Systematic review and meta-analysis comparing Adjustable Transobturator Male System (ATOMS) and Adjustable Continence Therapy (ProACT) for male stress incontinence.

BACKGROUND AND
PURPOSE: Urinary incontinence is one of the most serious complications of prostate cancer treatment. The objective of this study was to assess efficacy and safety of Adjustable Transobturator Male System (ATOMS) compared to Adjustable Continence Therapy (proACT) for male stress urinary incotinence according to literature findings.
MATERIAL AND METHODS: A systematic review and meta-analysis on adjustable devices ATOMS and ProACT is presented. Studies on female or neurogenic incontinence were excluded. Differences between ATOMS and proACT in primary objective: dryness status (no-pad or one safety pad/day) after initial device adjustment, and in secondary objectives: improvement, satisfaction, complications and device durability, were estimated using random-effect model. Statistical heterogeneity among studies included in the meta-analysis was assessed using tau2, Higgins´s I2 statistics and Cochran´s Q test.
RESULTS: Combined data of 41 observational studies with 3059 patients showed higher dryness (68 vs. 55%; p = .01) and improvement (91 vs. 80%; p = .007) rate for ATOMS than ProACT. Mean pad-count (-4 vs. -2.5 pads/day; p = .005) and pad-test decrease (-425.7 vs. -211.4 cc; p < .0001) were also significantly lower. Satisfaction was higher for ATOMS (87 vs. 56%; p = .002) and explant rate was higher for proACT (5 vs. 24%; p < .0001). Complication rate for ProACT was also higher, but not statistically significant (17 vs. 26%; p = .07). Mean follow-up was 25.7 months, lower for ATOMS than ProACT (20.8 vs. 30.6 months; p = .02). The rate of working devices favoured ATOMS at 1-year (92 vs. 76; p < .0001), 2-years (85 vs. 61%; p = .0008) and 3-years (81 vs. 58%; p = .0001). Significant heterogeneity was evidenced, due to variable incontinence severity baseline, difficulties for a common reporting of complications, different number of adjustments and time of follow-up and absence of randomized studies.
CONCLUSIONS: Despite the limitations that studies available are exclusively descriptive and the follow-up is limited, literature findings confirm ATOMS is more efficacious, with higher patient satisfaction and better durability than ProACT to treat male stress incontinence.

Introduction

Urinary incontinence can severely impact the quality of life of prostate cancer survivors after radical prostatectomy and/or radiotherapy [1,2]. The artificial urinary sphincter (AUS) has been the main therapy after failed conservative treatment but reposition of the posterior urethra using retrobulbar slings has been a great revolution [3]. Also development of new devices usig postoperative adjustment has allowed a more personalized approach. Systematic reviews on the topic tend to annalyze a variety of devices with different modes of action [4-7].

Adjustable continence therapy (ProACT®, Uromedica, Minneapolis, MN) using balloons placed periurethraly near the bladder neck was the first adjustable implant to treat stress incontinence. It consists of two volume-adjustable balloons, that increase urethral resistance during voiding. Adjustable transobturator male system (ATOMS®, A.M.I., Feldkirch, Austria) is another adjustable device that compresses the bulbar urethra ventrally but, unlike ProACT, its two-arm mesh allows firm transobturator fixation on both sides of the ischio-pubic bone. Both devices can be adjusted postoperatively without need for aneasthesia. Besides, they open a new perspective of treatment for patients with cognitive impairment and/or limited dexterity, as no manipulation is needed for voiding [8]. Unfortunately, prospective controlled studies comparing anti-incontinence devices are lacking [9].

ATOMS and ProACT share two important peculiarities. Their mode of action is through urethral compression, and both are easily adjusted postoperatively by percutaneous injection of sterile saline solution until continence or a maximun filling volume is accomplished. Their main differences stand in that compression is ventral in ATOMS and lateral (both sides) in ProACT, and also that ATOMS is fixed to the pelvis while ProACT is a non-fixed device. ProACT has longer been used as its first description for male stress incontinence was in 2005 [10] and ATOMS started in 2011 [8]. ProACT remains unchanged but several modifications have been undertaken in ATOMS port location and design, evolving from inguinal to scrotal and silicone-covered.

Randomized comparative studies between ProACT or ATOMS have not been performed to date but a number of individual or multi-center studies with same or very similar endpoints covered are available for both devices. With this study we aim to evaluate the current evidence on the efficacy and safety ATOMS compared to ProACT using a systematic review approach and meta-analysis.

Materials and methods

A systematic review of the scientific literature was carried out in September 2019. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist is included (). The search included studies published between January 2005 and August 2019. The search was undertaken in PubMed, Embase, Web of Science and Scopus. Search strategy was designed according to PICOS criteria (Population, Intervention, Comparator, Outcomes and Study Design) () for the identification of studies using free and controlled terminology. Search strategy included the terms: “Urinary incontinence” AND “male” AND “ATOMS” OR “ProACT”. A manual revision of the bibliographic references was also carried out. We included prospective and retrospective, multi-centre or single-centre case series, published in English, Spanish, German or Italian on patients treated with ATOMS or ProACT devices for SUI after prostate surgery. No clinical trial on the topic could be found. Duplicate studies, editorial comments, letters to the editor or expert opinions in non-systematic reviews, a report after cystoprostatectomy and a meta-analysis centered only on ATOMS were excluded.

