BACKGROUND: Collagenase Clostridium histolyticum (CCH) remains the only Food and Drug Administration-approved medical treatment for Peyronie\'s disease (PD). The initial IMPRESS I and II trials (Investigation for Maximal Peyronie\'s Reduction Efficacy and Safety), which led to Food and Drug Administration approval, revealed a rate of treatment-related adverse events as high as 84%. Studies fail to provide clear definitions of complications.
OBJECTIVE: To review complications, provide a CCH complication atlas, and propose management strategies for commonly encountered complications.
METHODS: We performed a literature review using PubMed. A photographic atlas was provided regarding complications in patients in a high-volume CCH center for PD.
RESULTS: Complications were identified and classified by nature and severity. We followed a standardized previously published grading system for hematomas. Complications include bruising, swelling, hematoma formation, back pain, and, rarely, corporal rupture. Complications were discussed, and hematomas were graded by penile surface area. Complication photographs were graded and displayed. Treatment-related adverse effects do not affect overall results.
CONCLUSIONS: Recognizing and grading complications associated with CCH therapy for PD is crucial for effective patient management and informed decision making. A standardized grading system allows for consistency in reporting and comparing hematoma complication rates across studies and patient populations. Herein we provide images that will help clinicians identify and confidently manage common complications that may occur in any CCH program.

Male urethral stricture disease is highly prevalent and difficult to treat due to potential complications. Minimally invasive treatments tend to have high recurrence rates, keeping urethroplasty as the gold standard. Collagenase Clostridium histolyticum (CCH) has been used in humans to treat fibrosis in a minimally invasive manner. Herein, we present the preliminary results from treatments of three males with urethral stricture as a feasibility and safety evaluation of the first-in-human CCH treatment for male urethral stricture disease.

BACKGROUND: It is currently unclear if men with Peyronie\'s Disease (PD) who achieve minimal benefits with the first 2 series of Collagenase Clostridium Histolyticum (CCH) injections should continue with additional injections.
OBJECTIVE: To analyze curvature improvements from the final two series of CCH injections based on amount of improvement during the first 2 series.
METHODS: A prospective registry was analyzed of all men undergoing CCH injections for PD at a single institution. Men were included if they had completed a full 4 series (8 injections) of CCH and had baseline, interval (after 2 series), and/or final (after 4 series) curvature assessments available. Men were stratified into cohorts using baseline-to-interval assessments of ≤10° (or ≤20%) and >10° (or >20%), and improvements were compared using interval-to-final assessments.
RESULTS: The primary outcome was interval-to-final curvature improvements stratified by ≤10°/>10° or ≤20%/>20% improvements achieved during the baseline-to-interval period. Secondary outcomes included analyses of demographic and pathophysiologic variables to determine associations with significant improvements during the final 2 CCH series.
RESULTS: A total of 296 PD men were identified as receiving at least one CCH injection, of whom 175 had baseline-to-interval, 84 interval-to-final, and 115 with baseline-to-final measurements. Mean age was 56.6, PD duration 28.6 months, baseline curvature 63.4°, hourglass deformity 36.2%, and calcification 20%. Mean overall curve improvement was -21.5° (33.1%). Among men who experienced ≤20% improvements after 2 series, the mean subsequent curvature change was -24.6% during the final two series (vs +4.3% of those with >20% initial improvement, P< .001), and they were 2.7x more likely to experience >20% subsequent curve improvements. Thirty-one percent of those who achieved >10° during the first 2 series experienced benefits during the final 2 series compared to 70% of men who had ≤10° improvement initially. No demographic or pathophysiological variables predicted likelihood for improvements during the final 2 series of injections.
CONCLUSIONS: Men who fail to achieve significant benefits with 2 series of CCH injections may benefit from completing the final 2 series.
UNASSIGNED: Strengths including a relatively large, prospective series. Limitations include a single center, nonrandomization, nonblinded assessments, and restriction to men who completed eight injections.
CONCLUSIONS: In the current series, approximately 2/3 of men who fail to achieve >10° or 20% curve improvements with an initial 2 series of CCH injections achieved >10° or 20% improvements with the subsequent 2 series.

