Second-Generation Radiofrequency and Targeted Therapeutic Exercise for Stress Urinary Incontinence Due to Urethral Hypermobility: A Study Protocol

Round 1

Reviewer 1 Report (New Reviewer)

Comments and Suggestions for Authors

The introduction provides a solid overview of SUI, PFMT, and the rationale for RF, and it cites relevant prior work and guidelines. However, it would benefit from a tighter, more current synthesis of the evidence and from more consistent terminology, because “urethral instability,” “urethral hypermobility,” and “bladder neck opening” are used interchangeably in a way that may confuse readers.

The overall research design is appropriate for the question: a three-arm, single-blinded randomized controlled trial with blinded outcome assessment and prospective registration is a strong design for evaluating PFMT, RF, and their combination.

The methods are described in considerable detail, especially randomization, allocation concealment, intervention content, assessment schedule, safety monitoring, and data handling. That said, several points should be clarified or strengthened: the unequal intervention durations across arms may affect expectation effects and should be discussed more explicitly; the statistical plan would be stronger if a mixed-effects longitudinal model were considered instead of relying mainly on repeated-measures ANOVA; and the manuscript contains some internal wording inconsistencies around data confidentiality and identifiers that should be harmonized.

Because this is a study protocol, there are no results to assess yet, so that item is not applicable. The conclusion section is reasonable as a protocol summary, but the wording should remain clearly prospective and avoid implying efficacy before the trial is completed. The current figures appear useful, especially the timeline, but the schedule figure is text-heavy and would benefit from cleaner formatting; I did not see any substantive tables in the provided manuscript extract.

The English is understandable, but there are repeated grammatical and stylistic issues, including awkward phrasing, duplicated wording, and occasional formatting problems. A careful language edit would improve readability and consistency.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report (New Reviewer)

Comments and Suggestions for Authors

The study presents a randomized controlled protocol aiming to compare the effectiveness of intravaginal radiofrequency (RF), pelvic floor muscle training (PFMT), and their combination in the treatment of stress urinary incontinence in women. The topic is clinically relevant and the prospective design represents a strength. However, in its current form, the study has several important methodological and scientific limitations.

There are significant shortcomings in the methodology. In particular, the absence of a proper control group, the lack of a sham/placebo arm, and the unequal duration of interventions weaken the internal validity of the study. These issues considerably limit the reliability and interpretability of the expected results.

The selected primary and secondary outcomes are not sufficiently patient-centered. Surrogate parameters such as pelvic floor muscle strength are emphasized, while clinically meaningful outcomes reflecting real patient benefit are not adequately prioritized.

Some methodological limitations that should be clearly stated in the methodology section appear to be scattered and discussed in a manner closer to the discussion section, which disrupts the structural coherence of the manuscript and may confuse the reader. The extent of these methodological issues represents a major weakness of the study.

The pathophysiological explanations provided are superficial, and the mechanisms underlying RF treatment are not discussed in sufficient depth. Integration with the existing literature is limited and remains largely descriptive.

Furthermore, there is a clear inconsistency between the therapeutic approach proposed by the authors and current clinical guidelines. According to the European Association of Urology (EAU) 2026 guidelines, the role and level of recommendation for RF therapy are not supported to the extent suggested in this manuscript. The authors are strongly encouraged to revise the discussion in line with the most recent EAU guidelines.

Similarly, key references from the International Continence Society (ICS) are not adequately utilized, particularly regarding terminology and conceptual framework in lower urinary tract function. Incorporating ICS standards would improve the scientific rigor of the manuscript.

There are also notable issues related to language and clarity. The manuscript does not fully meet academic writing standards, and some sections are unnecessarily long and repetitive. A comprehensive language editing is required.

Overall, in its current form, the manuscript does not meet the scientific standards expected for a Q2 journal. However, with substantial methodological revisions, alignment with current guidelines, and improvement in language quality, it may be reconsidered. At this stage, a major revision is recommended.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report (New Reviewer)

Comments and Suggestions for Authors

Accept 

Author Response

We sincerely thank you for your thorough review of the revised manuscript and for recommending its acceptance for publication.

