Stress Urinary Incontinence After Holmium Laser Enucleation of Prostate: Incidence and Risk Factors

Objectives: To evaluate the incidence and the risk factors of stress urinary incontinence (SUI) during the rst year after HoLEP. Patients and Methods: This study presents a monocentric and retrospective study including 155 patients who underwent HoLEP for benign prostatic hyperplasia. The surgeries were performed by 2 expert surgeons. The continence was evaluated at 1, 3, 6 and 12 months. The predictive factors of SUI were analysed by logistic regression. Results: The SUI rate at 1, 3 and 6 months was 11.3%, 10.7% and 4.1% respectively. SUI remained present in 4 patients (2.6%) at 12 months. The mean ICIQ-SF scores in patients with SUI were 10.3±6.09 and 8±4.24 at 1 and 12 months respectively (p <0.05). BMI>30 (OR, 4.69; 95% CI, 1.51–14.52; p=0.007) and patients over 70 years old (OR, 16.23; 95% CI, 1.96–134.09; p=0.010) were identied as independent risk factors for SUI at 1 and 3 months respectively.


Introduction
Transurethral resection of the prostate (TURP) and open prostatectomy (OP) still remains the 'gold standard' surgical treatment for symptomatic benign prostatic hyperplasia (BPH) resistant to medical treatment [1,2].
Currently, Holmium laser enucleation of the prostate (HoLEP) has become an important alternative treatment modality to TURP and OP [3]. This endoscopic approach enables a complete excision of the adenoma whatever its volume. Comparatively to TURP and OP, HoLEP improves patient recovery by reducing blood loss, urinary catheterisation duration and hospitalization length. Moreover, functional results are equivalent to conventional techniques [3,4].
Post-operative stress urinary incontinence (SUI) has been reported after HoLEP, with a negative in uence on the patient's quality of life (QoL) [5,6]. This complication can concern up to 16% of patients 3 months after surgery, but is most often transient [7].
From a technical point of view, the difference between TURP/OP and HoLEP is the direction of adenoma dissection. In a HoLEP procedure, dissection is carried out retrogradely through the urethral sphincter (transsphincter endoscopic enucleation). This method could induce sphincter lesion if the apical adenoma is improperly dissected [8]. Surgeons during their learning phase are especially prone to this mistake [5].
However, SUI has also been reported after HoLEP performed by experienced surgeons [9,10].
Several studies have identi ed peri operative urinary incontinence risk factors based on patient-reported data [10,11], but only a few have used validated urinary incontinence questionnaires in order to distinguish the different types of incontinence and their incidence [12,13].
The aim of this study was to evaluate the incidence of de novo stress urinary incontinence after HoLEP and to identify predicting risk factors.

Materials And Methods
A retrospective monocentric study was performed using observational data from all patients undergoing HoLEP for symptomatic BPH with no satisfactory response to medication therapy between May 2018 and December 2019. The procedure was carried out in patients with moderate to severe lower urinary tract symptoms and/or severe urinary retention and/ or other complications related to BPH. Patients with bladder or prostate cancer (except those on active surveillance), urethral stenosis, self catheterism, chronic renal failure or cognitive disorders, were excluded from the study. HoLEP procedures were conducted by 2 experts surgeons with an experience of more than 200 HoLEPs each one.

Surgical technique
Enucleation was performed according to the three-lobe technique described by Gilling [14] with early apical dissection using the white line technique to differentiate between apical adenoma and urethral sphincter. For enucleation, a reusable 1000 µ laser ber was inserted through a 24.5 Fr endoscope and the holmium generator was set to 100 W (2 J, 50 Hz). The Morscope Wolf Piranha ™ was used for morcellation of the adenoma.
Enucleation of the lobes was performed using the retrograde approach. The rst step was to prepare the bladder neck by making a T incision at 5 and 7 o'clock to avoid ureteral meatus injury during midlobe enucleation. The second step involved detaching each lateral lobe at the apex of the adenoma, starting with a super cial incision of the mucosa at low power (20 W) (white line technique). The posterior incision opposite the veru (hockey stick-shaped) joined a second anterior incision to form an inverted Y. Once released at the apex, the lateral lobe was gradually pushed back into the plane of the capsule by the ballistic action of the laser beam at 100 W. In order to limit potential effects of leverage on the sphincter, no mechanical push was applied to the endoscope.