BACKGROUND: Intralesional collagenase such as Xiaflex (ILX) has become a standard treatment for Peyronie\'s disease (PD). Many robust studies have demonstrated its clear efficacy in the treatment algorithm.
OBJECTIVE: To examine predictors of the patient decision to pursue ILX in PD patients.
METHODS: The study included PD patients (i) with stable disease (ii) who had doppler duplex ultrasonography (DUS) at least 6 months prior to analysis date and (iii) did not choose an operation. All patients received a standard discussion regarding treatment options, specifically, observation, ILX and penile reconstructive surgery (plication, plaque incision and grafting, implant surgery). Patients who opted to use ILX were compared to those who opted against it. Comorbidity, demographic and PD characteristics were recorded at the initial PD visit. All patients completed three validated questionnaires including the PD questionnaire (PDQ), Self-Esteem and Relationship (SEAR) questionnaire and a depression questionnaire (CES-D). Logistic regression was used to determine predictors of ILX use.
RESULTS: Predictors of ILX utilization.
RESULTS: Four hundred and fifty stable PD men had DUS completed 6 months before to allow sufficient time for treatment decision. Of these, 111 (24.7%) patients had ILX treatment and 339 (75.3%) did not. Mean age, relationship status and pain occurrence were similar between groups, but ILX patients had less bother defined as PDQ ≥ 9 (46.8% vs 53.7%, P = .02). ILX patients had more complex curves (79.3% vs 47.8%, P < .01) and more severe instability (32.4% vs 15.3%, P = .01). ILX patients also had higher PDQ domain scores (Psychological 11.5 ± 6.4 vs 7.5 ± 6.2, P < .01; Pain 6.2 ± 6.0 vs 4.3 ± 5.6, P = .02; and Bother 9.8 ± 4.7 vs 6.6 ± 4.8, P < .01). On univariable statistics, significant bother (OR 2.41, 95% CI 1.36-4.28, P<0.01), complex curvature (OR 4.18, 95%CI 2.52-6.93, P < .01), moderate and/or severe instability (OR 1.98, 95%CI 1.18-3.30, P < .01) and PDQ-Bother scores (OR 1.15, 95%CI 1.08-1.22 P < .01) predicted ILX use. On multivariable analysis, instability (OR 2.58, 95%CI 1.02-6.57, P = .05) and significant bother (OR 1.23, 95%CI 1.04-1.45, P = .01) predicted ILX use.
CONCLUSIONS: Educates providers as to which patients are more likely to choose ILX.
UNASSIGNED: Our study has a large sample size and all patients received the same standardized treatment discussion. Our study is limited by the absence of insurance data on all patients, and its retrospective single center design.
CONCLUSIONS: ILX was chosen by the minority of stable PD patients. While moderate to severe instability and significant bother is predictive of ILX use, other demographic factors including relationship status, sexual orientation or pain were not.

Penile curvature is the most common abnormality that is observed by men with Peyronie\'s disease (PD). Collagenase Clostridium histolyticum (CCH) has become a standard treatment for PD patients.
To identify predictor factors associated with improvements of penile curvature outcomes in men with PD treated with CCH.
We retrospectively collected the data of patients with PD treated with CCH up to 8 injections divided into 4 cycles between January 2014 and July 2020. Per protocol, penile curvature was assessed at baseline, and after the second and ford CCH cycle. If after cycle 2, curvature demonstrated no improvement, or penile curvature was significantly improved and the patient was happy, no further treatment was recommended. However, if penile curvature was significantly improved and the patient remained dissatisfied, 4 cycles were completed. Three categories of response were evaluated: improvement (≥10 degrees or ≥20%, either 1 happens), unchanged (±10 degrees or ±20%) or worsened (≥10 degrees or ≥20%, either 1 happens). Logistic regression analyses were performed to evaluate predictive factors associated with penile curvature improvements.
Degrees of the curvature changes between the baseline and after the cycles of CCH.
A total of 114 patients underwent CCH treatment. Median age was 57 years. Median PD duration was 11 months. At baseline, mean curvature was 47 degrees, 65% had dorsal curvature, 53% mid-shaft location, and 15% calcification. After CCH treatment, the mean final curvature was 40 degrees. A total of 44% improved the curvature, 39% had no change while 17% worsened after CCH treatment. Of men who had penile curvature improvement with CCH treatment, the mean curvature decreasing in degrees and percentage were 22 degrees and 41%, respectively. Men with baseline curvature ≤ 30, 31-59, and ≥ 60 degrees, the percentage curvature improvement were 29%, 43%, and 60%, respectively. Baseline curvature was the only significant predictor of penile curvature improvement after CCH (OR 1.33, 95% CI = 1.1, 1.7).
We confirmed baseline penile curvature is the most important predictive factor, and this is the first report describing proportions of penile curvature improvement with CCH treatment.
This study has several strengths, including the use of validated instruments. Nonetheless, there are limitations: the retrospective nature of the study, a single institution; and modelling device was not controlled.
Penile curvature improvement was significantly more common in patients with greater baseline curvature, reaching up to 60% for patients with ≥ 60 degrees.

