Intralesional Collagenase Clostridium Histolyticum for Acute Phase Peyronie's Disease

A Single-Center, Retrospective Cohort Study

Ming-Yeah Y. Hu; John T. Sigalos; Dyvon T. Walker; Michelle K. Li; Dar A. Yoffe; Neilufar Modiri; Thomas W. Gaither; Alvaro J. Santamaria; Keith V. Regets; Sriram V. Eleswarapu; Jesse N. Mills


Transl Androl Urol. 2022;11(8):1074-1082. 

In This Article

Abstract and Introduction


Background: Peyronie's disease (PD) can be subdivided into acute and chronic phases. Intralesional collagenase Clostridium histolyticum has been shown to improve curvature in the chronic phase. Initial clinical trials excluded patients in the acute phase from treatment. Recent studies show comparable results among men in the acute phase. The definition of acute phase varies among existing studies, but it is generally understood to last 12–18 months and is accompanied by penile pain and progression of deformity. We sought to evaluate the safety and efficacy of intralesional collagenase injection therapy during the acute phase of PD using multiple definitions of the acute phase.

Methods: All men receiving intralesional collagenase for PD from October 2015 through December 2020 at a single academic institution were retrospectively assessed for patient demographics and comorbidities, pre- and post-treatment curvature, and adverse events. Two definitions of acute phase were used: (I) acute phase duration ≤6 months, chronic phase duration >6 months; and (II) acute phase duration ≤12 months with penile pain, chronic phase duration >12 or no penile pain.

Results: Of 330 patients identified, 229 underwent intralesional collagenase treatment with pre- and post-treatment erect penile goniometry. 65 (28%) met criteria for definition 1 of acute phase, 37 (16%) met criteria for definition 2, and 76 (33%) met criteria for either. Percent change in penile curvature was not significantly different between acute and chronic phases using definition 1 (16.0% vs. 16.6%, P=0.89), definition 2 (19.9% vs. 15.7%, P=0.43), or either (16.5% vs. 16.3%, P=0.96). The rates of development of bruising, swelling, hematoma, or corporal rupture were not significantly different between the acute and chronic phases under either definition (all P>0.05).

Conclusions: This single-center, retrospective cohort analysis suggests that intralesional collagenase is both safe and effective for the treatment of men with acute phase PD. Limitations exist inherent to retrospective review, since many men did not return for post-treatment goniometry, possibly skewing our cohort toward incomplete responders. Prospective, randomized studies will be required to confirm these findings.


Peyronie's disease (PD) is a penile condition characterized by fibrotic plaque formation within the tunica albuginea, causing pain and deformity. It affects an estimated 3.2–12% of men in the United States, and up to 20.3% of men with metabolic comorbidities.[1–3] PD presents with concomitant erectile dysfunction (ED) in 40–50% of men. The physical manifestations of PD contribute to the development of emotional distress and relationship problems.[4–12]

The natural history of PD can be divided into the acute (active) phase and the chronic (stable) phase. The acute phase is typified by progressive changes in penile morphology and the presence of erectile pain. The chronic phase is generally defined by stability in penile morphology for at least three months, as well as absence of erectile discomfort.[13,14] The duration of the acute phase varies in the literature, although it is commonly accepted to last up to 12–18 months.[15–18] Surgical treatment for PD is most definitive but is reserved for those with stable disease. For patients with acute phase PD, some non-surgical and minimally invasive treatment options include L-citrulline, pentoxifylline, vitamin E, and intralesional interferon-α2b, verapamil, or hyaluronic acid.[15,18–23]

Intralesional injectable collagenase Clostridium histolyticum (trade name Xiaflex, Endo, Malvern, PA) works by cleaving the irregular amalgamations of collagen in PD plaques and is the only United States Food and Drug Administration (FDA) approved treatment for PD.[24] The IMPRESS (Investigation of Maximal Peyronie's Reduction and Safety Studies) trials showed that intralesional collagenase with penile modeling significantly reduced curvature 32.4% and 34% with an acceptable safety profile.[25,26] Those studies excluded patients in the acute phase of PD. Small studies have examined intralesional collagenase use in the acute phase.[27–29] Nguyen et al. was the first to explicitly compare the acute and chronic phases in a single- and recently multi-institutional study, demonstrating no difference in efficacy and safety profile of collagenase between groups using a 12-month (with pain) cut-off and a 6-month cut-off respectively.[30,31] However, more research in collagenase for acute phase PD is needed. Our study aims to retrospectively evaluate our institutional use of collagenase for acute phase patients as defined by those two definitions and to determine whether treatment with intralesional collagenase in the acute phase in our large patient cohort is safe and effective. We present the following article in accordance with the STROBE reporting checklist (available at