Predictive factors of stress urinary incontinence after Holmium Laser Enucleation of the Prostate: a magnetic resonance imaging-based retrospective study

Introduction

Holmium Laser Enucleation of the Prostate (HoLEP) has been established as an efficacious intervention for ameliorating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) (1-3), outperforming transurethral resection of the prostate (TURP) in terms of diminished catheterization duration, reduced hemorrhage (4). Yet, postoperative stress urinary incontinence (SUI), which is transient can disappear over a while, remains a prevalent complication, manifesting in 14.5% of patients at three months, diminishing to 4.2% at 6 months (5), thereby substantially impacting quality of life. SUI after HoLEP is associated with external urethral sphincter injuries, such as intraoperative pulling and squeezing of the cystoscopic sheath on the external sphincter or thermal damage to the sphincter from holmium lasers; the dysfunction caused by these injuries is usually temporary (6,7). Identified predictors of postoperative SUI include age, obesity, frailty, prostate volume (PV), enucleated volume, and operative duration (5,8-11). Yet, the role of anatomical variables related to the lower urinary tract in SUI post-HoLEP is underexplored. This study seeks to bridge this knowledge gap by assessing the relationship between preoperative multiparametric magnetic resonance imaging (mpMRI)-determined anatomical factors and postoperative SUI. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-24-71/rc)

Methods

Study population

In this retrospective inquiry, we evaluated 402 cases of BPH managed via HoLEP (2-lobe-enucleation technique) by a consistent surgical practitioner (who has completed thousands of HoLEPs prior to this study) at Sun Yat-sen Memorial Hospital within the period of January 2021 to September 2022. Criteria for inclusion included: (I) individuals having undergone HoLEP at the designated facility; and (II) completion of preoperative prostate mpMRI. Exclusion criteria incorporated: (I) histopathological indication of prostate carcinoma; (II) documented preoperative urinary incontinence; (III) a history of transurethral surgeries; (IV) inability to participate in subsequent follow-ups; and (V) evidence of non-SUI urinary dysfunction postoperatively (including urge urinary incontinence, mixed urinary incontinence, etc.). Anatomical parameters including the posterior wall of the membranous urethral sphincter (TPWMUS), membranous urethral length (MUL), membranous urethral volume (MUV), and prostatic apex configuration were meticulously quantified by preoperative prostate mpMRI by an imaging specialist in the radiology department. We reviewed previous related studies and found that these anatomical parameters may be associated with SUI after HoLEP. These parameters were decided by the corresponding author after discussion in our group. This study was conducted in accordance with the Declaration of Helsinki (revised in 2013). Patient data were retrospectively reviewed without the need for informed consent. Since the study did not collect or record personally identifiable information, and used only simple contact measuring equipment or observation equipment that did not induce physical changes, it does not require ethical approval.

Follow-up protocol

Follow-up assessments utilized the International Consultation on Incontinence Questionnaire-Short Form for evaluating urinary incontinence. These evaluations were consistently conducted by a single clinician during outpatient visits.

Imaging and measurements

mpMRI was performed employing a 3.0 Tesla MR system (Achieva TX, Philips Healthcare, Best, Netherlands) with a 32-channel head coil. Measurements of TPWMUS and MUL were conducted on sagittal T2-weighted images, in alignment with established methodologies (12). MUL was gauged from the apical extent of the prostate to the inferior boundary of the urogenital diaphragm. Cross-sectional T2-weighted imaging facilitated the determination of TPWMUS by measuring the maximal extent of the membranous urethral sphincter’s posterior wall, see Figure 1.

Figure 1 TPWMUS, MUL. P, prostate; M, membranous urethral length; D, the longest diameter of membranous urethra; T, thickness of the posterior wall of membranous urethral sphincter; TPWMUS, thickness of the posterior wall of membranous urethral sphincter; MUL, membranous urethral length.

