Efficacy of surgical treatment for post-prostatectomy urinary incontinence: a systematic review and network meta-analysis

Objectives:

Post-prostatectomy urinary incontinence (PPUI) is a major complication that reduces the quality of life in patients undergoing prostatectomy for benign prostatic hyperplasia and prostate cancer. However, there are currently limited guidelines on which surgical techniques are preferred after conservative treatment for PPUI. In this study, a systematic review and network meta-analysis (NMA) that can help determine the priority for the selection of surgical methods were performed.

Materials and methods:

We retrieved data from electronic literature searches of PubMed and the Cochrane Library through August 2021. We searched for randomized controlled trials studies on the surgical treatment of PPUI after surgery for benign prostatic hyperplasia or prostate cancer and included the terms artificial urethral sphincter (AUS), adjustable sling, nonadjustable sling, and injection of the bulking agent.

The NMA pooled the odds ratios and 95% credible intervals (CrIs) using the number of patients achieving urinary continence, weight of pads used per day, number of pads used per day, and the International Consultation on Incontinence Questionnaire score. The therapeutic effect of each intervention on PPUI was compared and ranked using the surface under the cumulative ranking curve.

Results:

A final 11 studies, including 1116 participants, were included in our NMA. The pooled overall odds ratios of patients achieving urinary continence compared with no treatment was 3.31 (95% CrI: 0.749, 15.710) in AUS, 2.97 (95% CrI: 0.412, 16.000) in adjustable sling, 2.33 (95% CrI: 0.559, 8.290) in nonadjustable sling, and 0.26 (95% CrI: 0.025, 2.500) in injection of bulking agent. In addition, this study shows the surface under the cumulative ranking curve values of ranking probabilities for each treatment performance, which indicated that AUS ranked first in terms of continence rate, International Consultation on Incontinence Questionnaire, pad weight, and pad use count.

Conclusion:

The results of this study suggested that only AUS had a statistically significant effect compared to the nontreatment group and the highest PPUI treatment effect ranking among other surgical treatments.

Highlights

• Post-prostatectomy urinary incontinence (PPUI) is a major complication that reduces the quality of life after prostatectomy.

• There are currently limited guidelines on post-prostatectomy urinary incontinence.

• This study can help determine the priority for the selection of surgical methods.

• Artificial urethral sphincter demonstrated a statistically significant effect compared to nontreatment group.

Introduction

Benign prostatic hyperplasia (BPH) is a common health problem in which 75% of men over the age of 50 years suffer from related symptoms. It mainly affects older men, and 20–30% of men over the age of 80 years require surgical treatment1–3. One-sixth of all men will be diagnosed with prostate cancer (PCa) in their lifetime and it is the leading cause of cancer-related deaths in men. PCa is a common cancer in Europe and the United States, and its incidence tends to increase sharply after the age of 55 years, showing a high correlation with age4–7.

Prostate surgery is a standard treatment for BPH and PCa. The gold-standard intervention for the treatment of obstructive symptoms due to BPH is transurethral resection of the prostate (TURP)8. TURP generally has a low complication rate, but urinary incontinence (UI) has been reported to occur in 1.8–5.0% of patients9–12. Holmium-laser enucleation of the prostate (HoLEP) has recently been widely performed based on its proficiency in enucleating a large prostate (exceeding 100 g) among the elderly and its similar effect to TURP13,14. In a study by Das et al.13, the prevalence of transient post-prostatectomy urinary incontinence (PPUI) after HoLEP was 8.8%, and that of long-term PPUI was 1.5%. The standard treatment for localized PCa is radical prostatectomy (RP), which has demonstrated an oncological benefit for intermediate and high-risk groups and has a high 5-year survival rate of 95%. However, despite the advances in surgical techniques and the emergence of minimally invasive procedures including robotic-assisted laparoscopic prostatectomy (RALP) and laparoscopic RP, the risk of complications such as UI still exists5,15,16. Although there are studies stating that RALP showed better postoperative functional outcomes compared to other modalities, other studies suggested that RALP was not related to improvements in the prevalence of PPUI17,18.