We greatly appreciate the time and expertise you dedicated to this process.

Thank you once again for your valuable contribution.

Best regards

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Please see attached

Comments for author File: Comments.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This protocol addresses a clinically relevant question concerning the conservative management of stress urinary incontinence associated with urethral hypermobility and presents an overall structure consistent with a parallel randomized controlled trial. However, the manuscript contains concrete internal inconsistencies and relevant reporting omissions that compromise transparency, reproducibility, and full compliance with SPIRIT recommendations.

            In addition, the Introduction requires further development in several key areas:

            A more detailed explanation of the radiofrequency technique, including its physiological mechanism of action (thermal effect, collagen remodeling, connective tissue response, potential neuromodulatory contribution) and the biological plausibility of its effect on urethral support.

            A more comprehensive synthesis of the available clinical evidence regarding both supervised PFMT and intravaginal radiofrequency, including study designs, magnitude of effect, duration of benefit, and reported adverse events.

            A clearer justification of the comparator and therapeutic positioning in light of current clinical guidelines, particularly regarding conservative management as first-line treatment and the role of adjunctive or alternative therapies.

            Inclusion of socioeconomic burden data (quality of life impact, direct and indirect healthcare costs, productivity loss, access barriers to surgical care) to justify the clinical and public health relevance of exploring alternative or combined therapeutic strategies in this population.

            These elements are currently underdeveloped and should be strengthened to support the scientific rationale of the trial.

Errors and Required Corrections

1. Ultrasound Eligibility Criterion: Use of Non-Equivalent Definitions

In the Eligibility criteria, the manuscript defines:

“bladder neck opening… minimum retrovesical angle of 140° in Valsalva.”

In the Discussion, the population is again described as SUI associated with “bladder neck opening during exertion,” without maintaining the same operational parameter.

Error: Different ultrasound descriptors are used interchangeably without confirming they represent the same measurement construct.

Correction required: A single operational ultrasound variable (exact name, measurement procedure, cutoff value) must be defined and used consistently across the abstract, methods, eligibility criteria, objectives, and trial registration.

2. Radiofrequency Device Inconsistency

In the intervention section, the manuscript reports:

“Capenergy® device (model C500 Urogyne).”

However, other sections (including earlier manuscript versions) reference a different model, and detailed technical specifications (frequency, power, energy per session) are provided.

Error: The device model and technical specifications are not consistently aligned.

Correction required: The manuscript must report a single device model throughout and ensure all technical parameters correspond unequivocally to that model.

3. Chronological Inconsistency in Trial Status

The manuscript states:

“Recruitment will conclude on March 15, 2026.”

“The intervention is set to begin on March, 2025.”

Error: The intervention date precedes the recruitment completion date, creating chronological inconsistency.

Correction required: The trial status section must be revised to ensure temporal coherence between recruitment, intervention, and follow-up.

4. Allocation Concealment: Insufficient Operational Detail

The manuscript states:

“sealed, opaque envelopes, which participants will open…”

Error: The procedure lacks safeguards ensuring strict sequential allocation, tamper-proof protection, and custody control.

Correction required: A detailed operational description of envelope preparation, numbering, custody, sequential opening, and documentation must be included, as well as clarification regarding block randomization or stratification if applicable.

5. Blinding Procedure Not Operationalized

The manuscript indicates that investigators responsible for assessments and statistical analysts will remain blinded.

Error: No procedural description is provided regarding how blinding is maintained, how participants are prevented from revealing allocation, or how unblinding events are handled.

Correction required: The protocol must describe practical procedures to maintain blinding, manage accidental unblinding, and document such events.

6. Primary Outcome Not Explicitly Declared

The manuscript lists multiple outcomes (ultrasound, Oxford scale, manometry, questionnaires) without formally identifying a primary endpoint.

Error: No single primary outcome is clearly designated.

