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Collagenase clostridium histolyticum for the treatment of Peyronie's disease: A prospective Italian multicentric study
Abstract
Peyronie's disease (PD) is a common condition which results in penile curvature making sexual intercourse difficult or impossible. Collagenase clostridium histolyticum (CCH) is the first licensed drug for the treatment of PD and is indicated in patients with palpable plaque and curvature deformity of at least 30° of curvature. However, only few monocentric studies are available in the current literature and this is the first national multicentric study focusing on this new treatment. In five Italian centres, 135 patients have completed the treatment with three injections of CCH using Ralph's shortened modified protocol. The protocol consisted of three intralesional injections of CCH (0.9 mg) given at 4‐weekly intervals in addiction to a combination of home modelling, stretching and a vacuum device on a daily basis. An improvement in the angle of curvature was recorded in 128/135 patients (94.8%) by a mean (range) of 19.1 (0–40)° or 42.9 (0–67)% from baseline (p < 0.001). There was also a statistically significant improvement in all IIEF and PDQ questionnaires subdomains (p < 0.001 in all subdomains). This prospective multicentric study confirms that the three‐injection protocol is effective enough to achieve a good result and to minimize the cost of the treatment.
... 8 Although subsequent study designs have varied, multiple studies have demonstrated an improvement in the degree of curvature ranging from 13° to 23°. 50,56 Most recently, a 2022 meta-analysis found an average improvement in curvature of approximately 19° more than that of placebo. 57 Besides these objective measures of improvement, CCH also has been demonstrated to consistently improve PDQ and IIEF scores. ...
... 57 Besides these objective measures of improvement, CCH also has been demonstrated to consistently improve PDQ and IIEF scores. 48,51,54,56 A pooled safety analysis of six studies done in 2015 found that 86% of CCH patients had at least one treatmentrelated side effect. 58 However, they were most often minor, including ecchymosis, swelling, mild hematoma, and pain. ...
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.
... The average IIEF-5 score before treatment was 18.1 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). This score increased to 20.2 (10-25) after treatment. ...
... This is the only treatment method licensed by the FDA. The effectiveness of Collagenase clostridium histolyticum has been proven by many recent studies [14][15][16]. However, especially in developing countries, using this agent can be very costly and the procurement of the drug can be difficult. ...
... In the IMPRESS trials, collagenase was directly injected into the primary plaque at the point of maximal penile curvature deformity with a standardized injection technique, with no mention of penile nerve block before the injection (Gelbard et al., 2013). However, in the following years, other authors in their works using CCH injections do specify the use of penile block prior to the treatment (Abdel Capece et al., 2018;Fernández-Pascual et al., 2019). ...
... They mentioned the use of a dorsal penile nerve block with lidocaine 1% prior to CCH injections. This same protocol was followed by Capece et al. (Capece et al., 2018), who published their results with 135 patients from five Italian centres, combining CCH injections with home penile modelling and the use of vacuum device. A penile block with 10 ml of lidocaine 1% was performed before each injection, to minimize the discomfort during the procedure also in this study. ...
The intraplaque injection of collagenase from Clostridium Histolyticum (CCH) was established as an effective therapeutic alternative for selected patients with Peyronie's disease (PD). There is no consensus on the use of pre‐procedure anaesthesia. The aim of this pilot study was to assess the efficacy and safety of dorsal penile block before CCH injections in reducing procedure related pain. The treatment protocol described in the IMPRESS trials was adopted. The first injection of the first cycle was given without anaesthesia, while the second after penile block. After the administration of each injection, the pain related to the procedure was evaluated with the Wong‐Baker‐FACES®‐Pain‐Rating‐Scale. Thirty patients were included. Mean age 56.7 (SD : 9.61) years. Mean basal penile curvature 59.37º (SD : 18.26). The mean pain value related to the procedure measured after the first injection of the first cycle (without anaesthesia) was 5.4 (SD : 2.13), while after the second injection (with anaesthesia) was 2.5 (SD : 1.92), (p < .001). The treatment was more painful in patients with dorsal plaques (mean:6.2) than in patients with lateral plaques (mean: 4.35) (p = .01). We can conclude that penile block before CCH injection in patients with PD seems an effective and safe measure to decrease the pain related to the procedure.