PPUI caused by surgical injury to the urinary sphincter, pelvic floor muscle damage, or detrusor overactivity lowers the patient’s quality of life and causes economic burden4,19,20. Risk factors for PPUI include old age, obesity, comorbidities, impaired bladder function, and prostate volume19,21. The prevalence of PPUI varies from 6.3 to 52%, depending on the nature of the study22. This variability in the prevalence is due to the definition of PPUI used in the study. In the study by Tienza et al.23, when PPUI was strictly defined by patients symptom, the prevalence was 23%; whereas when PPUI was defined as using more than one pad per day, the prevalence was 11.9%.

Treatment for PPUI can be either noninvasive or invasive24. Noninvasive approaches include lifestyle management, pelvic floor muscle exercise, and medical treatment. The invasive approaches include surgical treatment such as injection of urethral bulking agents, artificial urethral sphincter (AUS) insertion, and adjustable or nonadjustable sling24. The goals of surgical treatment for PPUI are to preserve bladder capacity and compliance, improve urethral strength, and reduce urinary leakage; the choice of treatment depends on the severity, duration, and type of symptoms24,25.

For PPUI, a standard strategy for surgical treatment and the choice of surgical procedure have not been established24. However, it is generally accepted that when PPUI persists for more than 12 months, surgical treatment may be considered24. According to the American Urological Association/Society of Urodynamics Female Pelvic Medicine and Urogenital Reconstruction Adult Urodynamics (AUA/SUFU) Guideline (2019) on incontinence after prostate treatment, before performing a prostatectomy, the patient should be fully informed that PPUI may continue and require future treatment. In addition, AUS can be considered for patients with bothersome UI or who have UI after 1 year of conservative treatment; an adjustable or nonadjustable sling can also be considered for patients with mild to moderate UI26.

Considering the limited evidence and guideline recommendations, in this study, a systematic review (SR) and network meta-analysis (NMA) were performed that can help determine the priority for the selection of surgical methods in PPUI among randomized controlled trials (RCTs) and provide fundamental information to design future prospective trials.

Materials and methods

This SR and NMA were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Supplemental Digital Content 7, http://links.lww.com/JS9/A36 extension for NMA of healthcare interventions guidelines and AMSTAR (assessing the methodological quality of systematic reviews) guidelines. Our protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database before the initiation of the study (CRD42022348828). This work was also registered at Research Registry (UIN: reviewregistry1472). This SR and NMA were performed according to the PRISMA, Supplemental Digital Content 1, http://links.lww.com/JS9/A30 extension for NMA of healthcare interventions guidelines27. We also self-evaluated the quality of the SR using AMSTAR 2, Supplemental Digital Content 2, http://links.lww.com/JS9/A31 criteria28.

Data sources and literature searches

We retrieved data from electronic literature searches of PubMed and the Cochrane Library using the MeSH (Medical Subject Headings) terms and text keywords from the earliest available date of indexing through August 2021. The subject headings and text keywords included those related to the population (male patients with UI), interventions and comparisons (no treatment, nonadjustable sling, adjustable sling, injection of urethral bulking agents, and AUS), and outcomes [the number of patients achieving continence, International Consultation on Incontinence Questionnaire (ICIQ) score, pad weight, and 24 hours pad test]. The search terms were grouped according to Boolean operators (AND, OR, NOT). The searches were limited to human studies and were conducted in all languages and study types. The same search strategy was adopted for EMBASE (Excerpta Medica Database) using Emtree (EMBASE subject headings). Additional studies were screened by two independent investigators (J.J.P. and J.H.K.) through a manual search of clinical trial databases and previous study reference lists (Supplementary Table 1, Supplemental Digital Content 3, http://links.lww.com/JS9/A32).