Prostatic apex morphology was categorized into four distinct types based on its spatial relationship to the membranous urethra, as visualized on magnetic resonance imaging (MRI). See Figure 2, where we categorized type ABC as the prostatic apex overlapping the membranous urethra (PAOMU) and type D as the prostatic apex not overlapping the membranous urethra (PANOMU). The volumetric measurement of the membranous urethra was computed via the formula: MUV = π × MUL × (D/2)², with ‘D’ representing the maximum diameter discerned on cross-sectional T2-weighted imaging. The anatomical landmarks were calculated by an imaging specialist in the radiology department, who was blinded to the patients’ outcomes. Therefore, the effect of imaging experience on the results is negligible.

Figure 2 PANOMU (A-C) and PAOMU (D). A, anterior membranous urethral sphincter; P, posterior membranous urethral sphincter; PAOMU, prostatic apex overlapping the membranous urethra; PANOMU, prostatic apex not overlapping the membranous urethra.

Statistical analysis

SPSS software version 26.0 (SPSS Inc., Chicago, Illinois, USA) was utilized for data analysis. Normally distributed data were expressed as means ± standard deviation (SD), while non-parametric data were presented as medians with ranges. Binary logistic regression was employed to elucidate risk factors correlated with postoperative SUI, with a P value of less than 0.05 considered indicative of statistical significance.

Results

The main outcome is the incidence of SUI after one month of HoLEP. A total of 216 patients met the inclusion criteria for this study, with 186 cases being excluded (78 cases’ preoperative prostate mpMRI were not completed; 34 cases had a history of transurethral surgeries; 26 cases had documented preoperative urinary incontinence; 5 cases had histopathological indication of prostate carcinoma; 43 cases had inability to participate in subsequent follow-ups; 3 cases had evidence of non-SUI urinary dysfunction postoperatively: 2 cases of urge incontinence and 1 case of mixed incontinence), among which 45 (20.83%) experienced SUI subsequent to one month of HoLEP therapy. At three months, 23 individuals exhibited recovery, reducing the prevalence of SUI to 10.19%. By the 6-month milestone, the incidence further declined to 1.38%, with 19 patients reporting normalization of continence. We use a flowchart to present the research process, see Figure 3. Subjects were grouped based on the presence of SUI at the one-month juncture, forming a non-SUI cohort and an alternative group comprising SUI-afflicted patients. Comparative analysis of normally distributed variables was executed using the Student’s t-test, whereas the Mann-Whitney U-test was applied for non-normally distributed data. Significant disparities were noted in MUL, MUV, and TPWMUS (Table 1).

Figure 3 Flowchart. HoLEP, Holmium Laser Enucleation of the Prostate; SUI, stress urinary incontinence; BPH, benign prostatic hyperplasia; mpMRI, multiparametric magnetic resonance imaging.

Employing median values of MUL, MUV, and TPWMUS for stratification purposes revealed that individuals with MUL <1.4 mm, MUV <1.6 cm³, and PAOMU exhibited a heightened likelihood of developing SUI within a month post-HoLEP (Table 2).

Binary logistic regression analysis identified operative time (OT), MUV, TPWMUS, PAOMU, and total PSA (tPSA) as significant predictors of SUI on univariate scrutiny. Multivariate analysis corroborated OT, TPWMUS, and PAOMU as independent risk determinants, whereas MUV was affirmed as a protective factor against SUI post-HoLEP (Table 3).

Discussion

HoLEP is recognized as a superior surgical modality for the management of BPH, even in patients presenting with enlarged prostates or on anticoagulation therapy (4,13,14). The primary surgical goals are to alleviate LUTS, avert BPH-related complications, and enhance the quality of life. Nevertheless, SUI represents a significant postoperative complaint that impairs the quality of life and impedes surgical recovery (15). Although numerous studies have explored risk factors for SUI, the intricacies of lower urinary tract anatomy have been less frequently addressed. Our investigation has identified not only OT, MUV, and PAOMU but also TPWMUS as an independent risk factor for SUI post-HoLEP, a finding not previously reported in the literature. This study contributes to the understanding of the interplay between lower urinary tract anatomy and SUI, offering insights that could inform strategies to prevent SUI and expedite postoperative convalescence.

