Predictors of urinary outcomes following robotic‐assisted laparoscopic prostatectomy

Abstract Introduction Incontinence and urgency are common after prostatectomy. The University of Virginia prostatectomy functional outcomes program (PFOP) was developed to comprehensively assess and optimise continence outcomes following robotic‐assisted laparoscopic prostatectomy (RALP). Patients are prospectively evaluated by a Female Pelvic Medicine and Reconstructive Surgery specialist. This study assessed for predictors of 3‐ and 6‐month stress urinary incontinence (SUI) and urgency symptom outcomes following RALP. Methods We performed a post hoc review of patients from our PFOP receiving a minimum of 6‐month follow‐up. Urinary symptoms are prospectively assessed using the validated International Consultation on Incontinence Questionnaire‐Male Lower Urinary Tract Symptoms (ICIQ‐MLUTS) questionnaire and daily pad use (pads per day [PPD]). Primary study outcomes included ICIQ‐MLUTS SUI and urgency domain scores and PPD. Multivariable linear regression was performed to identify variables associated with outcomes at 3 and 6 months postoperatively. Variables included patient, oncologic and surgical factors. Each variable was run in a separate model with pelvic floor muscle therapy and surgeon to reduce confounding and prevent overfitting. Results Forty men were included. In assessment of ICIQ‐MLUTS SUI domain score, at 3 months, body mass index (BMI) was associated with worse scores, and at 6 months, BMI, hypertension and estimated blood loss (EBL) were associated with worse scores, whereas bilateral nerve‐sparing technique was associated with better scores. For ICIQ‐MLUTS Urgency domain score, at 3 months, preoperative use of benign prostatic hyperplasia (BPH) medication was associated with better scores. No covariates predicted 6‐month ICIQ‐MLUTS Urgency domain scores. For PPD use, at both 3 and 6 months, BMI was a positive predictor, while preoperative use of BPH medication was a negative predictor. Conclusion Increased BMI, EBL and hypertension are associated with worsened SUI outcomes following RALP, whereas bilateral nerve‐sparing technique and preoperative BPH medication are associated with improved SUI outcomes. These data may inform patient counselling and help identify patients who may benefit from closer surveillance and earlier anti‐incontinence intervention.

inform patient counselling and help identify patients who may benefit from closer surveillance and earlier anti-incontinence intervention.

K E Y W O R D S
BMI, nerve sparing, RALP, risk factors, stress incontinence, urge incontinence

| INTRODUCTION
Incontinence and urgency are common adverse outcomes after prostatectomy and can contribute to patient distress. 1,2While many patients have improvement or cure spontaneously with conservative management, many have persistent bothersome symptoms requiring surgical intervention. 3,4The American Urologic Association (AUA)/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction Guideline on Incontinence after Prostate Treatment recommends immediate post-prostatectomy pelvic floor muscle training (PFMT) and recommends considering surgery as early as 6 months for persistent bothersome symptoms, although many patients are not treated until much later, prolonging distress and reduced quality of life (QOL). 5,6The ability to identify baseline and surgical characteristics as predictors of incontinence outcomes will help identify patients who may benefit from closer post-operative surveillance and timely intervention.
The University of Virginia prostatectomy functional outcomes program (PFOP) was developed to comprehensively assess and optimise continence outcomes following robotic-assisted laparoscopic prostatectomy (RALP).Patients are evaluated by a Female Pelvic Medicine and Reconstructive Surgery (FPMRS) specialist at baseline, 3, 6 and 12 months following surgery.With this cohort of patients, this study assessed for predictors of 6-month stress urinary incontinence (SUI) and urgency symptom outcomes following RALP using linear regression.Inclusion criterion was a minimum follow-up of 6 months.

| RESULTS
A total of 40 patients were included in the analysis, undergoing RALP between 2018 and 2021.No patients were excluded for missing data.
Patients underwent robotic radical prostatectomy by three different experienced surgeons using techniques including anterior approach, anterior approach with Hood technique reconstruction and Retziussparing approach.Average catheter time was 7-10 days for all patients.Table 1 provides a detailed summary of patient demographics and surgical characteristics.
Questionnaire outcomes are detailed in Table 2.In summary, a significant deterioration was seen in SUI and urgency domain scores from baseline to 3 months postoperatively with a significant increase in PPD used.From 3 to 6 months, there was improvement in all outcomes; however, scores remained significantly higher at 6 months compared with baseline.

| Multivariable analysis
Table 3 shows the multivariable analysis outcomes at 3 months, and Table 4 shows the multivariable analysis outcomes at 6 months.

| Urinary urgency
Pre-operative BPH medication use was found to be a significant factor in improved urgency domain score at 3 months (β = À0.96,p = 0.0096).No risk factors were found to significantly predict postoperative urgency outcomes at 6 months.

| Pad use
BMI was significantly associated with greater PPD use postoperatively at 3 months (β = 0.21, p = 0.0028), while pre-operative BPH medication use was found to be a significant factor in improved PPD use at 3 months (β = À1.9, p = 0.015).BMI was significantly associated with greater PPD use postoperatively at 6 months (β = 0.091, p = 0.022), while pre-operative BPH medication use was found to be a significant factor in improved PPD use at 6 months (β = À0.96,p = 0.027).