The identification, selection and extraction of data from the studies were carried out exhaustively and independently by two reviewers. A first selection of the studies was performed by reading the title and the abstract, and those that met the inclusion criteria were reviewed by reading the full text. Disagreements were resolved by consensus or in collaboration with another member of the research team. Consecutive publications from the same groups were evaluated to avoid overlapping of patients in different studies. Whenever repetition was detected we only used the last publication with larger number of patients. The evidence was summarized with the data extracted from the studies that included bibliographic information, characteristics of the study and patients, characteristics of the intervention, and outcome measures in relation to the efficacy and safety of the procedure. The definitions of postoperative dryness and improvement were comparable among studies. Differential pad-count or differential 24h pad-test was calculated as after adjustment minus baseline when available, assuming both values are non-dependent. Safety was defined according to rate of explantation and complications.

Primary efficacy indicator was percentage of dry patients after adjustment, defined as patients using no pad or only one safety pad/day (PPD). When dry rate change evolution in time was described in a study only the initial report was used. Main secondary efficacy outcome was percentage of overall improvement (defined as ≥50% decrease in pad-count and/or in 24h pad-test). Differential pad-count and differential 24h pad-test between baseline and after adjustment were investigated to evaluate the magnitude effect. The proportion of patients satisfied with the intervention, complication rate, explantation rate, number of adjustments, follow-up after implantation and durability of the devices were also evaluated as secondary outcomes. We also included an analysis of manuscript quality assessment using the Newcastle-Ottawa scale.

The heterogeneity assumption was evaluated by the chi-square-based Cochran’s Q test (which was considered significant at p-value < .05), and quantified with the I2 statistic (with values <25%, 25% to 75%, and >75% interpreted as representing low, moderate and high levels of heterogeneity, respectively), and with tau2 (the between-study variance) that was obtained with the DerSimonian and Laird method. Due to the presence of heterogeneity, random-effects model with the inverse variance method was used for pooling of single proportions, single means or mean differences from primary studies. The pooled effect was described with 95% confidence interval (CI). Publication bias was assessed by visual inspection of funnel plots and quantified by the Egger's linear regression test. Statistical analysis and figures were performed with the meta package of R software version 3.4.1 (R Foundation for Statistical Computing, Vienna, Austria) [11].

Results

Literature search

The search initially provided 174 references, 61 of which dealt with the topic evaluated. Additional records identified 6 further references through other sources. The reason for exclusion was multiple. Three studies were duplicated and 13 were not considered eligible (11 did not meet inclusion criteria and 2 were previous non-updated meta-analysis). Besides, 10 full-text articles were excluded for several reasons: 2 described the operative technique and urodynamic data but did not provide information to be included, 1 used different devices simultaneously, 1 was a case report with an unusual complication, 3 were pilot studies published before the definite article included and 3 were post-hoc studies of primary reports already included that focused on specific results (patient reported outcomes, stratification of results according to different generation of devices and a subgroup of patients with longer follow-up) ().

Characteristics of the studies

Tables and show the characteristics of the 41 selected studies, published between 2005 and 2019, that include 3059 patients in total. Twenty-one articles were published using ProACT [12-32] and 20 using ATOMS [33-52]. No study was randomized controlled, and there was no comparison reported among these or other devices. The main etiology of incontinence was radical prostatectomy but other causes were included. Also the percentage of radiated patients and the degree of baseline incontinence was variable. Dryness rate and improvement rate were very homogeneously reported among the studies. The proportion of patients self-considering satisfied with the device was also often specified; however, 24-h pad-count and, more interestingly, pad-test (baseline, after adjustment and differential) was absent in some studies. The Freeman-Tukey arcsine transform was developed () and pooled proportion (dryness, improvement, satisfaction, explant and complication rates) and mean (number of fillings, differential pad-count and differential pad-test) with 95% confidence intervals were used as summary effect measure.

Tables and summarize the different domains to evaluate study quality. Observational cohorts available have been analyzed according to the Newcastle-Ottawa Scale for quality assessment. None of the studies included in this meta-analysis was a randomized clinical trial and studies generally lack a nonexposed cohort or control. However, the comparision of the intervention is possible with respects to baseline situation before use of device. Attrition bias seems low and the cohorts appear comparable for outcome assessment.

Baseline characteristics

Similarities between the populations evaluated for each device were investigated to confirm the groups are comparable. Firstly, regarding baseline incontinence severity baseline pad-count for ATOMS and ProACT were equivalent (5.05 (95% CI 4.8;5.3) PPD compared to 4.6 (95% CI 3.9;5.3) PPD; p = .27). Secondly, the proportion of patients with previous surgery for incontinence was similar between devices (16.1% (95% CI 9.7;23.5) for ATOMS vs. 11% (95% CI 5.05;18.6) for ProACT; p = .29). Finally, patient age at the time of surgery was higher for ATOMS (70.8 (95% CI 69.9;71.6) years vs. 68.9 (95% CI 68.1;69.6); p = .0009), but this difference is not clinically significant.

Efficacy

Regarding the primary outcome, mean dryness rate was higher with ATOMS than ProACT (68% (95% CI 62;73) compared to 55% (95% CI 47;63); p = .01) (). Also regarding the main secondary objective of the study, percentage of overall improvement was also higher for ATOMS than proACT (91% (95% CI 87;94) vs. 80% (95% CI 72;87; p = .007) (). A higher proportion of patients self-declared satisfied with ATOMS as well (87% (95% CI 81;92) vs 56% (95% CI 36;76); p = .002) (). Conversely, mean number of fillings for adjustment was lower for ATOMS than proACT (2.4 (95% CI 1.9;2.9) vs. 3.5 (95% CI 3;3.9); p = .001) ().