Inclusion and exclusion criteria for study selection

The inclusion criteria for relevant studies were as follows: (1) the study population in RCTs comprised male patients with experience of UI; (2) the interventions and comparisons included the administration of (no treatment, nonadjustable sling, adjustable sling, injection of urethral bulking agents, AUS); (3) outcomes were the number of patients achieving urinary continence, improvement in ICIQ score, pad weight, and pad use count. Duplicate publications, including those that did not contain original data, such as review articles, case reports, conference abstracts, editorials, letters, and guidelines were excluded. Two investigators (J.J.P. and J.H.K.) independently screened the titles and abstracts of all the articles using the predefined inclusion criteria. The investigators then independently examined the full-text articles to determine whether they met the inclusion criteria. Furthermore, the same authors (S.R. Shim and J.H. Kim) independently extracted data using a data extraction form. The final inclusion of each article was determined by the investigators through evaluation and discussion. The references and data for each included study were cross-checked to maintain the integrity of the meta-analysis and the absence of overlapping data.

Data extraction and measurement outcomes

Basic information details regarding the studies (first author, year of publication, country, and follow-up period), study design (prospective, comparative study, and RCT), patient characteristics (number of patients and mean age), and technical aspects were extracted from the included articles, using a predefined data extraction form. For variables, three important variables were included: ICIQ score, which a score of zero means no leakage of urine and no affection on quality of life; pad weight for 24 h; pad use for 24 h. The primary outcomes were the last measurement, in each study, of the continence rate, ICIQ score, pad weight, and pad use count. Only studies that provided complete information were included in the final meta-analysis.

Data analysis

We performed a Bayesian NMA using the R version 4.0.3 ‘gemtc’ package. The random effect model analysis pooled the odds ratios (ORs) and 95% credible intervals (CrIs) using the number of patients achieving urinary continence events and the total number of patients achieving urinary continence, improvement in ICIQ score, pad weight, and pad use count. A two-sided P value of less than 0.05 was considered statistically significant. Publication bias was examined using funnel plots.

To compare the five treatments (no treatment, nonadjustable sling, adjustable sling, injection of urethral bulking agents, and AUS), the prior distribution and likelihood were fed into a Markov chain Monte Carlo simulation, and the distribution with the best convergence of the posterior distribution was chosen. The Markov chain Monte Carlo simulation was used to determine the probability of a stable distribution and the area under the posterior distribution function. Finally, the posterior distribution was used to perform statistical reasoning for the effectiveness of treatment.

We performed node-splitting assessments to determine the association between the direct and indirect evidence for the consistency test. The surface under the cumulative ranking curve (SUCRA) was used to calculate the probability of each index test as the most effective diagnostic method based on a Bayesian approach using probability values to facilitate the interpretation of diagnostic performance; the larger SUCRA value was identified to be associated with the higher rank of the intervention29,30.

Quality assessment

We performed a risk of bias evaluation on the included studies using the RoB 2 tool. The risk of bias arising from the randomization process (D1) was evaluated according to whether the randomization process was randomly assigned, whether the allocation sequence was concealed and whether baseline differences in each group affected the randomization process. The risk of bias due to deviations from the intended intervention (D2) was evaluated according to whether participants perceived the assigned intervention, whether people delivering the intervention perceived the assigned intervention, whether the intended intervention was deviated due to trial context, and whether the effect of the intervention was adequately assessed. Missing outcome data (D3) was evaluated according to whether the outcome was available for all the participants and whether there was no bias due to the missing outcome data. The risk of bias in the measurement of the outcomes (D4) was evaluated according to the appropriateness of the method used to measure the outcome, whether the same measurement method was used between the groups, and whether the evaluator was aware of the intervention. The risk of bias in the selection of the reported result (D5) was evaluated according to the analysis based on a prespecified analysis plan that was finalized before the analysis of the results and whether the results were likely to be selected. For every domain, each study was assessed at all levels and judged to be at either low risk (‘Low’), some concern (‘Some concerns’), or high risk (‘High’) according to a flow chart. The overall risk of bias was low if all domains were at ‘Low,’ some concern if there was at least one domain at ‘Some concerns,’ and high risk if there was even one domain at ‘High.’