| DISCUSSION
Incontinence after RALP is a common issue with significant patient bother and negative impact on QOL.persistent bothersome SUI, intervention is often delayed, prolonging decreased QOL. 5,6In this post hoc analysis of prospectively collected incontinence outcome data in patients undergoing RALP, we aimed to identify risk factors for worse post-prostatectomy incontinence at 6 months to facilitate early identification of patients who may benefit from early anti-incontinence intervention.
We identified the patient factor of higher BMI as a predictor of worse SUI at 3 and 6 months postoperatively.Additionally, HTN was identified as predictors of worse SUI at 6 months postoperatively.
While others have also reported BMI predictive of worsened incontinence outcomes following prostatectomy, 6,7 HTN has previously been found as not predictive. 8It is likely that BMI and HTN are colinear and that multivariable modelling in larger population may identify one instead of the other as the true predictor.Overall, prior studies of patient-specific predictors of post-prostatectomy incontinence are mixed, with some identifying age, prostate size and smoking status all predictive of worse outcomes, 7,9,10 while others find these not predictive as was the case in our study. 8terestingly, we also found that preoperative BPH medication use was associated with fewer PPD used at 3 and 6 months postoperatively and decreased urgency at 3 months postoperatively.We used this variable as a surrogate for clinically significant preoperative BPH.This finding is surprising as prior study has also identified preoperative LUTS and predictor of worse post-prostatectomy incontinence outcomes. 7There is little data however on preoperative BPH and BPH medication use in relation to post-prostatectomy incontinence. 10We did not collect information regarding specific BPH medications used (i.e.alpha-blockers versus 5-alpha reductase inhibitors); however, one possible explanation for these findings is that the androgen ablative effect of 5-alpha reductase inhibitors could theoretically favourably affect surgery resulting in better incontinence outcomes.
T A B L E 2 Patient-reported urinary outcomes.Our study also identified surgical factors of bilateral nerve sparing and lower EBL as protective against post-operative SUI at 6 months.
These are not surprising.Neural factors have a known essential role in post-prostatectomy incontinence as denervation of the sphincter disrupts continence, 11 and the AUA Guideline on Incontinence after Prostate Treatment recognise bilateral nerve-sparing approach to prostatectomy as only protective surgical manoeuvre linked with improved post-operative continence. 6Additionally, others have also found higher EBL associated with worse SUI outcomes. 12EBL could be a marker of increased surgical difficulty, lead to decreased visibility and more injury to neurovascular bundles and/or sphincter. 13though not stated in the AUA guidelines for incontinence after Prostate Treatment, Retzius-sparing is a surgical technique that has been shown in the literature to reduce post-RALP SUI. 14 Umari et al.
demonstrated an immediate improvement of incontinence at time of catheter removal; however, there was no difference in ICIQ MLUTS stress incontinence prevalence at 1 month between the Retziussparing RALP and non-sparing RALP groups. 15Liao et al. also demonstrated improved immediate continence, but at 6 months, there was no difference between Retzius-sparing RALP and RALP groups. 16Our analysis demonstrated that there was no significant improvement in SUI outcomes with Retzius-sparing RALP at 6-month follow-up.
Retzius-sparing approach was not predictive of SUI outcomes at 6 months in this study, which is consistent with prior study.Although this approach has been associated with earlier return to continence on the order of weeks to months, 14,15 no differences have been found at 6 months compared with standard non-Retzius-sparing approaches. 16tably, there were no predictors in our study that were associated with urinary urgency.Overall, urgency is understudied in post-RALP patients although it is known to be common.It has been shown that urgency occurs in 19%-48% patients post-prostatectomy, 17,18 These symptoms can be burdensome, and intervention could benefit QOL.Further study is necessary to investigate this common adverse outcome after prostatectomy.
Our findings can be utilised to guide post-prostatectomy followup protocols.Patients identified as higher risk for worsened SUI at 6 months, such as obese hypertensive patients who underwent nonnerve sparing RALP with high EBL, may be followed more closely postoperatively by an FPMRS or GURS specialist.This would allow for comprehensive and improved evaluation and possibly earlier surgical intervention, if indicated.Historically, surgical intervention for SUI was delayed until 12 months post-RALP; however, recent literature shows that surgical intervention can be initiated at 6 months for persistent bothersome symptoms; as only a small number of patients will improve their continence after 6 months, 6,19 Nelson et al. demonstrated that the median time for surgical intervention for post-RALP SUI is 23.5 months. 5e study is limited by its retrospective nature and a smaller sample size.The sample size is a function of the programme feasibility.
Given the significant time requirements required of a single FPMRS specialist needed to conduct in-person visits numerous times throughout the post-operative year, it was not possible to enrol all patients undergoing RALP.That said, we are aware of no other study assessing outcomes in this fashion.Indeed, oncologic surgeons had no access to study data until the analysis phase.In addition, in an effort to account for smaller sample size, our multivariable modelling was limited to considering candidate predictors in isolation while controlling for surgeon and PFMT to avoid over-fitting.The present cohort is also heterogeneous and, based on the programme participation methodology, subject to bias.That said, we believe that this quality is more consistent with the outcomes seen in community practice and, combined with the strength of validated and longitudinal data, allows urologists further insight into functional outcomes over time that may be used to counsel patients.Additional assessment is ongoing to evaluate other clinical questions including potential functional outcomes differences between in-person PFMT and standard unsupervised pelvic floor exercises, as well as urgency and SUI outcomes over time.
performed a retrospective review of patients undergoing RALP for prostate cancer and who were participating in the University of Virginia PFOP.The University of Virginia PFOP was developed as a clinical initiative to comprehensively assess and optimise functional outcomes following RALP.Accordingly, this programme was created and supervised by a FPMRS specialist (DER).Patients undergoing RALP by any of three surgeons were contacted by the programme team and offered participation in the programme to include in person visits with the FPMRS specialist to allow for comprehensive symptom assessment and in-person pelvic floor muscle training, dietary counselling, and behavioural training.Those patients declining participation in this fashion were offered virtual follow-up focused on functional outcomes.In this case, pelvic floor and behavioural education was provided by the patients treating RALP surgeon.Importantly, this programme is unique in that all outcomes were assessed independently by the FPMRS specialist in an effort to optimise accuracy of data and focus on optimising outcomes.Functional outcomes assessment and surveillance is longitudinally performed in patients undergoing RALP using robust questionnaires, with lower urinary tract symptoms prospectively assessed using the validated International Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) questionnaire and daily pad use at each follow-up visit.Questionnaire assessment is performed at baseline and at 3-week and 3-, 6-and 12-month timepoints following RALP.The present study represents a retrospective analysis of data collected as part of this clinical initiative.All patients with 6-month follow-up were eligible for analysis.Based on the programme characteristics, the study cohort represents a sample of patients from the overall population of patients undergoing RALP at our institution (40 out of 196 patients undergoing RALP during the analysis period).Multivariate analysis was performed to assess for predictors of both SUI and urgency symptoms within the first 6 months following RALP.The primary study outcomes included ICIQ-MLUTS SUI and urgency domain scores and pads per day (PPD).As part of this programme, patients are also offered directed inperson PFMT by an FPMRS-trained specialist (DER).Patients declining in-person PFMT undergo a standard post-operative rehabilitation pathway, with pelvic floor exercises directed by the primary oncologic surgeon.Assessment of outcomes related to in-person versus unsupervised PFMT is the focus of separate research study.
Statistical analysis was performed using SAS version 9.4 (SAS InstituteInc., Cary, NC, USA), and P-values less than 0.05 were considered statistically significant.Data are presented as mean (standard deviation) or n(%), as appropriate.The present analysis focused on SUI (ICIQ-MLUTS SUI domain score and daily pad use) and urgency (ICIQ-MLUTS urgency domain score) outcomes following RALP.Accordingly, multivariable linear regression was performed to identify variables associated with SUI and urgency outcomes at 6 months following RALP.The variables of interest included body mass index (BMI), hypertension (HTN), pre-operative BPH medication use (alpha-blockers and/or 5-alpha reductase inhibitors), smoking status, age, pre-operative prostate specific antigen (PSA), adjuvant external beam radiation therapy (XRT), prostate size, estimated blood loss (EBL), Retzius-sparing technique, bilateral nerve sparing (BNS), unilateral nerve sparing (UNS) and lymph node dissection (LND).The model was adjusted for the presence of pelvic floor muscle therapy and surgeon.Each variable of interest was run in a separate model with pelvic floor muscle therapy and surgeon to prevent overfitting.