... Therefore, men with significant ED are generally excluded from trials evaluating CCH. The most widely utilized questionnaire for erectile dysfunction is the international index 15 and curvature in 135 patients who received treatment consisting of three intralesional injections of CCH on the high-dose "modified protocol". After the treatment, IIEF-15 score has increased by a mean of 5.32, IIEF-EF (erectile function) improved by 1.6, and curvature decreased by − 19.07° (15.0-20.0) ...
... intercourse satisfaction (9.9-11.4) and overall satisfaction (8.6-9.8) [15]. It is important to note that the baseline IIEF score in this study was 23.4, which is classified as no erectile dysfunction. ...
Purpose
To evaluate characteristics predictive of successful treatment outcomes of Peyronie’s disease (PD) with collagenase clostridium histolyticum (CCH)
Methods
CCH is the only FDA-approved medication for treating PD. We reviewed the literature that addresses pre-treatment clinical characteristics that may predict favorable response to CCH therapy.
Results
Despite significant heterogeneity in reporting treatment success, we identified four well-studied characteristics that may be predictive of favorable response to CCH therapy: baseline penile curvature, baseline IIEF, duration of PD, and presence of calcification. CCH demonstrated a favorable response in those with pre-treatment curvature 30°–60°, longer duration of disease, mild to moderate baseline sexual function, and low calcification within plaques. Of all factors, calcification is emerging as the most significant factor likely because CCH is unable to degrade the calcified plaques. There is difficulty interpreting results because of differences in reporting outcomes. Some studies compared treatment groups to placebo, others reported changes in curvature, while others reported > 20% curvature correction as treatment success. Additionally, not all studies reported outcomes after completion of four cycles of CCH, and recent studies utilized a shortened, high dose, modified protocol.
Conclusions
The ideal candidate for CCH therapy remains elusive. Based on the available literature, the man with PD who will have the greatest chance of curvature improvement will have curvature between 30° and 60°, longer duration of disease, an IIEF > 17, no calcification, and set to receive all four cycles. For a greater understanding of CCH treatment success in PD, prospectively collected registry reporting standardized outcomes are needed.
... The investigators assessed approximately 900 men, between the two studies, and reported an approximate 34.0% improvement in penile curvature when compared to the 18.2% improvement seen in the placebo group [33]. Subsequent investigations and reviews, some with variable dosing regimens when compared to the original IMPRESS cohorts, have been reported and demonstrated similar efficacy [32,34]. CCH is now recommended in the AUA guidelines in the treatment of PD, and the first licensed drug by the United States Food and Drug Administration (FDA) in the treatment of PD [1,34]. ...
... Subsequent investigations and reviews, some with variable dosing regimens when compared to the original IMPRESS cohorts, have been reported and demonstrated similar efficacy [32,34]. CCH is now recommended in the AUA guidelines in the treatment of PD, and the first licensed drug by the United States Food and Drug Administration (FDA) in the treatment of PD [1,34]. ...
Purpose of Review
To explore the potential hurdles surgeons may encounter when preforming surgical correction of penile curvature in patients with Peyronie’s Disease following intralesional collagenase clostridium histolyticum injections.
Recent Findings
Although limited data exists, retrospective analysis of surgeon experiences in surgical treatment of refractory penile curvature in patients with Peyronie’s disease appears to not result in more post-operative complications and may only slightly increase intra-operative difficulty.