Results

Study selection

The initial search identified a total of 105 articles from electronic databases (PubMed, 20; Cochrane, 17; and EMBASE, 68), of which 44 were unrelated to the topic, contained overlapping data, or appeared in more than one database and hence were excluded. After a more detailed review, an additional 23 papers that were review studies or concerned with nontarget diseases were eliminated. After screening the titles and abstracts, 42 studies were found to be eligible for intensive screening. Of these, 28 were further excluded for the following reasons: no target disease (n=8), no target treatment (n=9), no outcome value (n=5), commentary and letter (n=5), and others (n=1). Finally, 11 studies, including 1116 participants, met our selection criteria for NMA (Fig. 1). An SR of the 11 studies was also conducted to assess the detailed experimental differences and subject descriptions (Table 1). Included studies had outcomes of 11 continence rate, 3 ICIQ, 3 pad weight, and 3 pad use count; and NMA was performed for each outcome (Fig. 2, Supplementary Figure 1, Supplemental Digital Content 4, http://links.lww.com/JS9/A33).

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of the study identification and selection process.

Table 1.

Characteristics of the included studies

Studies	Journal	Study type	Study design	Inclusion criteria	Definition of continence	Number of patients	Mean age (SD)	BMI (kg/m²)	Follow-up period (months)
Adjustable sling vs. nonadjustable sling
Chung et al.31	Neurourol Urodyn	RCT	G1: Nonadjustable Advance male sling G2: Adjustable Argus male sling	(1) All male patients who underwent MS surgery between January 2009 and December 2011	Social continence: use 0–1 urinary pad use over 24 h	44 (Argus: 25, Advance: 19)	Argus: 65.4 (47–76) Advance: 63.8 (48–72)	–	Argus: 36.2 (24–48) Advance: 33.1 (24–46)
Lima et al.32	J Urol	RCT	G1 : Advance (nonadjustable) G2 : Argus T (adjustable)	(1) Patients with 50–80 years of age with PPUI for at least the past 6 months, regardless of the level of incontinence	(1) Average number of incontinence episodes over 24 h ≤2 (2) Average pad using ≤1 (3) Pad weight ≤50 g (4) ICIQ-SF with score reduction ≥80%	22 (Advance: 11, Argus T: 11)	G1: 62.09 (±5.30) G2: 62.55 (±8.54)	–	6, 12, 18 months
Adjustable sling vs. AUS
Esquinas et al.33	Adv Ther	Comparative prospective nonrandomized study (IDEAL, phase IIa)	G1: ATOMS G2: AUS	(1) Stress incontinence after prostate surgery (2) Refractory to conservative options for <1 year *Patients with post-prostatectomy incontinence	Total dryness (a) patients without pads (b) using a safety pad/day with <10 ml in the pad test Social continence: 1–2 pads/day regardless of the pad test results	129 (ATOMS: 102, AUS: 27)	ATOMS: 69.0±6.1 AUS: 70.1±6	ATOMS: 27.1±3.9 AUS: 29.7±4	34.9±15.9
Tuygun et al.34	Urology	Comparative study	G1: Adjustable bulbourethral male sling G2: AUS	Patients with recurrent post-prostatectomy incontinence who had undergone either adjustable bulbourethral male sling placement or AUS implantation	Cured: 0 pad Improvement: no more than 2 pads	16 (male sling: 8, AUS: 8)	G1: 70 (68–74) G2: 69 (65–72)	–	G1: 10 (7–19) G2: 22 (6–38)
Nonadjustable sling vs. AUS
Abrams et al.35	Eur Urol	Noninferiority RCT	No-blinded G1: Male transobturator sling G2: AUS	(1) No previous male sling or AUS surgery (2) Resolved bladder neck contracture or urethral stricture after prostate surgery (3) Sufficient manual dexterity to operate the AUS device (4) Able to give informed consent or complete trial documentation	The definition of incontinent is a participant who has indicated any frequency other than ‘never’ or an amount greater than ‘none’	380 (Male sling: 190, AUS: 190)	Male sling: 68 (64, 71) AUS: 69 (63, 72)	–	12
Sacco et al.36	BJU Int	Comparative study	G1: AUS G2: RTS	(1) Stress-predominant PPI of moderate degree at the time of the continence procedure (2) Radical prostatectomy as the cause of PPI (3) Implantation of TiLOOP male sling or AMS800 with InhibiZone (4) 12 months of follow-up	Cured: 0, 0 or 1 dry ‘safety’ pad, 0–1 pad/day	109 (AUS: 51, sling: 58)	AUS: 71 (66–76) RTS: 70 (66–74)	AUS: 28 (27–29) RTS: 28 (26–30)	6, 12, last follow-up
Nonadjustable sling vs. no treatment
Bahler et al.37	J Urol	RCT	Single-blind (patient) IG: Patients with a SIS sling CG: Patients without a SIS sling (All: Undergoing robot-assisted radical prostatectomy) SIS: small intestinal submucosa	Patients undergoing RARP with or without SIS bladder neck sling placement	Urinary continence: 0–1 pad/day	147 (IG: 73, CG: 74)	IG: 60.9±6.1 CG: 60.6±7.1	IG: 29.4±4.7 CG: 30.0±5.6	1, 3, 6, 12
Altinova et al.38	Urology	RCT	G1: RRP + rectus fascial sling G2: RRP	Patients underwent RRP for clinically localized prostate cancer *A rectus fascial sling procedure was incorporated into RRP	Fully continent: no use of pads Mild incontinence: 1 or ≤1 pad/day	86 (G1: 40, G2: 46)	G1: 63.2±8.5 (35–76) G2: 63.7±6.0 (51–74)	–	12
AUS vs. injection
Imamoglu et al.39	Eur Urol	RCT	G1: Minimal incontinence G2: Total incontinence *Minimal incontinence definition (a) Total number of pads ≤2 (b) Total weight of pads ≤100 g (c) Score of quality of life scale ≤30	(1) Patients who have complaints of incontinence despite conservative treatment (Kegel exercises, imipramine) following RRP or TURP/TVP lasting a year or 6 months, respectively	Dry: use no pad Social continence: use less than 1 pad	G1: 21 (AUS: 11, injection: 10) G2: 24 (AUS: 11, injection: 13)	AUS: 64 (52–76) Injection: 62 (55–75)	–	AUS: 60 (8–120) Injection: 48 (6–84)
Kuznetsov et al.40	Urology	Comparative study	G1: AUS G2: Collagen	(1) Patient who had undergone either transurethral collagen injections or placement of an AUS for post-prostatectomy incontinence	Dry: 0 pad Social continence: ≤1 pad/day	77 (AUS: 36, Collagen: 41)	–	–	19 months
AUS vs. no treatment
Fleshner et al.41	J Urol	Comparative study	IG: AUS CG: No need AUS *Both underwent radical prostatectomy	(a) Underwent radical prostatectomy at our institution (b) had urinary symptoms *Control group: undergo radical prostatectomy at least 1 year	–	61 (IG: 30, CG: 31)	IG: 69 (55–78) CG: 67 (45–75)	–	IG: 39 (9–149) CG: 46.7(13.6–112.4)