Correction required: The protocol must explicitly define the primary outcome, its main timepoint, and its analytical metric (e.g., change from baseline).

7. Sample Size Calculation Incomplete

The sample size is described as based on a previous investigation and calculated using G*Power (n = 117), but no effect size, standard deviation, or specific outcome is reported.

Error: Essential statistical assumptions are missing.

Correction required: The calculation must include outcome used, expected effect size, variability, and statistical test structure (three-group comparison).

8. Data Management Description Incomplete

The manuscript mentions an electronic database, password protection, confidentiality, and Google Forms for personal data collection.

Error: The full data lifecycle is not described (collection, transfer, pseudonymization, identifier separation, storage, backup, retention, destruction).

Correction required: A dedicated “Data Management” subsection must detail pseudonymization procedures, access control by roles, secure storage, backup policy, audit trail, and data retention/destruction policy.

9. Adverse Events Section Incomplete

The manuscript briefly mentions possible RF adverse effects and that PFMT has no documented adverse effects.

Error: No formal definitions of adverse events (AE/SAE), severity grading, causality assessment, detection method, reporting procedure, or monitoring timeframe are provided.

Correction required: A structured safety section must define AE/SAE, classification criteria, systematic detection method, documentation procedures, and reporting pathways.

10. Non-Adherence Management May Compromise Follow-Up

The text states that <80% attendance will result in cessation of active involvement.

Error: This wording suggests possible discontinuation of outcome assessment.

Correction required: The protocol must clearly state that outcome collection will continue regardless of treatment adherence status.

11. Longitudinal Statistical Model Insufficiently Defined

Repeated-measures ANOVA is proposed for group-by-time interactions.

Error: Assumptions, missing data handling, and justification for longitudinal modeling approach are not described.

Correction required: The primary longitudinal analytical framework must be clearly predefined, including the strategy for handling missing data and sensitivity analyses.

12. Multiplicity Not Addressed

Multiple outcomes and multiple timepoints (15 days, 3, 6, and 12 months) are included.

Error: No strategy for controlling type I error inflation is described.

Correction required: The manuscript must specify the primary contrast and define multiplicity control for secondary/exploratory outcomes.

13. CONSORT Flow Diagram Missing

Error: No participant flow diagram (screening, exclusions, allocation, follow-up, analysis) is included.

Correction required: A CONSORT-compliant flow diagram must be incorporated.

14. RF Intervention Appendix Missing

The PFMT intervention is described in a detailed supplementary file (S2), but no equivalent structured appendix exists for RF.

Error: Intervention reporting is asymmetrical between groups.

Correction required: A structured RF intervention appendix must be included (step-by-step procedure, parameters, quality control, stopping criteria, session recording).

15. Trial Registration Not Clearly Declared as Prospective

Although registration is referenced in the SPIRIT checklist, the manuscript does not clearly state the identifier, date, and prospective nature within the main text.

Error: Registration transparency is incomplete.

Correction required: The Methods and Abstract must explicitly report registration number, date, and confirm prospective registration, ensuring alignment with reported outcomes.

16. Post-Trial Care / Compensation Not Described

The SPIRIT checklist lists ancillary and post-trial care with an incongruent page reference.

Error: No explicit subsection addresses compensation or post-trial care.

Correction required: A subsection must clarify insurance coverage, compensation policy, and post-trial care provisions, or formally state non-applicability with justification.

17. Abstract Structure Not Aligned with Journal Requirements

Error: Abstract headings do not conform to the journal’s required structured format.

Correction required: The abstract must strictly follow the journal’s prescribed heading structure and order. 

18. References Not Adapted to Journal Formatting Requirements

Error: Citation style and/or reference formatting do not fully comply with the journal’s official guidelines (punctuation, journal abbreviations, order, formatting).

Correction required: The entire reference list must be revised according to the journal’s formatting standards.

19. Incorrect Placement of Appendices / Supplementary Material

Error: Appendices are not positioned according to standard editorial structure.

Correction required: Appendices must be placed after the complete reference list, following the journal’s instructions.

