rate suffered a significantly 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 identified to be predictors of continence recovery after RP [8,9]. Lee et al. [8] reported that significant 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 identified to be a powerful predictor of continence recovery [23]. Our previous study also confirmed that patients achieved early continence recovery after LRP had a significant shorter IPPL [24]. The core condition of urinary continence is the balance of detrusor contractility and urethral pressure. Intravesical prostatic protrusion was identified 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 revealed 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 fibrosis 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 insufficient urethral closure pressure. Haga et al [19] found that patients with triangle bladder neck had better urinary continence, but it failed to showed significant difference. Further research on the association between the shape of UVA and continence recovery after RP is necessary.
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, several surgeon and patient factors such as thermal dissection close to NVB, preoperative sphincter control are involved in continence recovery after RP.
Our study identified that IPPL, preoperative MUL, MUL-removal rate and shape of VUA were independently predictors of continence recovery after LRP. Parameters on pre- and postoperative MRI closely related with continence recovery. An MRI-based risk scoring system is needed to predict continence recovery after LRP.
MRI: magnetic resonance imaging; LRP: laparoscopic radical prostatectomy; IPPL: intravesical prostatic protrusion length; MUL: membranous urethral length; VUA: vesicourethral anastomosis; PPIS: Post-Prostatectomy Incontinence Score; RP: radical prostatectomy; PPI: post-prostatectomy incontinence; BMI: body mass index; PV: prostate volume; NVB: neurovascular bundle; AUC: area under the receiver operating characteristic curve.
Ethics approval and consent to participate
This study received institutional board approval at Peking University Third Hospital Medical Science Research Ethics Committee (IRB M2020235).
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 conflicts 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.
Acknowledgements
Not applicable
Table 1 Clinical and pathological characteristics of total patients and groups according to the early continence recovery after laparoscopic radical prostatectomy |
||||
Variables |
Total |
Early continence recovery |
P value |
|
Yes (n=42) |
No (n=31) |
|||
Age, mean ± SD (years) |
69.8±7.7 |
68.8±7.8 |
71.1±7.6 |
0.210 |
BMI, mean ± SD (kg/m2) |
25.0±3.2 |
24.8±2.6 |
25.2±3.9 |
0.577 |
PSA, mean ± SD (μg/L) |
25.5±41.6 |
19.0±28.6 |
34.3±53.8 |
0.159 |
Operation time, mean ± SD (min) |
227±68 |
210±52 |
249±81 |
0.024 |
Estimated blood loss, mean ± SD (ml) |
106±123 |
75±51 |
148±172 |
0.029 |
Gleason score |
0.406 |
|||
6 |
5 (6.8) |
2 |
3 |
|
7 |
27 (40.0) |
18 |
9 |
|
≥8 |
41 (56.2) |
22 |
19 |
|
Pathological stage |
0.736 |
|||
T2 |
37 (50.7) |
22 |
15 |
|
≥T3 |
36 (49.3) |
20 |
16 |
|
Positive surgical margin |
0.250 |
|||
No |
41 (56.2) |
26 |
15 |
|
Yes |
32 (43.8) |
16 |
16 |
|
NVB sparing status |
0.014 |
|||
No |
22 (30.1) |
7 |
15 |
|
Unilateral |
4 (5.5) |
3 |
1 |
|
Bilateral |
47 (64.4) |
32 |
15 |
|
PV, mean ± SD (ml) |
39.6±22.3 |
33.7±17.7 |
47.5±25.6 |
0.008 |
IPPL, mean ± SD (mm) |
2.8±4.6 |
0.9±2.1 |
5.4±5.8 |
<0.001 |
preoperative MUL, mean ± SD (mm) |
13.1±3.2 |
14.3±2.7 |
11.6±3.3 |
<0.001 |
postoperative MUL, mean ± SD (mm) |
12.4±3.3 |
14.0±2.6 |
10.1±2.9 |
<0.001 |
MUL-removal rate, (%) |
6.0±6.2 |
1.9±3.7 |
11.7±4.0 |
<0.001 |
Shape of VUA |
<0.001 |
|||
Triangle |
50 (68.5) |
38 |
12 |
|
Square |
23 (31.5) |
4 |
19 |
|
SD, standard deviation; BMI, body mass index; LUST, lower urinary symptom; PSA, prostate specific antigen; PV, prostatic volume; IPPL, intravesical prostatic protrusion length; MUL, membranous urethral length; NVB, neurovascular bundle; VUA, vesicourethral anastomosis |
Table 2. Univariate and multivariate analysis of parameters predicting continence recovery after laparoscopic radical prostatectomy. |
|||
Variables |
Univariate |
Multivariate |
|
P value |
HR (95% CI) |
P value |
|
Age (years) |
0.186 |
||
BMI (kg/m2) |
0.331 |
||
Operation time (min) |
0.229 |
||
Estimated blood loss (ml) |
0.108 |
||
NVB sparing status (Yes vs. No) |
0.021 |
0.74 (0.43-1.30) |
0.297 |
PV (ml) |
0.016 |
1.00 (0.99-1.01) |
0.991 |
IPPL (mm) |
0.002 |
0.94 (0.88-1.00) |
0.044 |
Preoperative MUL (mm) |
0.004 |
1.10 (1.01-1.19) |
0.032 |
MUL-removal rate (%) |
<0.001 |
0.91 (0.86-0.98) |
0.007 |
Shape of VUA (square vs. triangle) |
<0.001 |
2.30 (1.21-4.39) |
0.012 |
BMI, body mass index; NVB, neurovascular bundle; PV, prostatic volume; IPPL, intravesical prostatic protrusion length; MUL, membranous urethral length; VUA, vesicourethral anastomosis. |
Table 3 The scoring criteria of Post-Prostatectomy Incontinence score (PPIS) |
||
PPIS |
0 score |
1 score |
Intravesical prostatic protrusion length (mm) |
<5 mm |
≥5 mm |
Preoperative membranous urethral length (mm) |
≥15mm |
<15mm |
Membranous urethral length-removal rate |
<10% |
≥10% |
Shape of vesicourethral anastomosis |
Triangle |
Square |