ATOMS, adjustable transobturator male system; AUS, artificial urethral sphincter; CG, control group; ICIQ-SF, International Consultation on Incontinence Questionnaire-Short Form; IDEAL, ideal, development, exploration, assessment, long-term follow up; IG, intervention group; MS, male sling; PPI, post-prostatectomy incontinence; PPUI, post-prostatectomy urinary incontinence; RARP, robot-assisted radical prostatectomy; RCT, randomized controlled trial; RPP, radical retropubic prostatectomy; RTS, retrourethral transobturator sling; TURP, transurethral resection of the prostate; TVP, transvesical prostatectomy.

Figure 2.

Network plot (continence rate). AUS, artificial urethral sphincter.

Quality assessment

We evaluated the 11 PPUI studies using the five RoB 2 domains to determine the risk of bias. In D1, five studies were classified as ‘Some concerns.’ In D2 and D3, all 11 studies were classified as ‘Low.’ In D4, 1 study (Altinova et al.,38) was classified as ‘Low’ and 10 studies as ‘Some concerns.’ In D5, all studies were classified as ‘Low.’ Based on these evaluations, the overall risk of bias was ranked. Ten studies were classified as ‘Some concerns’ and one study as ‘Low’ (Fig. 3). We also evaluated the quality using AMSTAR 2, Supplemental Digital Content 2, http://links.lww.com/JS9/A31, which revealed high quality.