Results revealing the magnitude of effect for improving urine loss are quantitatively notorious. Mean baseline pad-count was equivalent in the studies evaluated (5 PPD (95% CI 4.8;5.3) for ATOMS and 4.6 PPD (95% CI 3.9;5.3) for proACT; p = .27) but postoperative pad-count was lower for ATOMS (1.1 PPD (95% CI .9;1.3) vs. 2.1 PPD (95% CI 1.7;2.5); p < .0001). Therefore, mean differential pad-count was also lower for ATOMS (-4 PPD (95% CI -4.4;-3.7) vs. -2.5 PPD (95% CI (3.5;-1.5); p = .005) (). Studies revealing mean pad-test were less numerous, especially for proACT; however, interesting data were also evidenced. Mean baseline pad-test reported was significantly higher for ATOMS (505 mL (95% CI 461;549) vs. 312 mL (95% CI 231;394); p < .0001) but postoperative pad-test became equivalent (22 mL (95% CI 13;31) for ATOMS and 91 mL (95% CI 15;186) for ProACT; p < .08). Not strikingly, mean differential pad-test was lower for ATOMS (-426 mL (95% CI -462;-389) vs. -211 mL (95% CI -312;-111); p < .0001) ().

Risk of publication bias was not identified for primary efficacy outcome, and variables evaluating the effect magnitude (differential pad-test and differential pad-count) (). However, significant heterogeneity was detected in all variables evaluated (), what possibly depends on different baseline severity of incontinence and patient profile, use of differrent generation devices for ATOMS and also different technique to appropriately place ProACT as described in the literature. Only randomization could reduce these biases.

Safety and device durability

Mean follow-up was 25.7 months (95% CI 22.7;28.7), lower for ATOMS than ProACT (20.8 months (95% CI 17.1;24.5) vs. 30.6 months (95% CI 23;38.1); p = .02). The studies presented interesting safety results, both on explatation and complications. Mean explant rate was significantly lower for ATOMS (5% (95% CI 2;9) vs. 25% (95% CI 19;31); p < .0001) (). Complication rate was also lower for ATOMS, but without reaching statistical significance (17% (95% CI 13;22) vs. 26% (95% CI 18;34); p = 0.067) (). Similarly, major complication rate was similar between devices 4.2% (95% CI 1.7;7.7) for ATOMS vs. 10.4% (95% CI 3.15;20.7) for ProACT; p = 0.15). Risk of publication bias was not identified for these safety outcomes, but significant heterogeneity was probably related to the variability in reporting complications among studies (),

Only 4 studies reveal strong data on durability (2 for each device) and specific analysis of Kaplan-Meier curves given and number of patients at risk allows to compare the proportio of devices that continue working in place, was higher for ATOMS on 1-year (92% (95% CI 87;96) vs. 76% (95% CI 69;83); p < .0001), 2-years (85% (95% CI 74;93) vs. 61% (95% CI 52;70); p = .0008) and 3-years (81% (95% CI 73;87) vs. 58% (95% CI 48;67); p < .0001) ().

Forest plot of studies analyzed with durability of the devices at 12-months (A), 24-months (B) and 36-months (C).

Discussion

Despite male SUI therapy is an area of increasing interest the overall risk of bias must be reported as the majority of studies available about all male incontinence devices including AUS, slings and adjustable devices are retrospective or quasi prospective and mostly single center uncontrolled cohorts. In the absence of randomized controlled trials systematic reviews and meta-analysis can provide better evidence than simple prospective cohorts. Even though, systematic reviews on the topic are scarce and confusing as tend to compile multiple devices with very different mode of action [4]. Also reviews are often biased to compare AUS and other devices, sometimes all named under the misleading term “slings”. Adjustable slings developed to achieve urethral tensioning and results can be satisfactory even in severe incontinence and/or previous irradiation. However, current evidence is not firm to consider they are more efficacious than fixed male slings [6,7].

Both ProACT and ATOMS are really adjustable devices and unlike the AUS exert a non-circumferential periurethral compression that can be increased postoperatively in an office-based setting without re-intervention. The patient carries out urination without manipulation and the risk of mechanical failure is minimal, due to simplicity. Recent systematic reviews and meta-analysis confirm both ATOMS and ProACT are efficacious and safe alternatives to treat male stress incontinence of different degree but provide no comparison between them [53,54]. Interestingly, individual data reported for each device in those meta-analysis is very consistent with data here presented.

ATOMS has been implanted in Europe for a decade. It is used in mild and moderate-to-severe SUI, also in patients with previous radiotherapy. However, results are better in non-radiated patients and non-severe SUI [43,47,53]. Factors determinant of best patient perception with ATOMS are postoperative dryness, severe baseline incontinence severity, non-radiation, less pain at discharge and absence of postoperative complications [55]. ProACT has been implanted for two decades in Europe and more recently in the United States, often in outpatient basis under X-ray or transrectal ultrasound guidance. Based on this minimally invasiveness it has been recommended as first-line treatment in non-irradiated patients with mild-to-moderate incontinence [6,54,56], although revision and explantation rates are high [18,27,29,30] because a correct positioning of the balloons is mandatory to achieve good results [21]. Based on our findings, ProACT does not appear to be an ideal device for durable continence or patient satisfaction. Also it is not so minimally invasive procedure as the complication rate, both total and major complications, surmounts that of ATOMS implant. A very recent experience uses ATOMS after retrieval of ProACT and indirectly supports ATOMS is superior to ProACT in the short-term [51]. What is more ATOMS can be used after radiation while ProACT is not recommended in this situation [6,31].

Pooled data in this meta-analysis reveals ATOMS is superior to ProACT in all the items evaluated for efficacy: dryness (68% vs 55%), improvement (91% vs 80%) and patient satisfaction (87% vs 56%). Definitions used as outcome measures are equivalent in most of the series analyzed (Tables and ). The magnitude of effect is also higher for ATOMS than ProACT, regarding both pad-count change (-4 vs -2.5 PPD) and pad-test change (-426 vs -211 mL). Regarding safety, ATOMS is again superior to ProACT with less explant rate (5% vs 24%) and a higher proportion of devices working in place during the first three years of follow-up.