Summary
As the use of intralesional collagenase clostridium histolyticum continues to increase and patients who demonstrate persistent curvature despite treatment seek further management, the role of investigating the feasibility of surgery demonstrates significant importance. Although limited data exists, it appears that surgery following intralesional collagenase clostridium histolyticum is safe without added post-operative complications. At the present time, however, further data on intra-operative findings and post-operative outcomes remain necessary, and as the use of this intralesional therapy continues to rise, further information should become readily available.
... 17 in the original studies of Gelbard et al. of eight injections in total and Abdel Raheem et al. of three injections combined with VED.10,12 In a large multicentre study of 135 patients, a reduction of curvature of 19.1 (p < 0.001) was established using the modified scheme in 94.8% of patients.24 El-Khatib et al. treated 21 men with stable PD with CCH. ...
Abstract Objective To describe the results of intralesional Collagenase Clostridium histolyticum (CCH) treatment in patients with Peyronie's disease (PD) in real‐world setting. PD is characterized by curvature of the erect penis caused by fibrotic tissue in the tunica albuginea. Patients and methods Patients with stable PD and curvature of 30° to 90° were prospectively enrolled. CCH injections were initially given using a scheme of four cycles of two injections within 48–72 h every 6 weeks. Later using a modified scheme of three injections every 4 weeks, combined with a vacuum erection device (VED) twice daily. All patients were requested to take pictures of the erect penis prior to and following treatment, from above and laterally. Curvature was measured by three independent researchers based on the provided pictures using a goniometer. Furthermore, patients filled in the Peyronie Disease Questionnaire‐NL (PDQ‐NL) and Patient Reported Outcome Measurement (PROM). The primary outcome was reduction in curvature and the ability to have penetrating sex again. Secondary outcomes include pain scores during injections, changes in PDQ‐NL, PROM and complications of CCH treatment. Results Sixty‐three patients were included, mean age was 56.0 years (range 39–70) and mean reduction in curvature 20.6° (SD 10.2, range 5–49); 74.5% of the patients were able to have penetrating sex again following treatment, compared with 41.2% prior to treatment. According to the PROM questions, sexual improvement was seen in 66.7% of patients. The satisfaction rate was 6.8 (SD 1.8). All patients save two recommend treatment. Conclusions Intralesional treatment with CCH in men with PD leads to a mean curvature improvement of 20.6°. Following treatment, 74.5% of men were able to have sexual intercourse and 54.9% of the couples were satisfied with their sex life. No major complications occurred in the patients treated with CCH. CCH is not available in Europe anymore despite good results.
... In contrast, a modified CCH regime using three CCH injections as compared to the IMPRESS treatment protocol with eight CCH injections was reported to be equally effective and safe [14]. The efficacy of this modified CCH schedule was confirmed in another study [15]. Despite the larger volume in the ILV in our study, i.e., 10 mg/4 mL of verapamil vs. 0.58 mg/0.5 mL CCH reconstituted injections, the CCH group showed greater improvement in the penile curvature compared to the ILV group (p<0.01) ...
Purpose:
To compare clinical outcomes and patient satisfaction rates between intralesional verapamil (ILV) and collagenase Clostridium histolyticum (CCH) injections in males with Peyronie's disease (PD).
Materials and methods:
Following ethics approval, PD patients were prospectively enrolled in this open-label non-blinded study. Patients were randomised to receive ILV or CCH injections with penile remodelling every fortnightly for 6 courses. Patient demographics, change in penile curvature, International Index of Erectile Function-15 and Peyronie's Disease Questionnaire (PDQ) scores as well as overall patient satisfaction and Patient Global Impression of Improvement (PGI-I) scores were recorded at pre-treatment and 6-, 12- and 24-month post-treatment.
Results:
A total of 50 males were recruited and divided into ILV (n=25) and CCH (n=25) groups. The mean changes in penile curvature were -16.8 (standard deviation [SD] 7.65) degrees in ILV and -28.2 (SD 11.5) degrees in CCH groups (p<0.01). Patients in the CCH group scored better than the ILV group on the PDQ psychosexual symptoms (-2.14 vs. -2.9; p<0.01) and symptom bother score (-3.88 vs. -4.16; p=0.08). Minor treatment-related adverse events were more common in the CCH group. The overall satisfaction rate on a 5-point scale was 4.1 in ILV and 4.5 in CCH groups, and there was no statistically significant difference in the PGI-I scores between the 2 groups (p=0.14).