The clinical landscape of Peyronie\'s disease is everchanging. There has been growing interest in non-invasive therapeutic options that could assist patients with achieving a meaningful reduction in penile curvature without surgical intervention. These therapies are wide-ranging in terms of their mechanisms of action, efficacies, and short- and long-term safety profiles. Recently, an abundance of outcomes literature on longstanding and novel non-surgical treatment modalities has been published. For sexual medicine providers hoping to offer patients the most up-to-date and evidence-based treatments for the management of Peyronie\'s disease, it can be challenging to gain a thorough understanding of this body of literature. In this clinical management review, the workup and current theories on the pathophysiology of Peyronie\'s disease are reviewed, and the most recent outcomes data on the currently available non-surgical treatment modalities are presented. With an accurate understanding of the current landscape of Peyronie\'s disease treatment, sexual health providers will be able to better evaluate and engage in evidence-based shared decision-making with their patients.

UNASSIGNED: Based, in part, on the clinical study reports of tendon rupture events after collagenase clostridium histolyticum (CCH) (Xiaflex, Endo Pharmaceuticals Inc) treatment for Dupuytren contracture (DC), a Risk Evaluation and Mitigation Strategy program was instituted in 2010 by Auxilium Pharmaceuticals (now Endo Pharmaceuticals Inc) to ensure that the benefits of CCH injection outweighed the risks when treating DC. Using the postmarketing surveillance data collected in this program, a retrospective analysis was conducted to evaluate the incidence of flexor tendon rupture after CCH treatment for DC in the clinical practice setting.
UNASSIGNED: The Endo Pharmaceuticals Inc safety database was searched for cases of tendon rupture reported between February 2, 2010, and October 8, 2015. Total number of CCH treatments for DC and incidence of tendon rupture were estimated using CCH dosing derived from clinical trial experience (1.7 CCH vials/treatment) or clinical practice evidence (1.08 CCH vials/treatment).
UNASSIGNED: Over the 5.8-year surveillance period, 97,609 vials of CCH were distributed for the treatment of DC, equivalent to an estimated total of 57,416 treatments (at 1.7 CCH vials/treatment) or 90,378 treatments (at 1.08 CCH vials/treatment). Although CCH distribution increased during the surveillance period, reports of tendon rupture were infrequent (approximately 13 cases/y; total cases: flexor tendon, n = 57; ligament/pulley, n = 2), corresponding to a 0.10% (1.7 CCH vials/treatment) or 0.06% (1.08 CCH vials/treatment) mean estimated incidence of tendon rupture in patients with DC after CCH treatment.
UNASSIGNED: This retrospective analysis showed that flexor tendon rupture occurred infrequently in patients with DC who were treated with CCH in real-world practice settings between 2010 and 2015. On the basis of these findings and other favorable safety evidence, the Risk Evaluation and Mitigation Strategy program requirement for CCH for the treatment of DC was ended by the US Food and Drug Administration in November 2016.
UNASSIGNED: Therapeutic IV.

Peyronie\'s disease (PD) is a fibrotic condition of the penis characterized by abnormal plaque formation. Intralesional collagenase Clostridium histolyticum (CCh) is effective in noncalcified PD; however, its effectiveness in calcified PD is not well characterized.
To assess curvature improvement in calcified PD plaques treated with CCh.
We prospectively evaluated men with calcified PD electing CCh treatment at our institution from October 2018 to November 2020. We assessed curvature with artificial erection and goniometer before and at least 3 mo after treatment. We classified the type of plaque calcification based on ultrasound.
Intralesional CCh. Each treatment cycle consisted of two CCh injections (0.58 mg) into the plaque at the point of maximal penile curvature. The second injection was performed 72 h to 1 wk later, after which participants began modeling. All men were intended to receive a total of eight injections in four cycles, each 6 wk apart.
Change in penile curvature after CCh was measured. We assessed for differences in outcomes based on the number of injections and type of calcification. Unless otherwise specified, data are presented as medians (interquartile range).
Sixty men with calcified PD elected CCh; 47 had complete follow-up data. Thirty-nine men completed treatments with eight injections, while the remaining discontinued after a median of five (four to six) injections. There was no difference in response between type 2 and type 3 plaques. Curvature significantly improved by 17.5° (37.5-10.0°) in patients who completed treatment and by 15.0° (20.0-0.0°) in those who discontinued. Limitations include a small sample.
Men with calcified PD plaques improve with CCh treatment and show similar improvements regardless of calcification type.
In this study, we evaluated the efficacy of collagenase Clostridium histolyticum (CCh) treatment in calcified Peyronie\'s disease (PD) plaques. We found that treatment in calcified plaques demonstrated significant improvement in curvature and the grading of calcification did not impact the degree of curvature improvement. We conclude that participants with calcified PD plaques can benefit from nonsurgical CCh treatment.