The main limitations of this meta-analysis stand in the short follow-up, especially in the ATOMS arm, and in the very high heterogeneity observed between studies; probably reflecting a variable severity of sphincteric damage included and the absence of controlled randomized studies. Also the critria to report complications appear variable between the studies analyzed. The limitations highlighted are in consonance with the publication bias identified according to Egger’s linear regression. Despite the existing limitations, we consider this meta-analysis can be of great help both for physicians and health care providers.

Conclusion

The decision upon which is the best device to treat male stress incontinence in a particular patient is influenced by patient status, manual dexterity, incontinence severity and previous radiotherapy. According to this systematic review and meta-analysis both the ProACT and the ATOMS system appear efficacious and safe procedures to treat male stress incontinence. However, taking into account the statistical summary of effect size ATOMS is a more efficacious alternative compared to ProACT with higher dryness, improvement and patient satisfaction rates, lower explant rate and higher durability. It must however be noted that the ATOMS studies have shorter follow-up than the ProACT studies.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 Checklist.

(DOC)

Click here for additional data file.

Assessment of the risk of publication bias by means of Egger’s linear regression test for the study outcomes evaluated.

(DOCX)

Click here for additional data file.

Random effect model (proportion estimate, 95% Confidence Interval) and quantifying heterogeneity (I2, p-value) for the study outcomes evaluated.

(DOCX)

Click here for additional data file.

Freeman-Tukey double arcsine transform proportion for dryness (A), improvement (B), satisfaction (C), differential pad-count (D), differential pad-test (E), number of fillings (F), explant (G) and complication (H).

(TIF)

Click here for additional data file.

11 Oct 2019

PONE-D-19-26165

Systematic review and meta-analysis comparing Adjustable Transobturator Male System (ATOMS) and Adjustable Continence Therapy (ProACT) for male stress incontinence.

PLOS ONE

Dear Dr Angulo,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by Nov 25 2019 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Peter F.W.M. Rosier, M.D. PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Additional Editor Comments (if provided):

Dear authors,

In addition to the reviewers comments: Can you add an explanation for 'previous surgery' in the table. The search strategy as is reported in the manuscripts core tekst is fairly specific: have you missed publications because you seached brand names only? and or only "urinary incontinence" (word combination within quotation marks?) and or, preferably: add the search strategy to the supplements. Furthermore have you checked/controlled or corrected (N patients reported) for the fact that some publications may (partially) contain the same patient cohorts? And also; can you limit your discussion and conclusion more to what you found and concluded in your analysis. Comments about future research should be placed in the discussion and the discussion should not include e.g. 'technical' differences; this, as example, has not been the topic of your research. The sentence (discussion) '...current evidence is still low' should be made more specific; the (discussion and) conclusion could/should include a statement about the overall risk of bias in the publications (e.g. the proportion of retrospective or quasi prospective single center uncontrolled cohorts).

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Summary:

This systematic review compares two techniques for non-neurogenic male stress incontinence that can be adjusted post-operatively: ATOMS and ProACT. Efficacy and safety aspects were considered. The study was well performed and the manuscript is well written.

The conclusion was that ATOMS has better efficacy and a lower complication and explantation rate. It must however be noted that the ATOMS studies had a shorter follow-up than the ProACT studies (20.8 vs 30.6 months on average) and that the severity of complications was not described, only the complication rate. ProACT placement is a less invasive procedure than ATOMS placement. This is summarily hinted in the Discussion, but not described quantitatively. Nevertheless, the comparison of ProACT and ATOMS is fairly described.

Comments:

1. There are some typing errors throughout the manuscript, e.g., grupo instead of group. Also, sometimes a word is missing.

2. Results. The authors write: The main etiology of incontinence was prostatectomy but other causes were included. I assume they mean radical prostatectomy (RP) and not Millin or TURP. Can the authors report the percentages of men with RP in both the ATOMS and ProACT group? Are they comparable?

3. The authors write NA in Table 2. This probably means Not Applicable, but I think NR (Not Reported) would be better.

Reviewer #2: The authors present an interesting and important paper on male postprostatectomy incontinence. Two widely used devices are compared in this meta analysis and the results are presented clearely. Since there is only consensus, that the artifical sphincter should be considered gold standard, it ist important to evaluate the other existing devices. Especially since the artifical sphincter is not the ideal solution for every patient.

Minor spelling mistakes in the paper can easily be fixed. Nevertheless, one comment must be allowed. It would be useful and interesting, if not only the putcome parameters, but also patients characteristics would be compared. All studies have provided statistics concerning their patients like age and type of prior operation. Here the authors should show, that there are no significant differences between ProAct and Atoms groups, since this would make the conclusion stronger.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Jan Groen

Reviewer #2: Yes: Sebastian Nestler, UroGate

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

7 Nov 2019

PONE-D-19-26165

Systematic review and meta-analysis comparing Adjustable Transobturator Male System (ATOMS) and Adjustable Continence Therapy (ProACT) for male stress incontinence.

Dear Editors,

First we would like to thank reviewers and academic editors of PLOS ONE for their effort and the recognition of our work. We are very happy to resubmit our improved work after considering all the recommendations given.

This letter ('Response to Reviewers') is uploaded as separate file, together with a marked-up copy of the manuscript highlighting changes made ('Revised Manuscript with Track Changes').

The manuscript meets PLOS ONE's style requirements.

