The effect of perioperative pelvic floor muscle exercise on urinary incontinence after radical prostatectomy: a meta-analysis

ABSTRACT Background: Pelvic floor muscle exercise (PFME) is the most common conservative management for urinary incontinence (UI) after radical prostatectomy (RP). We performed this meta-analysis to investigate whether PFME during the entire perioperative period, including before and after RP, can significantly improve the recovery of postoperative UI. Methods: We systematically reviewed randomized controlled trials (RCT) from PubMed, Medline, web of science, Cochrane library, and clinicalitrials.com prior to October 2022. Efficacy data were pooled and analyzed using Review Manager Version 5.3. Pooled analyses of urinary incontinence rates 1, 3, 6, and 12 months postoperatively were conducted, using odds ratio (OR) and 95% confidence intervals (CIs). Results: We included a total of 15 RCT studies involving 2178 patients received RP. Postoperative UI could be improved after 1 month, 3 months and 6 months, and the OR were 0.26 (95%CI:0.15-0.46) 0.30 (95%CI: 0.11-0.80) 0.20 (95%CI: 0.07- 0.56) in postoperative PFME group compared to no PFME group. However, there was no significant difference between the two groups in 12 months after surgery, and the OR was 0.85(95%CI: 0.48,1.51). There were similar results in perioperative PFME group compared to no PFME group with the OR of 0.35 (95%CI: 0.12, 0.98) and 0.40 (95%CI: 0.21, 0.75) in 1 and 3 months after surgery. Our results indicated no significant difference between perioperative PFME group and postoperative PFME group. The OR was 0.58 (95%CI: 0.20-1.71) 0.58 (95%CI:0.20-0.71) and 0.66 (95%CI: 0.32-1.38) in 1, 3 and 6 months after surgery. Conclusion: Application of PFME after RP significantly reduced the incidence of early postoperative UI, and additional preoperative PFME had no significant improvement on the recovery of UI.


INTRODUCTION
Prostate cancer is the second most common cancer and the fifth leading cause of cancer death among men, with about 1.4 million new cases and about 375,000 deaths worldwide in 2020 (1).More and more male patients have the opportunity to undergo radical prostatectomy (RP) when prostate cancer is still early and localized with increasing health awareness (2,3).However, RP can cause some troublesome complications affecting patients' quality of life, including persistent and troubling urinary incontinence (UI).It was reported that more than 80% of patients suffered from UI one month after RP, and 3-12% still existed UI one year after RP (4).UI after RP is mainly caused by the lack of strength of urethral sphincter (5,6).Pelvic floor muscle exercise (PFME) (7,8) is the most common conservative treatment for postoperative UI via continuously contracting and relaxing the pelvic floor muscles to increase pelvic floor muscle tone and improve urinary tract resistance.Previous studies have demonstrated the safety and validity of PFME on UI after RP (6), however, there were a few controversies of when to conduct PFME in recent studies including several reviews (9,10).We thereby performed this meta-analysis to investigate whether PFME during the entire perioperative period, including before and after RP, can significantly improve the recovery of postoperative UI.

Database searching and literature screening.
A comprehensive literature search was conducted on PubMed, Medline, Web of Science, Cochrane Library and ClinicalTrials.gov, to obtain all relevant English articles published before Oct.2022.The search strategy was: (radical prostatectomy) AND (urinary incontinence) AND (pelvic floor muscle exercise) according to the PICOS principle.Three reviewers screened all the titles and abstracts independently.The language was restricted to English, and articles studying the impact of PFME on recovery of UI after RP were included for further screening.We con-ducted this meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).

Inclusion criteria and exclusion criteria
Articles that met the following criteria were included: (1) Randomized controlled trials (RCTs).( 2

Data extraction
Data extraction was performed independently by three researchers.We extracted the study's primary characteristics, including the first author, sample size, year of publication, PFME regimens, follow-up time and incidence of UI.Any differences have been re-solved by discussion.

Quality evaluation
Quality of included studies was evaluated by the Cochrane Collaboration's tool for assessing risk of bias.The tool consists of seven parts: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias.Each part can be graded as low risk of bias, unclear risk of bias, and high risk of bias (Supplementary Figure -2).
Two reviewers carried out this assessment procedure independently and reached a consensus through discussion if disagreements appeared.