Introduction  The aim of this study was to assess the rate of additional treatment after collagenase injection and needle fasciotomy, and what factors are associated with additional procedures for recurrence. Materials and Methods  We retrospectively identified 201 adult patients who underwent collagenase injection and 19 patients who underwent needle fasciotomy for Dupuytren\'s disease from 2012 to 2014. Outcomes included additional treatment of the same ray for either recurrence or persistence of contracture. To evaluate associated factors, we performed a bivariate analysis. Results  Additional treatment after collagenase injection for recurrence was performed in 24% of fingers at a median of 23 months (interquartile range [IQR]: 10.8-36.1) and was associated with bilateral disease ( p = 0.008). Additional treatment for persistence was performed in 5.6% at a median of 1.9 months (IQR: 1.1-3.2). Additional treatment for recurrence after needle fasciotomy was performed in 13% of fingers at a median of 28.2 months (IQR: 27.5-28.2) and 4.2% for persistence at 1.1 months. Fingers treated with needle fasciotomy were more likely to undergo secondary open fasciectomy (13% vs. 5.1%, p = 0.022). Conclusion  Additional treatment after collagenase injections was performed in 29% of fingers, mostly another collagenase injection, and was associated with bilateral disease. After needle fasciotomy, 17% of patients underwent additional treatment, primarily open partial fasciectomy.

Penile curvature is the most common abnormality that is observed by men with Peyronie\'s disease (PD). Collagenase Clostridium histolyticum (CCH) has become a standard treatment for PD patients.
To identify predictor factors associated with improvements of penile curvature outcomes in men with PD treated with CCH.
We retrospectively collected the data of patients with PD treated with CCH up to 8 injections divided into 4 cycles between January 2014 and July 2020. Per protocol, penile curvature was assessed at baseline, and after the second and ford CCH cycle. If after cycle 2, curvature demonstrated no improvement, or penile curvature was significantly improved and the patient was happy, no further treatment was recommended. However, if penile curvature was significantly improved and the patient remained dissatisfied, 4 cycles were completed. Three categories of response were evaluated: improvement (≥10 degrees or ≥20%, either 1 happens), unchanged (±10 degrees or ±20%) or worsened (≥10 degrees or ≥20%, either 1 happens). Logistic regression analyses were performed to evaluate predictive factors associated with penile curvature improvements.
Degrees of the curvature changes between the baseline and after the cycles of CCH.
A total of 114 patients underwent CCH treatment. Median age was 57 years. Median PD duration was 11 months. At baseline, mean curvature was 47 degrees, 65% had dorsal curvature, 53% mid-shaft location, and 15% calcification. After CCH treatment, the mean final curvature was 40 degrees. A total of 44% improved the curvature, 39% had no change while 17% worsened after CCH treatment. Of men who had penile curvature improvement with CCH treatment, the mean curvature decreasing in degrees and percentage were 22 degrees and 41%, respectively. Men with baseline curvature ≤ 30, 31-59, and ≥ 60 degrees, the percentage curvature improvement were 29%, 43%, and 60%, respectively. Baseline curvature was the only significant predictor of penile curvature improvement after CCH (OR 1.33, 95% CI = 1.1, 1.7).
We confirmed baseline penile curvature is the most important predictive factor, and this is the first report describing proportions of penile curvature improvement with CCH treatment.
This study has several strengths, including the use of validated instruments. Nonetheless, there are limitations: the retrospective nature of the study, a single institution; and modelling device was not controlled.
Penile curvature improvement was significantly more common in patients with greater baseline curvature, reaching up to 60% for patients with ≥ 60 degrees. Flores JM, Nascimento B, Punjani N, et al. Predictors of Curvature Improvement in Men With Peyronie\'s Disease Treated With Intralesional Collagenase Clostridium Histolyticum. J Sex Med 2022;19:1680-1686.