If the manuscript is finally accepted, I would like to make the peer review history publicly available.

RESPONSE TO EDITOR COMMENTS

1. As recommended the protocol has been deposited in protocols.io, and the DOI identifier assigned is: dx.doi.org/10.17504/protocols.io.8x9hxr6

2. As solicited by the Editor the label 'previous surgery' in the table is better specified as proportion of patients with previous surgery for incontinence.

3. The search strategy is specified in lines 102-103 in Material and Methods section. We confirmed we did not miss publications by using brand names or the combination of words "urinary incontinence".

4. We controlled consecutive publications from the same groups to avoid overlapping of patients in different studies. Whenever repetition was detected we only used the last publication with larger number of patients. This concept is important and is now stated in Material and Methods section (lines 115-118).

5. As recommended the discussion and conclusion sections have been limited more to what we found in your analysis. The sentence on comments about future research in the Conclusion section has been omitted. Similarly, in the Discussion section the sentences on the 'technical' differences between the devices has been omitted.

6. The sentence in the Discussion '...current evidence is still low' is made more specific and instead the overall risk of bias is stated as all the studies available are retrospective or quasi prospective single center uncontrolled cohorts (lines 272-274).

7. The editor noticed some minor occurrence(s) of overlapping text with the following previous publication of our group. A meta-analysis based of the outcomes of ATOMS alone, published in Advances and Therapy (https://doi.org/10.1007/s12325-018-0852-4), reference 53. This and another meta-analysis on ProACT (reference 54) have been cited and discussed form the initial writing of this new article. We also paid great attention to avoid any duplicated text outside the Methods section.

8. As requested, we have included additional details in Methods section regarding an analysis of manuscript quality assessment using the Newcastle-Ottawa scale, lines 179-185 and new Table 3.

9. While revising the submission, figure files have been uploaded to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool to ensure that figures meet PLOS requirements.

RESPONSE TO REVIEWERS

Reviewer #1:

Comment # 1. The conclusion was that ATOMS has better efficacy and a lower complication and explantation rate. It must however be noted that the ATOMS studies had a shorter follow-up than the ProACT studies (20.8 vs 30.6 months on average).

Response to Comment #1: This important detail is completed in the conclusion section (lines 330-332).

Comment # 2: The severity of complications was not described, only the complication rate. ProACT placement is a less invasive procedure than ATOMS placement. This is summarily hinted in the Discussion, but not described quantitatively.

Response to Comment #2: The reviewer is right to state that this subject has not been properly addressed in the original version. In this revised version not only complications rate is described, but we have also reviewed and compared the proportion of major complications reported. That is lower in ATOMS than in ProACT, but again this difference did not reach statistical significance. Thereof we cannot conclude that ProACT is a less invasive procedure than ATOMS as described and this new idea is included in the revised version of the manuscript (lines 256-257, lines 302-303).

Comment # 3. There are some typing errors throughout the manuscript.

Response to Comment #3: Some typing errors have been corrected.

Comment # 4. Results. The authors write: The main etiology of incontinence was prostatectomy but other causes were included. I assume they mean radical prostatectomy (RP) and not Millin or TURP. Can the authors report the percentages of men with RP in both the ATOMS and ProACT group? Are they comparable?

Response to Comment #4: Thank you very much for this comment. The reviewer is right as we mean radical prostatectomy when we say prostatectomy. We have corrected that in the manuscript. It would be very interesting to compare the efficacy of devices not only in radical prostatectomy, but also un simple prostatectomy (Millin procedure) or transurethral resection of the prostate (TUR-P). However, that is not possible because most of the articles do not properly mention the proportion of cases derived from one or the other intervention, especially in the ProACT cohorts.

Comment # 5. The authors write NA in Table 2. This probably means Not Applicable, but I think NR (Not Reported) would be better.

Response to Comment # 5. NA is changed by NR (Not Reported) in Table 2.

Reviewer #2:

Comment #1. Minor spelling mistakes in the paper can easily be fixed.

Response to Comment #1: Some spelling mistakes ad minor typing errors have been corrected.

Comment # 2. Not only the outcome parameters, but also patient characteristics would be compared. All studies have provided statistics concerning their patients like age and type of prior operation. Here the authors should show, that there are no significant differences between ProAct and Atoms groups, since this would make the conclusion stronger.

Response to Comment #2: Thank you very much for this comment. The reviewer is right to ask not only to compare outcomes of the different devices, but also similarity between characteristics of the patients treated by one or the other device. Baseline pad-count (the most frequent objective measurement in most publications) is equivalent between cohorts. Patient age is included in new Table 2 for each study. Type of previous incontinence operation is not available for each cohort in the publications, as a variety of options are possible; however, we have analysed the proportion of patients with previous anti-incontinence operation. New pooled analysis of patient age at the time of implant, baseline pad-count and the proportion of patients previously intervened with both techniques are similar in the literature, what confirms cohorts are apt to be compared. As suggested by the reviewer these data are included both in Results section (lines 205-213) and in revised Supplementary material S3 and S4.

Submitted filename: Response to reviewers and editor.docx

Click here for additional data file.

13 Nov 2019

Systematic review and meta-analysis comparing Adjustable Transobturator Male System (ATOMS) and Adjustable Continence Therapy (ProACT) for male stress incontinence.

PONE-D-19-26165R1

Dear Dr. Angulo,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

With kind regards,

Peter F.W.M. Rosier, M.D. PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Maybe you can follow the suggestion of reviewer 1; Q6, to mention the follow up duration in the abstract, I would be in favour of that.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: It would have been my preference to mention the mean follow-up durations not only in the article itself, but also in the abstract.