Figure 3.

RoB 2 traffic light plot.

Outcomes

A total of 1116 patients from 11 direct comparison trials were included (12 effect sizes with five treatments) in the study. AUS had the highest continence rate in the NMA. The pooled overall ORs of patients achieving urinary continence compared with no treatment was 3.31 (95% CrI: 0.749, 15.710) in AUS, 2.97 (95% CrI: 0.412, 16.000) in adjustable sling, 2.33 (95% CrI: 0.559, 8.290) in nonadjustable sling, and 0.26 (95% CrI: 0.025, 2.500) in the injection of urethral bulking agents (Fig. 4A). A total of 342 patients from three direct comparison trials were included (three effect sizes with three treatments). The pooled overall ICIQ score of patients compared with nonadjustable sling was −5.62 (95% CrI: −19.900, 7.530) in AUS and 2.07 (95% CrI: −12.300, 15.800) in adjustable sling (Fig. 4B). A total of 167 patients from three direct comparison trials were included (three effect sizes with three treatments). The pooled overall pad weight of patients compared with nonadjustable sling was −950.00 (95% CrI: −1810.000, −92.500) in AUS and −517.00 (95% CrI: −1290.000, 257.000) in adjustable sling (Fig. 4C). A total of 441 patients from three direct comparison trials were included (three effect sizes with three treatments). The pooled overall pad use count of patients compared with a nonadjustable sling was −0.300 (95% CrI: −5.330, 4.660) in AUS and 2.15 (95% CrI: −3.710, 8.610) in an adjustable sling (Fig. 4D).

Figure 4.

Forest plot: (A) continence rate, (B) International Consultation on Incontinence Questionnaire, (C) pad weight, and (D) pad count. AUS, artificial urethral sphincter; CrI, credible interval.

Figure 5 shows the SUCRA values of ranking probabilities for each treatment performance, which indicated that AUS ranked first in terms of continence rate, ICIQ, pad weight, and pad use count. Symmetric funnel plots showed that there was no evidence of publication bias in this NMA (Supplementary Figure 2, Supplemental Digital Content 5, http://links.lww.com/JS9/A34).

Figure 5.

Surface under the cumulative ranking curve plot: (A) continence rate, (B) International Consultation on Incontinence Questionnaire, (C) pad weight, and (D) pad count. AUS, artificial urethral sphincter; NMA, network meta-analysis.

Inconsistency test

The inconsistency tests for NMA assumption were analyzed using the node-splitting method, and the results indicated consistency among the direct and indirect evidence of all outcomes. Therefore, a consistency model was applied in the current study (all P>0.05).

Publication bias

The statistical approaches for the detection of publication bias or a small-study effect in 14 studies are shown in Supplementary Figure 1, Supplemental Digital Content 4, http://links.lww.com/JS9/A33. Egger’s regression (two-tailed P=0.232) and a visual inspection of the symmetry graphic in the funnel plot suggested that there was no evidence of publication bias or small-study effect in this NMA.

Discussions

To the best of our knowledge, this study is the first NMA performed to directly compare the effectiveness of surgical treatments for UI after prostate surgery. In the present study, an NMA was performed on various outcomes including continence rate, ICIQ score, pad weight, and pad count. The results of this study suggested that only AUS had a statistically significant effect compared to the nonadjustable sling group and the highest PPUI treatment effect ranking among other surgical treatments.

