To sling or not to sling? Impact of intraoperative sling procedures during radical prostatectomy on postoperative continence outcomes: A systematic review and meta‐analysis

Abstract Purpose This systematic review and meta‐analysis investigates the efficacy of intraoperative sling procedures in reducing postprostatectomy urinary incontinence compared to having no slings. Methods A comprehensive search of PubMed, Medline, Embase, and the Cochrane library from inception to November 2020 was performed. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized studies and Newcastle‐Ottawa Scale for nonrandomized studies. The GRADE approach was used for critical appraisal of evidences and meta‐analyses were conducted using random‐effects models. Results Ten studies were included (n = 1,447). Quality of evidence ranged from moderate to very low. Sling procedure was generally favorable for short‐term continence outcomes, although discrepancies exist due to variability in continence definition. Sling procedure resulted in reduced urinary pad weight at 1 month postoperatively (MD: 21.55; 95%CI: 12.58 to 30.52). Patient‐reported questionnaires were also favorable for the sling group for up to 3 months (IPSS; (MD: 1.44; 95%CI: 0.14 to 2.74), ICIQ‐SF; (MD: 2.25; 95%CI: 1.26 to 3.24), EPIC‐U; (MD: 5.30; 95%CI: 1.12 to 9.39)) postoperatively. Sling procedure improved the number of continent patients at 1 month with continence definition of zero pad use/day (RR:1.41; 95%CI: 1.10 to 1.83) but not with the definition of ≤ 1pad/day. Similarly, it reduced the time to continence with the ≤ 1 pad/day definition (MD: 0.5; 95%CI: 0.1 to 0.9) but not with the zero pad/day definition. Conclusion The current literature suggests that intraoperative sling procedures during radical prostatectomy may promote early return of continence compared to having no sling, however, there are no long‐term differences.


| INTRODUC TI ON
Prostate cancer is the second most common malignancy in men worldwide, with 1.3 million new cases in 2018. 1 Radical prostatectomy is an effective and commonly performed treatment option for localized prostate cancer. 2 However, urinary incontinence remains a major adverse event following radical prostatectomy, with 12 months postoperative urinary incontinence rate ranging from 4% to 31%. 3 Urinary incontinence can have a severe impact on the patient's quality of life, and thus, remains a deterrent for many patients when deciding treatment for their prostate cancer. 3 Multiple etiologies have been proposed for the development of postoperative incontinence with the major factor attributed to intraoperative damage of the urethral sphincter with accompanying intrinsic sphincter deficiency. 4 Other possible causes include detrusor over and under-activity, bladder outlet obstruction due to anastomotic strictures and damage to pelvic nerves that potentially supply the sphincter mechanism. As such, several intraoperative techniques aiming to reduce postoperative urinary incontinence have been described, including surgical techniques to preserve anatomical structures (ie, bladder neck, neurovascular bundle, or puboprostatic ligaments) and different surgical approaches including anterior and posterior reconstruction and the Retzius-sparing technique. 5,6 However, the role of these intraoperative techniques in reducing incontinence remains unclear; with many of these techniques not externally validated in a multicenter setting. [7][8][9] Recent studies suggest that the use of intraoperative suburethral sling techniques during prostatectomy may reduce the incidence of postoperative urinary incontinence. 10 Sling suspension technique involves the placement of a sling to support the proximal urethra and bladder neck to provide compressive force on the urethra, increase the functional length of the urethra and maintain adequate urethral closure. 5 Sling techniques are commonly used in the setting of postoperative urinary incontinence when noninvasive therapies such as pelvic floor muscle training and pharmacologic treatments fail. 11 Performing a sling procedure intra-operatively at the time of prostatectomy may prevent the development of urinary complications, improving postoperative quality of life and reducing overall cost by minimizing the likelihood of patients having to undergo secondary surgery for incontinence following radical prostatectomy.
Different surgical techniques and sling materials have been explored with varying results. Therefore, the purpose of this study is to conduct a systematic review and meta-analysis to evaluate the effectiveness of intraoperative slings compared with no sling procedure in reducing postoperative urinary incontinence and complication rates in patients undergoing radical prostatectomy. Trials (CENTRAL) via the Cochrane Library, using key words related to "prostate cancer," "prostatectomy," "sling," and "urinary incontinence" (Table S1). No language restrictions were applied. In addition, reference lists of all included studies were screened.

| MATERIAL S AND ME THODS
One reviewer inspected the titles and abstracts of all identified studies to generate a list of potentially eligible studies (EL). Full-text articles were reviewed by two review authors for eligibility (EL and DS). Consensus between the two reviewers was used to resolve any disagreement.

| Inclusion and exclusion criteria
The studies included in this review reported data on localized prostate cancer patients who underwent radical prostatectomy at any age. Study types included randomized controlled trials and nonrandomized comparative studies.
Exclusion criteria includes animal studies, conference abstractions or poster publications, and descriptive commentaries.

| Outcome measures
The main outcomes of interest were urinary incontinence and other adverse events or complications. Length of hospital stay, length of operation, quality of life, and cost were also investigated.

| Data extraction
Two review authors used a pre-piloted data extraction sheet to extract data from the included studies (EL and DS). Consensus between the two reviewers were used to resolve any disagreement. An attempt was made to contact authors from studies where data were unclear or not available in the published manuscript.
For each included study the following data were extracted: sample characteristics (country, study design, surgical procedure, sling position, sling material, age, body mass index, prostate specific antigen (PSA)), name of sling procedure used, and all outcome measures from all time points.