Reviewer #2: All comments have been adressed, I have no further questions or comments. The paper should be published

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Jan Groen

Reviewer #2: No

21 Nov 2019

PONE-D-19-26165R1

Systematic review and meta-analysis comparing Adjustable Transobturator Male System (ATOMS) and Adjustable Continence Therapy (ProACT) for male stress incontinence.

Dear Dr. Angulo:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Peter F.W.M. Rosier

Academic Editor

PLOS ONE

Table 1

PICOS criteria to guide the systematic review.

Population	Males with mild, moderate or severe stress urinary incontinence after prostate surgery, eithr previously radiated or not and treated primarily or after failure of other surgical devices
Intervention	Placement of ATOMS ® device
Comparison	Placement of ProACT ® device
Outcomes	Primary: Overall dryness rate (no pad or one security pad per day)Secondary: Overall improvement rate, differential pad-count and/or pad-test (after adjustment with respects to baseline), complication rate and durability
Study Design	Retrospective and prospective case series

Table 2

Studies with ProACT included in the meta-analysis and variables evaluated.

Author Year (Reference)	N	Dry rate (%)	Definition of dryness	Improved rate (%)	Number of adjustments	Satisfied rate (%)	Explant rate (%)	Complication rate (%)	Major complication rate (%)	Baselinepad count (PPD)	Postoperative pad count (PPD)	Baselinepad test (mL/day)	Postoperative pad test (mL/day)	Previous surgery for incontinence (%)	Mean age (yrs)	Meanfollow-up (mo)
Hübner & Schlarp 2005 (12)	117	67	0–1 PPD	88	3(1–15)	NR	27.4	46.2	NR	5.6±3.8	2.5±2.5	NR	NR	NR	70(50–89)	13(3–54)
Trigo-Rocha et al 2006 (13)	25	65.2	0–1 PPD	78.2	4.6(1–7)	NR	17.3	NR	NR	4.7±1.7	1.8±1.6	NR	NR	NR	68.6(61–72)	22.4(6–48)
Kocjancic et al 2007 (14)	64	67	0–1 PPD	82	3(0–9)	NR	14	17.2	NR	5.2	3.6±3.3	NR	NR	NR	65.4(25–79)	19.5(12–62)
Lebret et al 2008 (15)	62	30	0 PPD	89	NR	NR	30.6	NR	NR	4.6(1–10)	1.1(0–6)	NR	NR	NR	71.1(52–87)	6
Gilling et al 2008 (16)	37	62	0 PPD	82	3.3(0–7)	NR	13	48.6	16.2	2.8±2	1.6±1.5	NR	NR	NR	69.9(59–79)	51.5(24–60)
Crivellaro et al 2008 (17)	46	68	0–1 PPD	85	3(1–7)	NR	14	NR	NR	5.1	2.5	NR	NR	NR	67(45–82)	19
Martens et al 2009 (18)	29	31%	0–1 PPD	NR	NR	56	44.8	69	27.6	4.8	3.1	NR	NR	NR	65	41
Gregori et al 2010 (19)	79	66.1	0–1 PPD	91.9	3.6(0–14)	NR	NR	10.1	NR	3.5(1–10)	NR	407.5(40–1300)	NR	NR	68(51–82)	25
García-Matres et al 2009 (20)	69	69.8	0–1 PPD	84	3	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR	22(3–48)
Giammò et al 2010 (21)	18	NR	NR	61	3(1–6)	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR	24(12–38)
Rouprêt et al 2011 (22)	128	66.4	0–1 PPD	75	2.3(0–5)	NR	18	25	NR	4.2(1–20)	1.5	NR	NR	10	71(52–87)	56.3(24–95)
Kjaer et al 2012 (23)	114	50	0–1 PPD	80	4(0–14)	53	20.2	20.2	NR	4.75(1–26)	2.25(0–26)	352.5(16–2800)	11(0–3000)	NR	NR	58(1–80)
Crivellaro et al 2012 (24)	42	71	0–1 PPD	92	NR	7	9.5	NR	NR	NR	NR	NR	NR	23.8	65.2(21–80)	12(3–19)
Gatti et al 2012 (25)	28	60.7	0–1 PPD	85.7	NR	NR	28.6	21	NR	NR	NR	NR	NR	NR	NR	NR
Utomo et al 2013 (26)	49	75.5	0–1 PPD	83.7	4	NR	16.3	NR	NR	NR	NR	NR	NR	22.5	NR	NR
Venturino et al 2015 (27)	22	18	0 PPD	82	4.5(0–15)	45	55	NR	NR	5.9(3–12)	3.9(0–12)	242.3(12–1200)	NR	NR	70.2(53–80)	57
Baron et al 2017 (28)	14	57	0–1 PPD	88	NR	77	28	NR	NR	NR	NR	95±130	34±83	100	69(70–79)	34(4–89)
Nash et al 2018 (29)	123	41	90–100% pad-weight reduction	61	NR	NR	24.2	25.2	NR	4.1±2.3	2.8±1.8	399±437	216±322	22.5	69.7±7.9	18
Nestler et al 2019 (30)	134	NR	NR	82.6	NR	NR	52.7	8.2	2.2	6(4–7)	1(1–2)	NR	NR	NR	71(67–75)	26(9–59)
Noordhoff et al 2018 (31)	143	47.4	0–1 PPD	72.9	4(2–6)	88.3	30.1	21.7	NR	3.5±3	1±1	NR	NR	14.7	69(66–73)	46(21–76)
Finazzi Agrò et al 2019 (32)	240	29.6	<8gr pad weight	37.5	3.78(1–10)	66.3	12.5	22.5	7.9	NR	NR	367±145	113±145	7.5	68.3±7.5	NR

PPD: pads per day; mL: mililiter; yrs: years; mo: months; NR: not reported

Table 3

Studies with ATOMS included in the meta-analysis and variables evaluated.