Considering the prevalence of PPUI (6.3–52%) in BPH and PCa, PPUI is suggested as a significant factor that decreases a patients’ quality of life and causes an economic burden4,19,20. PPUI, a common complication in BPH patients who have received TURP or HoLEP and other laser techniques, is usually caused by damage to the proximal part of the rhabdosphincter, distal to the seminal colliculus9,42. The incidence rate of PPUI in BPH is 1.8–8.8%, the prevalence rate of transient PPUI, which resolves within 1 year is 7%, and the incidence rate of permanent PPUI is 1.3%13,43. Several studies have reported the prevalence of PPUI in patients with PCa as 4–30%, according to the definition of PPUI used44. Furthermore, in one meta-analysis comparing the surgical modality, the prevalence of PPUI 1 year after surgery was statistically significantly lower in the RALP group than in the laparoscopic RP group45. However, in several other studies, the prevalence of PPUI after prostate surgery was reported to vary from 4 to 30% according to the definition of UI, which was used differently depending on the study44,46. For example, PPUI is classified as mild, moderate, and severe according to the severity of symptoms. The prevalence is presented in various ways depending on how PPUI is defined [defined as PPUI requiring treatment (moderate UI or greater) or PPUI not achieving complete dryness (mild UI or greater)]24.

Because the definition of PPUI is ambiguous, the studies included in this NMA used various outcomes. The outcomes used included the number of patients achieving continence, ICIQ score, weight of pads used per day, and the number of pads used per day. In this study, a quality assessment of the included studies was performed, but the evaluation results were limited because blinding was not performed due to the nature of the surgical study.

The AUS was developed in the 1970s and is considered the gold standard for PPUI treatment. Since then, few technological improvements have been made in the treatment47,48. AUS is composed of a reservoir, inflatable cuff, pump, and resistor and works on the principle that the patient inflates the device when required47,49. The treatment success rate of AUS for PPUI has been reported to be high (∼79%), and possible complications include UI due to poor bladder compliance, urethral atrophy, device erosion, and infection50,51. In our study, AUS showed a statistically significant effect compared to the nonadjustable sling group and did not show a statistically significant effect compared to the nontreatment group. However, by additional analysis using the frequentist method, AUS showed statistically significant effect compared to the nontreatment group (Supplementary Figure 3, Supplemental Digital Content 6, http://links.lww.com/JS9/A35).

Although AUS placement has been considered the standard management for severe UI, slings are less invasive and safer; therefore, they should be considered as a possible treatment option before AUS implementation24,25. Slings have been introduced for the treatment of mild UI in males52. Slings are less prone to mechanical failure compared to AUS, and the treatment success rate has been reported to be 40–90%, depending on the device51,52. Slings are divided into adjustable and nonadjustable. The advantage of the adjustable sling is that it can control urethral compression by adjusting the tension of the tape according to the degree of incontinence24,53. Possible side effects of slings include urinary retention, operation site pain, tape erosion, and infection51.

Compared with other surgical treatments, bulking agent injection has the advantage of being less invasive and easy to change to another option, if necessary. The disadvantage is that the treatment success rate is low, and multiple injections are required. A bulking agent is injected into the lamina propria to dissect between the mucosa and muscle layer, thereby dilating the urethra and resulting in a sealing effect54,55.

This NMA includes studies comparing the effects of adjustable slings, nonadjustable slings, AUS, and injection of bulking agents. The included studies were two studies on the comparison between the adjustable sling and nonadjustable sling, two studies on the comparison between adjustable sling and AUS, two studies on the comparison between nonadjustable sling and AUS, two studies on the comparison between the nonadjustable sling and no treatment group, two studies on the comparison between AUS and injection of urethral bulking agents, two studies on the comparison between AUS and no treatment group, and one paper on the comparison between AUS and no treatment group. This NMA compared the treatment effect on PPUI of each modality compared to the no treatment group. The pooled overall ORs of patients achieving urinary continence were 3.31 (95% CrI: 0.749, 15.710) in AUS, 2.97 (95% CrI: 0.412, 16.000) in adjustable sling, 2.33 (95% CrI: 0.559, 8.290) in nonadjustable sling, and 0.26 (95% CrI: 0.025, 2.500) in the injection of urethral bulking agents.