20. Trial Registration Timing and Transparency

Error: It is not clearly stated whether the protocol was registered prospectively (i.e., before recruitment began), and the manuscript does not explicitly confirm alignment between the registered protocol and the submitted version.

Correction required: The manuscript must clearly state in both the Abstract and Methods:

The trial registration number.

The exact date of registration.

Confirmation that registration occurred prior to participant enrollment.

Additionally, the authors should confirm that registered outcomes and timepoints fully match those described in the current manuscript.

21. Additional Recommendations to Strengthen the Discussion

Error: The Discussion section remains conceptually limited and does not fully contextualize the intervention within biological, clinical, and healthcare system frameworks.

Correction required: The Discussion should be expanded to:

Elaborate on the biological plausibility of the combined RF + PFMT intervention, clearly distinguishing structural mechanisms (e.g., connective tissue remodeling, collagen response) from neuromuscular adaptations.

Contextualize expected findings in relation to the established effectiveness of supervised PFMT as first-line treatment, clarifying whether RF is positioned as adjunctive, alternative, or sequential therapy.

Discuss potential clinical implications if superiority is demonstrated (impact on conservative management algorithms, reduction of surgical referrals, possible integration into rehabilitation pathways).

Address potential healthcare and economic implications, including accessibility, resource utilization, and cost-effectiveness considerations.

Explicitly acknowledge foreseeable methodological limitations, including the impossibility of double-blinding, unequal intervention duration between groups, expectation/placebo effects, and adherence variability.

 

Comments on the Quality of English Language

Regarding the overall language quality, the manuscript would benefit from professional English language revision prior to publication.

While the text is generally understandable, several issues are evident:

1. Grammatical inconsistencies, particularly in verb tense usage (future vs. present tense in protocol descriptions). As a clinical trial protocol describing planned procedures, the manuscript should consistently use future tense. In several sections, tense shifts occur without justification.
2. Awkward phrasing and non-native constructions, especially in methodological and statistical sections. For example:
   • “Participants will receive the treatment in order to improve pelvic function and health-related quality of life.”
     This phrasing is repetitive and imprecise.
   • “Group-by-time interactions will be examined.”
     This statement is vague and lacks methodological precision.
3. Terminological inconsistencies, including variation in technical expressions. Terms such as “bladder neck opening,” “urethral instability,” and “urethral hypermobility” are used interchangeably without clear operational definitions, which may lead to conceptual ambiguity.
4. Occasional imprecision in academic tone, including overly absolute or informal expressions. For example:
   • “PFMT has no documented adverse effects.”
     This statement is too categorical and should be phrased with greater scientific caution.
   • “The treatment will be halted promptly if any discomfort or pain is reported.”
     The adverb “promptly” is unnecessary in a protocol context and adds an informal tone.
5. Formatting inconsistencies in structured sections, particularly in the abstract and headings, which do not consistently follow the journal’s required format.
6. Stylistic issues affecting readability, including overly long sentences, excessive passive constructions, and minor capitalization inconsistencies in technical terminology.

These issues do not render the manuscript incomprehensible; however, they reduce clarity, precision, and overall scientific presentation. Given that this is a clinical trial protocol requiring methodological exactness, linguistic refinement is recommended to ensure clarity and professional standards consistent with the journal’s expectations.

A thorough revision by a native English scientific editor or professional language editing service is advisable before acceptance.

Reviewer 3 Report

Comments and Suggestions for Authors

Title: Second-generation radiofrequency application and specific therapeutic exercise as a treatment for stress urinary incontinence due to urethral instability. A study protocol.

General Assessment

This manuscript presents the protocol of a three-arm randomized controlled trial investigating the effects of second-generation radiofrequency (RF), pelvic floor muscle training (PFMT), and their combination in women with stress urinary incontinence (SUI) due to urethral instability. The topic is clinically relevant, and the investigation of RF combined with PFMT addresses an area where high-quality randomized evidence remains limited. The inclusion of ultrasound-based functional assessment and long-term follow-up further strengthens the potential contribution of this study. However, several important methodological concerns significantly limit the internal validity and interpretability of the proposed design. These concerns include inconsistencies in eligibility criteria, unequal intervention dosage across groups, insufficient specification of primary and secondary outcomes, and limitations in the statistical analysis plan.