| Risk of bias assessment and strength of the evidence
Cochrane Collaboration's tool was used to assess the methodological quality of randomized controlled trials. 12 Each study was assessed as having high, low, or unclear risk of bias by two reviewers (EL and DS).
Methodological quality of comparative studies was assessed via the Newcastle-Ottawa Scale (NOS), which was endorsed by the Cochrane handbook for quality appraisal of observational studies. 14,15 Each study was given a score between zero and nine, by considering three factors that consist of nine items in total: (1) Selection of study groups, (2) Comparability and (3) Outcome of interest. 14 Our review considered a study with a score of ≥ 7 as having high quality and low risk of bias, as there are no established standardized criteria for the interpretation of the NOS scores currently. Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess strength of evidence from high to very-low-quality for each outcomes. 16

| Statistical analysis
For dichotomous outcomes, we extracted the number of patients in each group who experienced the outcome of interest and the number of patients assessed at endpoint in each treatment arm at the end of the prespecified follow-up, in order to estimate a relative risk and its 95% confidence interval. For continuous outcomes, we extracted the final value and standard deviation of the outcome of interest and the number of patients assessed at the endpoint in each treatment arm at the end of follow-up. Where appropriate, we calculated the mean difference and 95% confidence interval.
Outcome measures from individual trials were combined through a meta-analysis where possible using a random-effects model, via the Comprehensive Meta-Analysis software. 17 When a meta-analysis was not possible, results were described qualitatively.
Included studies were grouped by outcome measures (eg, continence defined as zero pad/day), followed by time frame (1, 3, 6, and 12 months) to provide a homogenous subset for meta-analysis. Time points (1, 3, 6, and 12 months) were selected based on the available results. Studies included in the meta-analysis were ordered chronologically.

| Literature search
The search identified 179 citations after the removal of duplicates.
Following the elimination of irrelevant references, 31 full-text articles were screened for eligibility. About 21 articles were excluded due to

TA B L E 1 Characteristics of the included studies
Author
The mean age reported in the studies was 62.06. All studies found were in English. The characteristics of included studies including type of surgical approach are presented in Table 1.

| Risk of bias assessment
The risk of bias assessments of the included studies are presented in Tables 2 and 3.

| Cochrane collaboration's tool for randomized controlled trials
Three studies had at least one domain with high risk of bias ( Table 2).
The most common methodological flaw was found in the "blinding of participants and personnel" and "other source of bias," which included selection bias and recall bias. Least methodological flaws were found in the domain of "selective reporting."

| Newcastle-Ottawa scale for comparative studies
One study was assessed to have low risk of bias and four studies had high risk of bias ( Our meta-analysis demonstrated a very-low to moderate-quality evidence that with continence defined as using zero pad/day, number of continent patients is significantly increased in the sling group

| Length of hospital stay, length of operation, quality of life and cost
Cestari et al. 19 reported that sling procedure does not reduce hospital length of stay (MD: 0.0; P-value not reported; 95% CI not reported) (n = 60). Sling procedure, however, resulted in increase in the length of operation (MD: −6.13, 95%CI: −9.18 to −3.07) ( Figure 6).
Our search did not find any study investigating differences in quality-of-life outcomes and cost.

| D ISCUSS I ON
Our systematic review demonstrates that there is a low-moderate certainty evidence that intraoperative sling procedures are generally TA B L E 3 Risk of bias assessment of comparative study via Newcastle-Ottawa Scale Note: The score ranges from 0 to 9 points. Study with a score of ≥ 7 was considered as having high quality and low risk of bias. reduces the time taken to achieve continence with ≤ 1 pad/day definition but not with zero pad/day definition.
Our meta-analysis also demonstrated that intraoperative sling may reduce the incidence of postoperative complications such as urethral stricture and urinary retention, however, no explanation as to why this is the case was provided in the included studies. Sling procedure increased the operative time but did not affect the length of hospital stay.

| Comparison with other studies and future directions
To our knowledge, this is the first systematic review and metaanalysis that evaluates the effectiveness of intraoperative sling procedures compared to having no sling procedures on postprostatectomy continence outcomes. Our review demonstrates the importance of standardizing the definition of continence for utilization in future studies. Although defining continence via pad number is a common clinical practice, it is not a reliable measure of urine leakage as it is largely affected by pad size and type as well as the variability of individual patient's perception of when to change the pads. 27 Thus, pad weight measurement via 24-hour pad test is a more objective assessment of urinary incontinence for use in future studies. 27,28 Additionally, questionnaires are objective assessment tools that also allow the evaluation of patient's postoperative quality of life, and thus, provide a better assessment of sling effectiveness. 27 Furthermore, our review demonstrates that current studies in the field of intraoperative sling technique have very-low-quality to moderate-quality, identifying the need for future studies with high-quality evidence.
Our review also suggests that future studies assessing the effectiveness of intraoperative sling must consider the type of sling material used. The sling materials used in all studies included in our review are biological absorbable graft materials, and as they are known to degrade very quickly, this may be one reason for poor outcome. Our review demonstrates that there are no significant difference in continent patients between the sling and no-sling group beyond 6 months postoperatively. This may be influenced by the fact that biological sling materials are absorbed after 6 months.

| CON CLUS ION
Overall, our study demonstrates that intraoperative sling procedures do not decrease long-term urinary incontinence rate, however, may have potential to promote early return of continence. Currently, our evidence is limited by the lack of high-quality studies and variability in definitions, and as thus our study details how future clinical research in this field can be improved in order to verify the effect of intraoperative slings more effectively.