In a study by Chung et al.31 on the comparison between the outcomes of adjustable and nonadjustable slings in men who underwent male sling surgery, no statistically significant difference was reported in the rate of achieving social continence and satisfaction. On the other hand, Lima et al.32 compared the effects of adjustable slings and nonadjustable slings in patients with PPUI and showed a statistically significant improvement in satisfaction and a 24-hour pad test in the group that received an adjustable sling. A study by Esquinas et al.33 on the comparison between the effects of AUS and adjustable slings in patients with PPUI showed significant improvement in a pad test and ICIQ-Short Form in the AUS group, but the total dryness, social continence, and satisfaction were similar. Both studies, comparing the effects of nonadjustable slings and AUS, showed improvement in pad tests or the rate of achieving continence in the group receiving AUS, but a statistically significant difference was only reported in the study by Sacco et al.35,36. In Imamoglu et al.’s study39 on the comparison between the effects of AUS and Macroplastique injection in patients with PPUI, the treatment effect was analyzed by classifying the patients into a minimal incontinence group and a total incontinence group. In the minimal incontinence group, there was no statistically significant difference in the effects of the two treatment options, but in the total incontinence group, AUS showed significant improvement in pad tests and quality of life.

As mentioned above, it is assumed that uniformity in the definition of clinically important PPUI should be specified. The clinically important definition of PPUI is suggested as a case in which surgical treatment is actually required. The following supplements are needed when designing a prospective study to be conducted in the future, based on the results of the present study. A unified definition of UI should be used and objective outcomes should be presented. Hence, it is recommended to perform a pad count and ICIQ score at the same time, and a study design that can obtain long-term follow-up results is required. This aspect is also considered a strength of our study as it suggests improvements that are necessitated for additional studies.

This study has several limitations. First, the number of studies included is small. Therefore, it is necessary to conduct a study with a larger number of samples based on the results of the present study. However, while existing studies are RCTs, this study is meaningful as it is the first meta-analysis. Second, there is methodological heterogeneity in the study caused by factors such as inconsistent outcomes when evaluating the effect of each treatment option used. To overcome this limitation, NMA was performed using several outcomes, such as the number of patients who achieved continence (continence rate), ICIQ, pad weight, and pad count. In addition, the ambiguity of the definition was supplemented by using outcomes with a follow-up period of 12 months or longer. Later, more accurate results can be obtained if standardization of symptom definitions and evaluation indicators are suggested through future research. Next, we dealt with two diseases simultaneously. BPH and PCa are different diseases, but the mechanisms of PPUI are similar. A study currently exists that includes both diseases concurrently39. Finally, the complications of surgical treatments such as AUS or slings have not been sufficiently discussed. This aspect should be supplemented through further studies. There are several RCTs in the studies so far, but the evidence is insufficient due to the small number of trials. More research should be conducted to achieve evidence-based therapeutic decision-making.

Conclusions

The results of this study suggest that only AUS demonstrated a statistically significant effect compared to the nonadjustable sling and had the highest PPUI treatment effect ranking among other surgical treatments. However, well-designed prospective studies with a larger patient population are needed to confirm the results.

Ethical approval

This article does not contain any studies with human participants performed by the author.

Sources of funding

This work was supported by the Soonchunhyang University Research Fund.

Author contribution

S.R.S. and J.H.K.: project development and data analysis; A.K. and Y.J.H.: data collection or management; J.J.P. and J.H.K.: manuscript writing. All authors were involved in manuscript editing and review.

Conflicts of interest disclosure

None of the authors have potential conflicts of interest to declare in relation to the manuscript.

Research registration unique identifying number (UIN)

1.Name of the registry: Prospero.

2.Unique identifying number or registration ID: CRD42022348828.

3.Hyperlink to your specific registration (must be publicly accessible and will be checked): https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=348828

Guarantor

Sung Ryul Shim, PhD, Department of Biomedical Informatics, CHA University of Medicine, Seongnam, Republic of Korea; Institute for Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam, Korea. Tel: +82 1577 4488. E-mail: sungryul.shim@gmail.com.

Jae Heon Kim, MD, PhD, Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University Medical College, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea. Tel: +82 2709 9378, fax: +82 2710 3190. E-mail: piacekjh@hanmail.net.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Supplementary Material

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