Additional measures
Pelvic oor muscle training (PFMT) was systematically prescribed if SUI was reported by patients at the rst follow-up.

Assessment of voiding status and continence
Patients' pre-operative evaluation included IPSS, Qol-IPSS and ICIQ-SF questionnaires as well as a clinical and rectal examination, a ow measurement including post-void residual volume (PVR), an assessment of prostatic volume by trans-rectal ultrasound and a PSA test.
The post-operative evaluation was systematically carried out at 1, 3, 6 and 12 months. At each point of follow up, a ow measurement with PVR as well as IPSS, Qol-IPSS and ICIQ-SF questionnaires were collected. The number of daily urinary pads was also noted at each visit. The PSA test was performed at 3 and 12 months.

General data
Demographic data, perioperative data were collected in a standardized and retrospective manner from the computerized medical record of each patient.

Statistical analysis
Statistical analyses were performed with SPSS Statistics (IBM SPSS Statistics Version 20). To compare preand post-operative continence status, a nonparametric t test was used. The predictive factors for the occurrence of post-operative SUI were analysed by logistic regression. A P value of <0.05 was considered as statistically signi cant.

Ethics
This study was approved by the ethics committee of the Hospices Civils de Lyon and registered with the CNIL (Commission Nationale de l'Informatique et des Libertés) under number 18-127.

Results
One hundred and seventy-ve HoLEPs were carried out consecutively in our institution, of which 155 were assessed. (Figure 1) The demographic and perioperative data are set out in Table 1. Complete functional results at 1, 3, 6 and 12 months are reported in Table 1. The nature and severity of urinary leakage is detailed in Table 2. The rates of SUI de novo at 1, 3 and 6 months post-surgery were 11.3%, 10.7% and 4.1% respectively. Despite beginning bladder and sphincter rehabilitation in the rst postoperative month in all patients with urinary leakage, SUI persisted in 4 patients (2.6%) at 12 months. However, only 2 patients (1.3%) wore one pad per day at 12 months. The mean ICIQ-SF scores for patients with SUI were 11.69 ± 5.28, 8.70±4.24, 1.81±3.53 and 8 ± 4.24 at 1, 3, 6 and 12 months, respectively ( Table 2). In univariate and multivariate analysis, Body Mass Index (BMI) > 30 (OR, 4.69; 95% CI, 1.51-14.52; p = 0.007) was an independent risk factor for the occurrence of post-operative SUI at 1 month, whereas age > 70 years (OR, 16.23; 95% CI, 1.96-134.09; p = 0.010) was an independent risk factor for occurrence at 3 months (Table 3). At the time of the study, none of the patients presenting SUI required an implantable device.