Statistical Analysis
Outcome data were pooled and analyzed with the Review Manager (RevMan) Version 5.3.and presented as odds ratio (OR) with 95% confidence interval (CI) at different follow-up time points.Heterogeneity among studies was evaluated by the I2 test, with I2 > 50% considered to be of significant heterogeneity.In case of significant het-erogeneity, random effects model was selected to analyze the outcome data and sensitivity analysis was performed to detect the source of heterogeneity.Intergroup difference was considered to be statistically significant when P < 0.05.

Quality of included studies
Studies were assessed as moderate-to-high quality according to the Cochrane Collaboration's tool for assessing risk of bias (Figure -2).Eight studies clarified the method of randomization, and it was reasonable and low risk.Six studies only mentioned randomization without explaining the method, and only one article was high-risk (13).In addition, nearly half of the studies hid the allocation strategy.Studies had a high risk of performance bias caused by the impossibility of par-   ticipants and personnel blinding.Therefore, we did not exclude studies just because of the high risk of performance bias.In most trials, the data analyst did not know the grouping and treatment of the trial.The follow-up information was detailed described in most studies.There was also no significant publication bias and other bias in these studies.

DISCUSSION
Persistent and disturbing UI is a common complication after RP, with an incidence of 30-40% in early follow-up after surgery.Detrusor overactivity and intrinsic sphincter insufficiency due to sphincteric injury are the most important causes of persistent incontinence after radical prostatectomy.Some reports mention that detrusor overactivity is a significant cause of post-prostatectomy incontinence, others strongly argue that even if other factors play a role, the main cause of UI after RP is intrinsic sphincter deficiency (25,26).The absence of both functions can be corrected by PFME, which is not only convenient and practical, but also has no other side effects.PFME can increase the activation of tension muscles, then transfer to the functional tasks of other muscles.It not only enhances the contractile force of the transverse urethral sphincter, but also compensates for the lack of urethral smooth muscle function, so as to improve the urethral pressure.In addition, PFME can provide more support and restraint for the bladder and urethra, thus reducing the over-activity of the detrusor muscle (5,27).
A number of studies have proved that PFME has a significant improvement effect on postoperative UI, and increasing the intensity of PFME can accelerate the recovery of urinary incontinence (28), but there has been controversy over the starting time of PFME.Our results showed that both perioperative and postoperative PFME helped to reduce the occurrence of UI in the early postoperative period, while there was no significant improvement in 12 months, consistent with Rangganata et al. (29).Compared with postoperative PFME, perioperative PFME did not bring significant benefits on the improvement of patients' early postoperative UI, which is consistent with the results of Wang et al. and Gislano et al. (6,12,28).However, some studies have shown that patients who start to learn and use PFME before surgery can reduce the occurrence of postoperative UI, and the data is statistically significant (29,30).We reviewed relevant studies and summarized the following two possible reasons: First, patients can fully perceive the contraction of the PFME without pain, to make the PFME more effective after surgery, and thus accelerate the recovery of UI.Secondly, preoperative PFME makes the overall pelvic floor muscle fibers more robust, which makes the damage and influence of RP on PFME relatively small, and thus reduces the occurrence of postoperative UI (7,9).However, preoperative PFME also has some disadvantages, such as increasing the consumption of patients' time and energy.It is also easy to cause patients' anxiety before surgery (31).Whether PFME is necessary before RP needs to be further analyzed by sufficient studies.
There are some limitations in this metaanalysis.First, there is a certain heterogeneity among studies mainly caused by the diversity of PFME schemes in the studies.Other factors included the differences of definition of UI, the intensity and frequency of interventions, and surgical procedures (32,33).In addition, the included studies could not blind the experimenters and the interveners in this study with PICO, which may affect the results.

CONCLUSIONS
Application of PFME after RP can significantly reduce the incidence of early postoperative UI, and additional preoperative PFME had no significant improvement on the recovery of UI.Urologists should instruct the patient to perform PFME after removing the catheter, while preoperative PFME is not necessary.

Figure 1 -
Figure 1 -Flow diagram of literature searches according to the preferred reporting items for systematic reviews and metaanalyses statement.

Figure 2 -
Figure 2 -Risk of bias of included studies.

Figure 3 -
Figure 3 -Meta-analysis of objective cure of UI between PFME and No PFME.

Figure 4 -
Figure 4 -Meta-analysis of objective cure of UI between Perioperative PFME and No PFME.

Figure 5 -
Figure 5 -Meta-analysis of objective cure of UI between Perioperative PFME and Postoperative PFME.