Beyond penile pain: is it time to reconsider phase-based treatment strategies in Peyronie’s disease?

Peyronie’s disease (PD) has traditionally been divided into active (acute) and stable (chronic) phases, a classification that has served as the basis for therapeutic decision-making for decades (1). This framework has been particularly useful in surgical planning, where correction of penile deformity has generally been recommended only after disease stabilization. Consequently, penile pain and symptom duration have often been regarded as surrogate markers of disease activity, frequently leading clinicians to postpone intervention until the presumed stable phase. However, whether this traditional paradigm deserves careful reconsideration in the era of expanding therapeutic options.

In this issue of Translational Andrology and Urology, Mills and colleagues analyzed pooled data from the landmark IMPRESS I and II trials and demonstrated that baseline penile pain did not influence the efficacy of collagenase Clostridium histolyticum (CCH) (2). Men with and without penile pain experienced comparable improvements in penile curvature, and among patients reporting pain, treatment outcomes were similar irrespective of how long the disease had persisted beyond 12 months. These findings provide additional evidence that penile pain should not be considered a contraindication to collagenase therapy or a determinant of expected treatment response.

More importantly, this study raises a broader question that extends beyond collagenase therapy itself. Should treatment selection in PD continue to depend primarily on the traditional distinction between active and stable disease?

The historical classification of PD was established largely during an era when surgical reconstruction represented the principal therapeutic option. Because penile deformity could continue to progress during the active inflammatory phase, postponing surgery until curvature stabilized was both rational and clinically appropriate. However, modern treatment strategies have expanded considerably and now include intralesional collagenase, penile traction therapy, vacuum erection devices, pharmacological therapy, and combinations of these approaches. Each treatment has a different mechanism of action and therapeutic objective. Consequently, applying the same phase-based treatment restrictions to every modality may no longer be scientifically justified.

This concept is particularly relevant for collagenase therapy. Unlike reconstructive surgery, CCH acts directly on collagen within the Peyronie’s plaque. From a biological perspective, intervention before extensive collagen maturation and irreversible fibrosis develop may theoretically interrupt plaque remodeling rather than simply reduce an already established deformity. Although this hypothesis requires prospective validation, the present study suggests that persistent penile pain alone should not delay treatment. The inclusion criteria of the original IMPRESS trials should therefore not automatically be interpreted as defining the optimal timing of therapy in routine clinical practice (3).

A similar consideration applies to conservative medical therapy. Current guidelines generally do not recommend routine oral pharmacotherapy because of limited high-quality evidence (1). However, many earlier clinical trials enrolled heterogeneous patient populations, used inconsistent definitions of active disease, and included broad variations in symptom duration. Consequently, the true efficacy of medical therapy during the earliest inflammatory stage remains uncertain. It is possible that carefully selected patients with biologically active disease may respond differently from those enrolled in previous studies. Future clinical trials should therefore emphasize accurate characterization of disease activity rather than relying solely on arbitrary temporal definitions.

Accordingly, the present study should not be interpreted simply as evidence supporting the safety and efficacy of collagenase in men with penile pain. Rather, it encourages reconsideration of the broader framework by which treatment timing is determined. Disease activity in PD is unlikely to be adequately represented by a single symptom such as penile pain (4). Instead, treatment decisions should integrate multiple clinical variables, including deformity progression, plaque characteristics, erectile function, symptom burden, patient expectations, and treatment-specific mechanisms of action.

The historical classification of PD into active and stable phases remains clinically useful for describing disease evolution, but it should no longer serve as the primary determinant of treatment eligibility. As therapeutic options continue to expand, treatment selection should increasingly be guided by the mechanism of each intervention and the patient’s individual disease phenotype rather than by phase classification alone (5).

The study by Mills and colleagues represents another important step toward this evolving paradigm. Rather than asking whether a patient has entered the stable phase, future research should focus on identifying which patients are most likely to benefit from specific therapies at different stages of disease evolution. Such a personalized strategy has the potential not only to optimize treatment outcomes but also to shift the management of PD from correction of established deformity toward earlier modification of disease progression.

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: The author has completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0731/coif). The author has no conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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