Phenotype-directed endpoints for nonsurgical Peyronie’s disease management

We read with great interest the recent editorial by Kam, Shin, and Chung, “Current status of non-surgical treatments for Peyronie’s disease” (1). The authors provide a timely and clinically useful synthesis of contemporary nonsurgical options, including collagenase Clostridium histolyticum (CCH), selected intralesional alternatives, penile traction therapy (PTT), vacuum erection devices, extracorporeal shockwave therapy, and the limited role of oral or topical monotherapy. We particularly appreciate the authors’ balanced view that nonsurgical care should be phase-aware, preference-sensitive, and realistic in its expected goals.

Building on this discussion, we believe that the next step in nonsurgical Peyronie’s disease (PD) management should move beyond treatment-centered summaries toward phenotype-directed endpoints. In daily andrology practice, “success” after nonsurgical treatment extends beyond numerical curvature reduction alone, a limitation also reflected in the heterogeneity of endpoints across contemporary nonsurgical PD literature (2-4). A patient with residual curvature below a conventional threshold can still experience sexual difficulty if indentation, hinge effect, shortening, erectile dysfunction, or partner-related limitations persist. Conversely, a modest objective change in curvature can be clinically meaningful if it restores penetrative intercourse, reduces bother, or prevents further perceived length loss.

We therefore propose that future studies and clinical counseling separate at least four outcome domains. First, objective deformity should include not only curvature degree, but also curvature direction, multiplanar deformity, indentation or hourglass narrowing, axial instability, plaque calcification, and stretched or erect penile length. Second, functional outcomes should capture penetrative capacity, erectile rigidity, need for pharmacologic erectile support, and the ability to complete intercourse without unacceptable discomfort. Third, patient-reported outcomes should include validated measures of bother, sexual confidence, treatment satisfaction, and expectation fulfillment. Fourth, treatment burden should be recorded, including number of visits, out-of-pocket cost, device wear time, adverse events, discontinuation, and subsequent surgical conversion.

This framework is particularly important for PTT. As the editorial correctly notes, traction is most useful when adherence is high and can provide length preservation or additional curvature improvement when combined with CCH (5,6). However, adherence itself is a major determinant of real-world effectiveness. Device comfort, daily wear time, concealability, partner support, and occupational constraints often determine whether a biologically plausible intervention becomes clinically effective. Future PTT trials should incorporate digital or diary-based adherence tracking, prespecified minimum effective wear-time categories, and separate reporting of curvature and length outcomes. Without adherence-adjusted analyses, negative or modest findings may reflect implementation failure rather than lack of biological efficacy.

Another clinically relevant issue is the interface between nonsurgical and surgical pathways. The editorial appropriately highlights functional straightness, pain control, length preservation, and sexual function as practical goals (1). We propose that clinicians define a “decision checkpoint” before initiating prolonged or costly nonsurgical therapy. This checkpoint should include the patient’s minimum acceptable outcome, maximum acceptable treatment burden, and criteria for transition to surgery. Men with stable complex deformity, significant hinge effect, severe shortening, or medication-refractory erectile dysfunction should receive timely surgical counseling rather than automatically proceeding through repeated conservative treatment cycles (7). In this sense, nonsurgical therapy should not be framed as the opposite of surgery, but as part of a staged reconstructive pathway.

CCH remains the best-supported nonsurgical deformity-directed option for selected patients with eligible stable-phase PD (1,5). Nevertheless, real-world implementation is strongly influenced by access, cost, and regional availability. This is especially relevant in settings where CCH is unavailable or difficult to afford. In such contexts, clinicians frequently rely on PTT, selected intralesional alternatives, pain-directed therapy, and counseling; however, these strategies should be presented with transparent expectations rather than as equivalent substitutes. Comparative effectiveness studies should therefore report not only efficacy under trial conditions, but also completion rates, adherence, costs, retreatment, and eventual surgical conversion (8,9).

We also support the authors’ caution regarding oral, topical, platelet-rich plasma, and other investigational approaches (1). In a disease characterized by fluctuating pain, variable natural history, and strong placebo effects, uncontrolled improvement can be easily overinterpreted. For emerging therapies, trial design should prioritize standardized photography or three-dimensional assessment, stable definitions of disease phase, validated patient-reported outcomes, and follow-up beyond early symptom changes.

In conclusion, Kam and colleagues have provided a concise and valuable overview of nonsurgical PD treatment. Building on their work, we argue that the field should move from treatment-centered evaluation toward phenotype-directed, goal-based endpoints. Such an approach can better align trial design, physician counseling, and patient expectations, while clarifying when conservative management is reasonable and when definitive reconstruction should be discussed.

Acknowledgments

AI Assistance Disclosure: AI-assisted tools were used for language editing. All scientific content, interpretation, and conclusions are the sole responsibility of the authors.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. 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-2026-0552/coif). The authors have no conflicts of interest to declare.

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References

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