Conclusions:
CCH therapy is more effective than ILV to treat a carefully selected group of males with PD, with a reasonable safety profile and a higher high level of patient satisfaction rate in the short term.
... Abdel Raheem et al. and Capece et al., in 2 prospective non-randomized studies with 53 and 135 patients, respectively, studied CCH treatment in a modified short protocol application (3 cycles of 0.9 mg each at 4-week intervals). They demonstrated a significant reduction in penile curvature, with lower costs and a shorter duration of treatment (31,32). ...
Introduction:
Peyronie's disease is the disease that results in an alteration in the curvature of the penis, which can lead to a shortening of length, pain in erection, or difficulties in penetration, thus leading the patient to psychological alterations due to loss of functionality such as aesthetic alteration. That is why there are several studies to define the best form of treatment, which currently continues to be the first choice surgical treatment.
Objective:
We present the most recommended therapies for Peyronie's disease and suggest an algorithm as a guide to direct therapy.
Methods:
We used the PubMed platform to review the literature related to Peyronie's disease. Various editorials were reviewed as well as original articles and reviews focusing on the various treatments as well as their indications and results.
Results:
Peyronie's disease in which conservative or drug treatment does not have a response, surgical treatment with corporoplasty, penile prosthesis implantation or both may be indicated. Corporoplasty refers to both the plication of the tunica albuginea as well as the incision of the tunica with the placement of a graft. An accurate history should always be carried out to identify erectile dysfunction as well as to be able to guide you on the repercussions of the treatment. If refractory erectile dysfunction is present, placement of a penile prosthesis with or without further adjunctive straightening maneuvers is recommended. We reviewed the indications, advantages, disadvantages, and results of the available techniques, and proposed a surgical treatment algorithm.
Conclusion:
Penile shortening procedures are usually indicated in curvatures <60°, in penises with adequate length. Partial excision/incision and grafting are indicated for curvatures >60°, hourglass or hinge deformities, and short penises, if the patient's erectile function is adequate. The presence of "borderline" erectile function and/or ventral curvature tilts the choice toward shortening procedures, and refractory erectile dysfunction is an indication for penile prosthesis placement. An accurate risk/benefit assessment of the individual patient as well as meticulous patient counseling are critically important.
... 21 A recent review summarizes 10 various retrospective and prospective series evaluating ILX since FDA approval which have demonstrated improvements ranging from 32-43% reinforcing the continued need to give prospective ILX patients realistic expectations. [22][23][24][25][26][27][28][29] To date, no study published since FDA approval has equaled the 75% improvement rate seen in the IMPRESS trials. ...
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.
Aim:
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.
Outcomes:
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.
Clinical implications:
Educates providers as to which patients are more likely to choose ILX.
Strengths & limitations:
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.
Conclusion:
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. Punjani N, Nascimento B, Salter C, et al. Predictors of Pursuing Intralesional Xiaflex in Peyronie's Disease Patients. J Sex Med 2021;XX:XXX-XXX.
... The effectiveness of intraplaque collagenase Clostridium histolyticum (CCH) in reducing penile curvature (PC) and improving sexual function in men with Peyronie's disease has been demonstrated in numerous clinical studies [1][2][3] , In this context, Cocci et al. 4 reported a significant efficacy in up to 57% of their cohort of patients, with baseline PC (odds ratio [OR] 1.14; p < 0.01), basal plaque (OR 64.27; p < 0.01), low calcification (OR 0.06; P < 0.01) and high calcification (OR 0.03; P < 0.01) emerging as predictors of PC improvement (≥ 20°). Notwithstanding this reported efficacy, long-term follow-up studies have been scantly published up to now 5 . A recent updated phase 4 study which included men who had received CCH during the IMPRESS I/II trials, reported that at 5-year assessment (n = 180), despite no additional treatment, there was a significant additional 9.1% improvement in terms of mean PC as compared with reference data 6 . ...
