Beyond curvature: harmonized endpoints and adherence-adjusted analysis in nonsurgical Peyronie’s disease

We sincerely thank Yang and colleagues for their careful reading of our editorial, “Current status of non-surgical treatments for Peyronie’s disease” (1), and for their constructive commentary proposing phenotype-directed endpoints for nonsurgical management (2). We fully agree with their central premise: therapeutic success in Peyronie’s disease (PD) cannot be adequately captured by the change in curvature angle alone. Deformity characteristics, erectile function, sexual quality of life, patient distress, treatment burden, and the fulfillment of individual expectations are all essential components of a comprehensive efficacy assessment. The heterogeneity of endpoints across contemporary PD trials is well documented and remains a principal obstacle to comparative analysis; critical appraisals of the modern intervention literature have highlighted the absence of standardized pre- and post-treatment assessment protocols, substantial inter- and intra-observer variability in curvature measurement, and the lack of an agreed definition of what constitutes a clinically meaningful objective change (3). We would add that this limitation extends to patient-reported outcomes: although the PD Questionnaire has been formally validated across the domains of psychological and physical symptoms, penile pain, and symptom bother (4), it is still inconsistently reported alongside objective deformity measures, which further constrains cross-study synthesis.

The four-domain framework proposed by the commentators, encompassing objective deformity, functional capacity, patient-reported outcomes, and treatment burden, is in our view of considerable clinical and methodological value, and we endorse it. PD management is progressively moving toward precision and individualization, and contemporary guidance reflects this direction. The Fifth International Consultation on Sexual Medicine explicitly frames management as an individualized process that balances the benefits and risks of each option against the needs and preferences of the individual patient (5), and the 2025 European Association of Urology guidelines similarly emphasize personalized, phase-aware decision-making (6). Future strategies should therefore be formulated not only on disease phase and plaque characteristics, but also on the degree of functional impairment, the psychological burden, and the therapeutic goals of each patient. What the field still lacks, and what we would highlight as a priority, is a consensus-derived core outcome set specifying which measures within each of these domains should be reported as a minimum in every PD intervention study.

We particularly endorse the commentators’ discussion of adherence to penile traction therapy (PTT). Accumulating evidence supports the capacity of PTT to preserve penile length and improve curvature; the largest randomized controlled trial to date demonstrated meaningful gains with a device requiring only 30 to 90 minutes of daily wear, a substantially lower burden than earlier-generation devices (7). Nevertheless, expert position statements have repeatedly noted that the overall evidence base remains limited and that protocol heterogeneity, in device type, daily wear time, and treatment duration, precludes strong recommendations (8). We therefore agree that objective adherence monitoring and adherence-adjusted analyses are needed. We would, however, add one methodological caveat: adherence is not randomly distributed. It is plausibly associated with symptom bother, motivation, partner support, and occupational circumstances, each of which may independently influence outcome. Per-protocol or adherence-stratified analyses will accordingly require prespecified handling of this confounding, ideally reported alongside intention-to-treat estimates, if they are to inform practice rather than overstate efficacy.

We fully concur that nonsurgical treatment should be understood as an integral component of the overall PD care pathway rather than an alternative or opposing option to surgery. Clinical pathways integrating the recommendations of the major societies have already advanced this staged model (9), and the commentators’ proposal of an explicit “decision checkpoint”, at which the minimum acceptable outcome, the maximum acceptable treatment burden, and the criteria for surgical transition are defined before prolonged conservative therapy begins, is a practical and welcome refinement. This is closely linked to their treatment-burden domain: formal cost-effectiveness analysis has shown that the relative value of surgery, collagenase Clostridium histolyticum, and PTT is highly sensitive to treatment cost and completion, such that the optimal strategy may differ substantially across health systems (10). Determining the optimal timing of transition from conservative management to surgery, stratified by deformity phenotype, severity of functional impairment, and patient expectation, therefore remains a key research priority.

Finally, we agree that novel therapeutic modalities for PD must be developed on the basis of rigorous study design, with unified disease definitions, standardized efficacy evaluation, and follow-up extending beyond early symptomatic change (3). Given the relatively low incidence of PD and the marked heterogeneity of deformity phenotypes, we would emphasize that multicenter collaboration and standardized prospective registries are likely prerequisites for generating adequately powered, phenotype-stratified evidence (1). We thank the commentators once again for their attention to our work and for their insightful suggestions, which we believe will further promote the standardized, patient-centered development of research on nonsurgical treatment for PD.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Andrology and Urology. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0688/coif). The authors have no conflicts of interest to declare.

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