Author Year (Reference)	N	Dry rate (%)	Definition of dryness	Improved rate (%)	Number of adjustments	Satisfied rate (%)	Explant rate (%)	Complication rate (%)	Major complication rate (%)	Baselinepad count (PPD)	Postopertive pad count (PPD)	Baselinepad test (mL/day)	Postoperative pad test (mL/day)	Previous surgery for incontinence (%)	Mean age (yrs)	Meanfollow-up (mo)
Hoda et al 2012 (33)	124	61.6	0–1 PPD	93.8	4.3±1.8	NR	4	8.9	NR	8.8±3.8	1.8±1.2	725±372	NR	NR	71.2±5.5	19.2±2.2
Seweryn et al 2012 (34)	38	60.5	0–1 PPD <15mL	84.2	3.97(0–9)	NR	10.5	NR	15.8	6.78(2–10)	1.36(0–10)	747(230–1600)	115(0–1500)	28.9	70(60–83)	16.9
Hoda et al 2013 (35)	99	63	0–1 PPD <10mL	92	3.8±1.3	NR	4	NR	NR	7.1±2.3	1.3±1.1	681±466	79.7±210	34.3	70.4±6.2	17.8±-1.6
Krause et al 2014 (36)	36	39	0–1 PPD	50	NR	61.8	30.5	44.4	NR	8.33	4.4	NR	NR	30.5	70.4(50–79)	NR
González-Pérez et al 2014 (37)	13	92.3	0 PPD	87.1	NR	100	0	NR	NR	NR	NR	NR	NR	15.4	63(59–87)	16(4–32)
Friedl et al 2016 (38)	34	56	0–1 PPD	88	NR	NR	11.8	17.6	NR	3.5±0.2	1.5±0.3	NR	NR	29.4	70.7(55–83)	5.7±0.5
Mühlstädt et al 2016 (39)	54	48.1	0 PPD	77.7	4.5±-2.3	NR	7.4	25.9	NR	7.7±4.8	1.6±1.7	NR	NR	20.4	67.5 ± 7.3	27.5±18.4
Friedl et al 2016 (40)	62	61.3	0–1 PPD	90	1.5±1.2	NR	14.5	6.45	NR	4(3–5)	1(0–2)	350(300–542)	5(0–135)	27.4	71.3(69–75)	17.7(1.7–55.5)
Hüsch et al 2016 (41)	49	NR	NR	NR	NR	NR	2.0	14.2	2.0	NR	NR	NR	NR	NR	NR	NR
Buresova et al 2017 (42)	35	62.9	0–1 PPD	100	4.3(1–15)	NR	2.9	20	NR	5	1	NR	NR	NR	66.7(51–81)	21.2(3–63)
Friedl et al 2017 (43)	287	64	0–1 PPD <10mL	NR	3(2–4)	NR	19.5	7	2	4(3–5)	1(0–2)	400(300–700)	18(0–105)	NR	70(66–74)	31(10–54)
Friedl et al 2017 (44)	49	57.1	0–1 PPD <10mL	89.7	2±1	NR	19.5	34.7	16.3	4(3–6)	1(0–2)	458(310–630)	10(0–90)	16.3	73 (68–76)	32±8.5
Angulo et al 2017 (45)	34	85.3	0–1 PPD	95	1±3	97	0	14.7	NR	5±3	0±0	510±500	0±15	11.8	70.5(48–79)	18.5±10
Manso et al 2018 (46)	25	64	0–1 PPD	100	1.54±1.3	84	0	NR	4	4.84±2.95	1.6±2.02	NR	NR	12	71.4±6.6	21.56±8.89
Angulo et al 2018 (47)	215	80.5	0–1 PPD <10mL	85,1	1.4±1.9	85.1	3.25	15.3	3.7	3.9±2	0.9±1.5	484±372	63.5±201	5.6	69.7±6.8	24.3±15
Esquinas et al 2018 (48)	60	81.7	0–1 PPD	93.3	1±2	93.2	1.7	18.6	NR	5±3	0±1	465±450	0±20	6.7	72±7	21±22
Angulo et al 2018 (49)	20	75	0–1 PPD	91.5	1±3	80	0	15	NR	4±3	0±1.5	375±-855	10±32.25	10	76.5±9	38.5±19.5
Angulo et al 2018 (50)	30	76.7	0–1 PPD	100	1±1	83.3	3.3	13.3	NR	4±3	0±1	435±393	10±30	100	73±10	21±22
Giammò et al 2019 (51)	52	73.1	0–1 PPD	98.1	1.55±1	NR	0	19	0	4.23(2–8)	NR	412(180–1100)	100(0–440)	57.7	77.7(58–84)	20.1±20.7
Doiron et al 2019 (52)	160	80	0–1 PPD	87.8	2.4	86.3	NR	22.3	4.4	4(3–5)	0.5(0-1-9	NR	NR	16.3	70.5±6.6	9(4.5–13.5)

PPD: pads per day; mL: mililiter; yrs: years; mo: months; NR: not reported

Table 4

Newcastle-Ottawa scale for assessing the quality of cohort studies with ProACT included in the meta-analysis.