Within our patient cohort, MUL was significantly different between those with and without post-HoLEP SUI, echoing to the findings reported by Oka et al. (16). Our analysis suggests that a longer MUL is conducive to a more rapid recovery from SUI post-HoLEP. Urinary continence is predominantly maintained by the smooth muscle of the internal sphincter and the striated muscle of the external sphincter (17,18), and our multivariate analysis indicates that MUV is a significant predictor of SUI post-procedure.

Strasser’s anatomical descriptions suggest the posterior wall of the membranous urethral sphincter forms part of the striated muscle of the external sphincter (19). Our study, however, illustrates that a thicker TPWMUS is an independent risk factor for SUI post-HoLEP. To the best of our knowledge, the thicker posterior wall of the membranous urethral sphincter contributes more to urinary incontinence than the anterior wall. We usually protect the external sphincter by minimizing the use of the cystoscope sheath and using moderate force (20,21). This suggests that due to the leverage principle, the posterior wall, being subject to greater extension than the anterior wall during the procedure, may predispose patients with a thicker TPWMUS to a higher risk of SUI.

The technical complexity of HoLEP is reflected in its steep learning curve (22,23). Even for adept surgeons, the risk of postoperative SUI is a recognized complication (5). The surgeon who performed the surgery in this study was an experienced surgeon who had successfully completed thousands of HoLEPs prior to the start of the study, so the surgical technique had a negligible effect on the results of the study. Postoperative sphincter insufficiency is the main cause of postoperative SUI (24). Our findings emphasize the importance of safeguarding anatomical structures integral to continence. Strategies such as the “omega sign” technique (25), which conserves the mucosal line during prostatic tip enucleation (26), have been shown to mitigate the risk of SUI by minimizing trauma to the external sphincter.

In this study, patients with PAOMU exhibited a higher incidence of SUI, underscoring the significant role of the membranous urethral sphincter and its anatomical relationship with the prostatic apex in urinary continence. The length of the residual urethra post-HoLEP has been proposed as a critical factor for achieving continence, with our findings supporting this hypothesis. There has been precedent for preoperative mpMRI to predict postoperative urinary incontinence, and one article has suggested that the angle of the membranous urethra, as observed by preoperative mpMRI, is associated with urinary incontinence after radical prostatectomy.

HoLEP is more likely to result in external urethral sphincter dysfunction, which can lead to SUI, when preoperative magnetic resonance imaging reveals the presence of any of these risk factors in the patient (MUL <1.4 mm, MUV <1.6 cm³, PAOMU, etc.). Thus an early apical release technique or an alternative procedure, such as TURP, may be used to minimize or avoid the occurrence of postoperative SUI. It has been noted that the use of early apical release, which minimizes the mechanical traction that the external urethral sphincter may be subjected to, has the potential to reduce the incidence of sphincter dysfunction, resulting in a lower rate of postoperative incontinence, but this requires further validation (27-30). Whether the anatomical factors involved in this study are instructive for other surgical approaches such as radical prostatectomy, photoselective vaporization of the prostate, prostatic urethral lift, transurethral microwave therapy, water vapor thermal therapy, thulium laser enucleation of the aquablation and prostate artery embolization requires further trials.

We produced a prediction model (nomogram, see Figure 4) based on the research data and evaluated its performance. The model has good calibration performance on the training set and the test set, and the error on the test set is slightly higher than that on the training set, see Figures 5,6; the decision thresholds are adjusted according to different cost-benefit ratios on the training and test sets to maximize the net benefits, see Figures 7,8. The model’s classification performance on the training set is better, with an AUC value of close to 0.8, which indicates that the model has a high degree of accuracy, and the classification performance on the test set is slightly lower than that of the training set but still within the acceptable range, see Figures 9,10; these indicators show that the model has good prediction ability.