In the present study we aimed to investigate the surgical outcomes of patients with persistent penile curvature (PC) after Collagenase Clostridium histolyticum (CCH) intraplaque injections. Data from 90 patients with persistent PC after CCH in a multicentre study from 6 andrological centres were retrospectively reviewed. Three standardized surgical techniques were performed. Group 1: plaque incision grafting (PIG) with penile prosthesis implant (PPI); Group 2: PIG without PPI; Group 3: Nesbit technique. Hospital stay, operative time, postoperative complications and PC persistency/recurrence (> 20°) were evaluated. Overall satisfaction and functional outcomes were assessed through International Index of Erectile Function-Erectile Function (IIEF-EF), Peyronie’s Disease Questionnaire (PDQ), Female Sexual Function Index (FSFI) administered pre and 3 months postoperatively. Of all, 25 (27.8%) patients received grafting procedure + PPI (Group 1), 18 (20.0%) patients belonged to Group 2, and 47 (52.2%) to Group 3. Bovine pericardium graft and collagen fleece have been used in in 22 (51.2%) and 21 (48.8%) patients, respectively. Median penile length after surgery was 13.0 cm (IQR 12.0–15.0). After surgery, Group 1 showed higher increase in penile length after surgery and better improvements in terms of PDQ-PS. In contrast, both IIEF-EF and FSFI scores did not differ among groups. Overall, 86 (95.6%) did not report any complication. 4 (4.4%) patients had PC recurrence; of those, 2 (8.0%), 1 (5.6%) and 1 (2.1%) cases were observed in Group 1, Group 2 and Group 3, respectively. In case of persistent PC after CCH, surgical correction by grafting with or without concomitant PPI or Nesbit technique emerged as a technically feasible, effective and safe procedure, with no significant postoperative complications.
... In this light, PD is generally divided into two different phases: active or acute and stable or chronic. Plaque formation generally occurs during the acute phase [8,9]. Soon thereafter, during the chronic stage, penile pain will be reduced, and penile deformity stabilized. ...
Peyronie's disease (PD), a fibrotic disorder of the tunica albuginea fully described in 1793 by French physician Francois de la Peyronie, is characterized by pain, plaque formation, penile deformity, and ultimately sexual function decline. The epidemiological data on PD vary considerably across previous studies, with recent evidence reporting a prevalence of up to 9%. PD is generally divided into two different phases: active or acute and stable or chronic. Plaque formation generally occurs during the acute phase, while during chronic phase pain usually tends to complete resolution and penile deformity stabilizes. PD's pathophysiology is still subject of great discussion. Tunical mechanical stress and microvascular trauma are major contributory factors. However, better understanding of the molecular pathophysiology of this condition remains paramount towards an in-depth comprehension of the disorder and the development of newer and more effective disease-targeted interventions. In this review we provide a detailed overview of natural history of PD, specifically focusing on clinical manifestations and the underlying molecular regulation patterns.
... They concluded that this protocol was safe, effective, cost-efficient, and the results were comparable with the IMPRESS data [15,30]. This same scheme was followed by Capece et al. [31], who published their results with 135 patients from five Italian centers, obtaining an improvement in curvature in 94.8% of the patients, with an average reduction in curvature of 19°(−43%). ...