	Selection				Comparability(e)	Outcome
Author Year (Reference)	Representativeness of the exposed (interventional cohort) (a)	Selection of the nonexposed cohort (b)	Ascertainment of exposure (intervention) (c)	Incident disease (d)		Assessment of outcome (f)	Length of follow-up (g)	Adequacy of follow-up (h)
Hübner & Schlarp 2005 (12)	A	C	A	A	A	B	A	A
Trigo-Rocha et al 2006 (13)	A	C	A	A	A	B	A	B
Kocjancic et al 2007 (14)	A	C	A	A	A	B	A	A
Lebret et al 2008 (15)	A	C	A	A	A	B	B	A
Gilling et al 2008 (16)	A	C	A	A	A	B	A	A
Crivellaro et al 2008 (17)	A	C	A	A	A	B	A	A
Martens et al 2009 (18)	A	C	A	A	A	B	A	A
Gregori et al 2010 (19)	A	C	A	A	B	D	A	A
García-Matres et al 2009 (20)	A	C	C	A	B	D	A	D
Giammò et al 2010 (21)	A	C	D	A	B	D	A	D
Rouprêt et al 2011 (22)	A	C	A	A	A	B	A	A
Kjaer et al 2012 (23)	A	C	A	A	A	B	A	A
Crivellaro et al 2012 (24)	A	C	A	A	B	C	A	A
Gatti et al 2012 (25)	A	C	D	A	B	D	B	D
Utomo et al 2013 (26)	A	C	D	A	B	D	B	D
Venturino et al 2015 (27)	A	C	A	A	A	B	A	A
Baron et al 2017 (28)	C	C	A	A	A	B	A	A
Nash et al 2018 (29)	A	C	A	A	A	B	A	A
Nestler et al 2018 (30)	A	C	A	A	A	B	A	A
Noordhoff et al 2018 (31)	A	C	A	A	A	B	A	A
Finazzi Agrò et al 2019 (32)	A	C	A	A	A	B	A	A

(a) A, truly representative of the average patient at risk for male stress incontinence; B, somewhat representative of the average patient at risk; C, selected group; D, no description.

(b) A, drawn from the same source as the intervention cohort (concurrent controls); B, drawn from a different source (historical controls); C, no description of the derivation of the nonexposed control

(c) A, secure record; B, structures review; C, written self-report; D, no description.

(d) Demonstration that outcome of interest was not present at the start of the study: A, yes; B, no.

(e) Comparability of cohorts on the basis of the design or analysis: A, study controls for the most important factor (conditioning regimen), B, study controls for any additional factor; C, not carried out or not reported.

(f) A, independent blind assessment; B, record linkage; C, self-report; D, no description.

(g) Was follow-up long enough for outcomes to occur? A, yes; B, no.

(h) A, complete follow-up (all subjects were accounted for); B,Subject lost to follow-up were unlikely to introduce bias because small numbers were lost (>90% had follow-up, or description was provided of those lost); C, follow-up rate <90%, and there was no description of those lost; D, no statement.

Table 5

Newcastle-Ottawa scale for assessing the quality of cohort studies with ATOMS included in the meta-analysis.

	Selection				Comparability(e)	Outcome
Author Year (Reference)	Representativeness of the exposed (interventional cohort) (a)	Selection of the nonexposed cohort (b)	Ascertainment of exposure (intervention) (c)	Incident disease (d)		Assessment of outcome (f)	Length of follow-up (g)	Adequacy of follow-up (h)
Hoda et al 2012 (33)	A	C	A	A	A	B	A	A
Seweryn et al 2012 (34)	A	C	A	A	A	B	A	A
Hoda et al 2013 (35)	A	C	A	A	A	B	A	A
Krause et al 2014 (36)	B	C	A	A	A	C	A	D
González-Pérez et al 2014 (37)	B	C	A	A	B	C	A	A
Friedl et al 2016 (38)	A	C	A	A	A	B	A	A
Mühlstädt et al 2016 (39)	A	C	A	A	A	B	A	A
Friedl et al 2016 (40)	A	C	A	A	A	B	A	A
Hüsch et al 2016 (41)	A	A	A	A	C	B	B	D
Buresova et al 2017 (42)	A	C	A	A	A	B	A	A
Friedl et al 2017 (43)	A	C	A	A	A	B	A	A
Friedl et al 2017 (44)	C	C	B	A	B	B	A	A
Angulo et al 2017 (45)	A	C	A	A	A	B	A	A
Manso et al 2018 (46)	A	C	A	A	A	B	A	A
Angulo et al 2018 (47)	A	C	A	A	A	B	A	A
Esquinas et al 2018 (48)	A	C	A	A	A	B	A	A
Angulo et al 2018 (49)	C	C	A	A	A	B	A	A
Angulo et al 2018 (50)	C	C	A	A	A	B	A	A
Giammò et al 2019 (51)	B	C	A	A	A	B	A	A
Doiron et al 2019 (52)	A	C	A	A	A	B	A	A

(a) A, truly representative of the average patient at risk for male stress incontinence; B, somewhat representative of the average patient at risk; C, selected group; D, no description.

(b) A, drawn from the same source as the intervention cohort (concurrent controls); B, drawn from a different source (historical controls); C, no description of the derivation of the nonexposed control

(c) A, secure record; B, structures review; C, written self-report; D, no description.

(d) Demonstration that outcome of interest was not present at the start of the study: A, yes; B, no.

(e) Comparability of cohorts on the basis of the design or analysis: A, study controls for the most important factor (conditioning regimen), B, study controls for any additional factor; C, not carried out or not reported.

(f) A, independent blind assessment; B, record linkage; C, self-report; D, no description.

(g) Was follow-up long enough for outcomes to occur? A, yes; B, no.

(h) A, complete follow-up (all subjects were accounted for); B,Subject lost to follow-up were unlikely to introduce bias because small numbers were lost (>90% had follow-up, or description was provided of those lost); C, follow-up rate <90%, and there was no description of those lost; D, no statement.