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CONCLUSIONIncreased BMI, EBL and the presence of HTN are associated with worsened SUI outcomes following RALP, whereas bilateral nerve sparing technique and preoperative BPH medication are associated with improved SUI outcomes.These data may inform patient counselling and guide post-operative follow-up, as patients with elevated BMI, HTN or higher intraoperative EBL may benefit from closer surveillance and earlier anti-incontinence intervention.
1,2Despite national guidelines recommending intervention as early as 6 months postoperatively forT A B L E 1 Patient characteristics.
a Significantly differed from baseline to 3 months.bSignificantlydiffered from baseline to 6 months.T A B L E 3Note: Multivariable linear regression for urinary symptom outcomes (ICIQ-MLUTS SUI domain score, ICIQ-MLUTS Urgency domain score and pads per day).Coefficients for each risk factor are controlled for surgeon and pelvic floor muscle therapy.P-values <0.05 are bolded.Abbreviations: bilat, bilateral; BMI, body mass index; BPH, benign prostatic hyperplasia; EBL, estimated blood loss; lymph n., lymph node; med, medication; PSA, prostate specific antigen; unilat, unilateral; XRT, adjuvant external beam radiation therapy.
T A B L E 4 Predictors for urinary symptom outcomes following RALP (6 months).Multivariable linear regression for urinary symptom outcomes (ICIQ-MLUTS SUI domain score, ICIQ-MLUTS Urgency domain score and pads per day).Coefficients for each risk factor are controlled for surgeon and pelvic floor muscle therapy.P-values <0.05 are bolded.