The study has publication potential; however, major methodological revisions are required before it can be considered suitable for publication.

Line 24 vs. Lines 124–125: The abstract defines eligibility as bladder neck opening >90°, whereas the eligibility criteria section specifies a minimum retrovesical angle of 140°. This discrepancy represents a serious protocol inconsistency that directly affects participant selection and study reproducibility. Clarification and harmonization of these criteria are required.

Lines 22–26: The three intervention arms involve substantially unequal treatment exposure:

• PFMT: 16 weeks
• RF: 5 weeks
• RF + PFMT: combined

This creates intervention dose inequality and potential exposure-time bias, particularly when interpreting the superiority of the combined group. The protocol does not explain how differences in treatment duration and therapeutic load will be accounted for analytically. This threatens internal validity and requires methodological justification or adjustment.

Lines 110–116: Although G*Power was used to calculate the required sample size, critical parameters are not reported, including: Assumed effect size, Primary outcome variable used for calculation, Statistical model (e.g., repeated-measures ANOVA), Assumed correlation between repeated measures. For a three-arm longitudinal RCT, these parameters must be explicitly stated in accordance with SPIRIT Item 19. The current description is insufficient to assess the adequacy of the power calculation.

Lines 146–150: Participants open the allocation envelope themselves after baseline assessment. This procedure may compromise allocation concealment and increase the risk of selection bias. Furthermore, the roles related to sequence generation, allocation implementation, and intervention delivery are not clearly separated. The randomization process does not fully align with CONSORT recommendations and requires clarification.

Lines 124–131: The exclusion of participants with previous pelvic surgery may substantially limit external validity, as this represents a clinically relevant subgroup of women with SUI. The rationale for this exclusion criterion should be explicitly justified.

Lines 180–196: The RF protocol is adapted from treatment protocols for genitourinary syndrome of menopause. However, the pathophysiological mechanisms underlying SUI differ from menopausal atrophic changes. The translational rationale for applying this RF protocol to SUI patients requires stronger physiological justification and supporting literature.

Lines 212–214: Primary and secondary outcomes are not clearly differentiated. Pelvic floor muscle strength, urethral stability, HRQoL, and symptom severity are all listed as outcomes without classification.

The protocol must explicitly define:

• Primary outcome
• Secondary outcomes
• Exploratory outcomes

This clarification is required to ensure statistical coherence and to comply with SPIRIT Item 16.

Lines 245–254: The Oxford scale is used for strength assessment; however:

• Inter-rater reliability
• Intra-rater reliability
• Assessor training standardization

are not described. Reliability measures must be reported to strengthen methodological rigor.

Lines 327–331: Participants attending less than 80% of sessions are classified as non-adherent and removed from active participation. However, the protocol states that all randomized participants will be included in the final analysis under an intention-to-treat (ITT) approach. This creates conceptual inconsistency. The strategy for handling non-adherence, dropout, and per-protocol analysis should be clarified.

Lines 333–341: The protocol proposes repeated-measures ANOVA. Given:

• Multiple follow-up time points (baseline, post, 15 days, 3 months, 6 months, 12 months),
• Potential missing data,
• Unequal intervention duration across groups,

a linear mixed-effects model would be more appropriate and robust. Additionally, no method for handling missing data (e.g., multiple imputation, maximum likelihood estimation) is described, which is inconsistent with SPIRIT Item 27c.

Lines 343–347: The recruitment period is stated as February–March 2026, while the intervention start date is March 2025. This chronological inconsistency must be corrected.

Lines 381–382: The absence of a no-treatment control group is justified on ethical grounds; however, alternative designs (e.g., sham RF or minimal-dose comparator) are not discussed. This design decision requires stronger methodological justification.