Figure 4 Nomogram. The nomogram shows the score points for different variables including age, tPSA, MUL, MUV, TPWMUS, and PAOMU. By accumulating these score points, a total score can be calculated, and the corresponding likelihood of SUI occurring 1-month post-HoLEP surgery can then be found on the column chart based on the total score. tPSA, total prostate-specific antigen; MUL, membranous urethral length; MUV, membranous urethral volume; TPWMUS, thickness of the posterior wall of membranous urethral sphincter; PAOMU, prostatic apex overlapping the membranous urethra; OT, operative time; SUI, stress urinary incontinence.

Figure 5 Calibration testing. The calibration chart shows the relationship between the predicted probability of the model and the actual probability of occurrence. The points in the graph represent the predicted probability, while the curve represents the actual probability. “Mean absolute error =0.035” indicates an average absolute error of 0.035, indicating a small difference between the predicted and actual values. N=54 indicates that the test set contains 54 samples, and B=1,000 indicates that the bootstrap method was repeated 1,000 times to evaluate the stability of the model. SUI, stress urinary incontinence.

Figure 6 Calibration training. This is the calibration plot for the training set. The mean absolute error is 0.034, indicating that the model also performs well on the training set. n=162 indicates that the training set contains 162 samples. SUI, stress urinary incontinence.

Figure 7 DCA testing. The decision curve analysis shows the normalized net benefit of the model at different high risk thresholds. The curve in the figure represents the cost-benefit ratio between using the model’s forecasts and not using any forecasts (i.e., “None”). Different ratios (e.g., 1:100, 1:4, etc.) represent different cost-benefit trade-offs. DCA, decision curve analysis.

Figure 8 DCA training. This is the decision curve analysis for the training set. DCA, decision curve analysis.

Figure 9 ROC testing. The ROC plot shows the relationship between model specificity (1 − false positive rate) and sensitivity (true positive rate). The point “0.266 (0.860, 0.636)” in the graph indicates the sensitivity and specificity of the model at a specific threshold, where (0.860, 0.636) denotes 95% confidence interval. This interval is extensive, indicating that the sensitivity estimates are very uncertain. This may be due to a small amount of training data or an uneven distribution. The AUC is 0.753, the 95% confidence interval was (0.554–0.951). Which is slightly lower than the AUC of the training set, which may indicate a slight decrease in the model’s performance on new, unseen data. ROC, receiver operating characteristic; AUC, area under curve.

Figure 10 ROC training. This is the ROC plot for the training set. The point “0.215 (0.719, 0.765)” in the graph may indicate the sensitivity and specificity of the model at a particular threshold, where (0.719, 0.765) denotes 95% confidence interval. This interval is also extensive, indicating that the sensitivity estimates are very uncertain. This may be due to a small amount of training data or an uneven distribution. The AUC is 0.774, the 95% confidence interval was (0.684–0.864). which is close to 1, indicating that the model has a good classification performance. ROC, receiver operating characteristic; AUC, area under curve.

Nonetheless, this study’s retrospective nature and the execution of all procedures by a single surgeon limit the generalizability of the results. Future multicenter studies with a larger sample size are warranted to corroborate these findings and enhance the reliability of the data.

Conclusions

OT, membranous urethral sphincter anatomy, and prostatic apex configuration are significant risk factors for SUI post-HoLEP. Membranous urethral volume acts as a protective factor, offering insights for surgical planning and patient counseling.

Acknowledgments

Funding: The study was funded by The National Key Research and Development Program of China (Nos. 2021YFC2009300, and 2021YFC2009304); Guangdong Provincial Clinical Research Center for Urological Diseases (No. 2020B1111170006); and National Natural Science Foundation of China (No. 82473159).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-24-71/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-24-71/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-24-71/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-71/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki (revised in 2013). Patient data were retrospectively reviewed without the need for informed consent. Since the study did not collect or record personally identifiable information, and used only simple contact measuring equipment or observation equipment that did not induce physical changes, it does not require ethical approval.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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