Discussion
Transient stress urinary incontinence is a complication commonly reported after HoLEP. Its occurrence varies in the literature from 3.3 to 26% at 3 months (Table 4). Fortunately, most cases recover within the rst year [7]. explanation for the variation of reported SUI rates is the lack of a standard evaluation. Without the use of a validated questionnaire, incidence and prevalence of postoperative urinary incontinence could be underestimated, and precise determination of the type of incontinence is di cult [15]. The ICIQ-SF is a validated questionnaire in male urinary incontinence that distinguishes different types of urinary incontinence and estimates their severity [16]. The present study showed 11.4% and 10.5% de novo SUI at 1 month and 3 months respectively. The use of the same questionnaire at each follow up point con rmed the transient nature of SUI. Indeed, only 4 patients (2.6%) reported a persistent mild urinary leakage at one year despite PFMT.
Two main independent demographic risk factors for the occurrence of SUI during the rst 3 postoperative months were identi ed: age greater than 70 years (p <0.02) and a BMI greater than 30 (p <0.007). These results con rm those of Nam et al [7] who reported, in a retrospective series of 391 patients, a signi cantly higher rate of transient SUI in patients over 65 years old. In another retrospective and multicentric series of 2346 patients, increasing age and elevated BMI were also signi cantly associated with urinary incontinence [17]. Other demographic risk factors such as a history of diabetes mellitus and a pre-operative prostate volume greater than 81g have also been reported [17] but were not found in our study. Intrinsic sphincter insu ciency in elderly, overweight and diabetic patients could favour the occurrence of transient SUI after endoscopic enucleation [18].
In this study, we did not identify any intraoperative factor that could induce transient SUI. However, during HoLEP, some factors could cause an occlusion defect of the urethra-sphincter complex which leads to transient SUI: widening of the bladder neck, tearing of muscle bres due to excessive use of mechanical thrust, heat damage to muscle bres due to excessive use of laser energy at the apex of the adenoma, incomplete occlusion due to circumferential tearing of the proximal sphincter's mucosa (seal effect). Elmansy et al showed that a decrease in PSA level greater than 84%, re ecting the amount of removed prostate tissue, was associated with a higher risk of stress urinary incontinence [19]. Similarly, enucleation weight have been considered as an independent intraoperative predictive factor of urinary incontinence at 3 and 6 months [17].
In the same way, technical di culty like poor visibility of the operating eld due to excessive bleeding was linked to a higher risk of inappropriate endoscopic manipulations and thus urethral sphincter injury [7,19,20]. Several authors have also suggested that reducing the energy delivered during enucleation, in particular when near the urethral sphincter, could minimize the risk of thermal damage without increasing operating time [12]. Unfortunately, no consensus for the optimal setting has yet been reached.
Several HoLEP techniques have been reported since the rst procedure described by Gilling [14] : 2-lobes technique [21], En-Bloc technique [22], white line technique [23,24], anteroposterior dissection HoLEP [25], Top-Down HoLEP [26] . In a non-randomized retrospective monocentric study, Endo and al [25] reported a decrease of incontinence rate (2.7% vs 25.2%) in favour of anteroposterior dissection HoLEP versus Gilling's method. However, these results have not yet been con rmed. As described earlier, our technique is a mix of the white line and the 3-lobe techniques. Our modi cations based on early apex dissection avoid stretching the urethral sphincter by rst separating the adenoma from the sphincter area. Lateral lobe enucleation was carried out through the adenoma apex until reaching the capsule. Small apical adenomatous remnants were left in place as sphincter protective aps. With this method, only 2 patients (1.3%) reported a persistent mild stress urinary incontinence requiring one pad per day at one year. However, in the absence of comparative studies, it is impossible to identify one technique that would preserve continence more safely.
In our study, HoLEP was carried out by 2 operators which had conducted at least 200 HoLEP procedures. it is well known that the learning curve affects the incidence of SUI after HoLEP [7,11]. Fifty procedures at least are necessary to master the technique [26]. In this phase, the unassisted beginner surgeon is exposed to an increased risk of SUI by sphincter injury due to an inappropriate apex dissection [9,11,13] as well as an excessive operating time [27]. For these reasons, increased initial case density [11] and structured mentorship programs (video viewing, simulator training and active proctoring) are needed to improve the safety of HoLEP procedures [28]. Moreover, avoiding potentially complicated cases (prostate volumes greater than 80g, anticoagulated patients, patients with prostate cancer, prior prostatic radiotherapy) during the learning phase has been recommended [26].
The current study has several limitations, as a non-controlled study with a retrospective design and a small number of patients. In addition, there were no objective measurements, such as a pad test or a voiding diary.
Finally, urodynamic tests other than uro owmetry were not routinely performed. However, the use of the same surgical technique by two experienced operators in the same hospital and the systematic evaluation of postoperative urinary incontinence by a standardized and validated questionnaire, made it possible to reduce biases due to patients interview, learning curve and different practices.

Conclusion
In this study, we reported a low SUI rate one year after HoLEP. Transient SUI was more frequent in elderly and overweight patients. These results should be taken into consideration when informing patients about postoperative complications. We suggest that careful patient selection and appropriate preventive and therapeutic care (weight loss, PFMT) could be helpful in decreasing transitory SUI rate. Additional prospective and comparative studies on larger cohorts are needed to support these results.

Declarations
All methods were carried out in accordance with relevant guidelines and regulations Ethics approval and consent to participate: All Subjects have given their written informed consent The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Competing interests:
The authors have no competing interests to declare.

Fundings:
The authors received no speci c funding for this work.      Figure 1 Flow chart