The aim of this paper is to analyze our experience with intraplaque administration of collagenase from Clostridium Histolyticum (CCH) together with penile modeling for selected patients with Peyronie’s disease (PD). We conducted a prospective, multicenter, single-arm study. Patients were included from October 2015 to August 2019. We carried out the I + E PROTOCOL (IMPRESS + extender). Each cycle involved administration of two injections of CCH separated 24–72 h, up to a maximum of four cycles. 24–48 h after injection patients underwent penile modeling maneuvers with the use of a PTD at home for at least 4 h a day. After each cycle, penile curvature was evaluated by the Kelami test. Mean pretreatment curvature was 57° (30–100). Eighty-seven patients underwent at least a single cycle and were eligible for analysis. Mean number of cycles administered was 2. Final average curvature after treatment, regardless of the number of cycles was 34°, with a mean reduction in curvature of −23.29° (−41%). Across the first three cycles we found statistically significant differences in the means in terms of the degrees of curvature after each cycle (p < 0.05), however this was not maintained in the fourth cycle. Statistical significance was also found when comparing the initial and final curvature after the complete treatment. We can conclude that treatment with CCH for PD is safe and effective. The concomitant use of CCH and PTT may limit the number of treatment cycles necessary to optimize outcomes when compared with CCH alone.
... (Cocci, Russo, Briganti, et al., 2018;Gelbard et al., 2013;Lipshultz et al., 2015). A standardised protocol of injections has not been established yet, considering that the modified shortened protocol (three injections) has given comparable results to the initial IMPRESS protocol (eight injections; Abdel Capece et al., 2018). However, there is a minority of patients who may not be completely satisfied after three injections and may want to receive a second cycle of three injections. ...
The purpose of this study was to evaluate the effectiveness and safety of the second cycle of Collagenase Clostridium histolyticum injections using the modified shortened protocol. We performed a retrospective analysis on patients who had already undergone the first cycle of injections using the modified shortened protocol and requested more injections to improve the remaining curvature. The International Index of Erectile Function, the Peyronie's Disease Questionnaire and the Global Assessment of Peyronie's Disease questionnaire were self‐administered to all patients. All the parameters were recorded at baseline, after the first cycle and after the second cycle of injections. All adverse events were recorded. Seventeen patients completed two cycles of injections. All patients had a reduction of the initial curvature after the first cycle, with a mean improvement of 17.4° (27.4%). After the second cycle, the reduction of the curvature was 7.9° (17.1%), and 29.4% of patients had no further improvement. No severe side effect was recorded. The results of the present study confirm the effectiveness and safety of the modified shortened protocol of Collagenase C. histolyticum injections for Peyronie's disease. However, the second cycle of three injections may be less effective, and patients may not be completely satisfied.
... Although surgery remains the gold standard treatment option for patients with stable PD, it is not recommended for men in the active phase. On the other hand, collagenase clostridium histolyticum (CCH) represents the only licensed drug for the minimally invasive treatment of PD [14,15], however the acute phase of PD is not currently an indication for CCH therapy [3,16,17]. Four studies [18][19][20][21] demonstrated significant improvements in penile curvature after 10 or 15 mg intralesional verapamil, although the protocols varied widely, ranging from 6 to 12 injections. ...
Purpose:
To compare the efficacy and safety of intralesional hyaluronic acid (HA) as compared with verapamil injection in patients with Peyronie's disease (PD).
Materials and methods:
Between January 2015 and December 2018, men in PD acute phase were prospectively recruited. This open-label, prospective study included 2 different protocols. Group A: 8-week cycle of weekly intraplaque injections with HA; Group B: 8-week cycle of weekly intraplaque injections with verapamil. Penile curvature, plaque size, International Index of Erectile Function (IIEF)-15 score and visual analogue scale (VAS) were assessed at baseline and after 3 months.
Results:
Two-hundred forty-four patients were enrolled. Of these, 125 received intralesional HA (Group A), 119 received intralesional verapamil (Group B). At enrollment, median age was 56.0 years (interquartile range [IQR]=47.0-63.0 years), median curvature 35.0° (IQR=25.0°-45.0°), median IIEF-15 score 19.0 (IQR=16.0-23.0), median VAS 4.0 (IQR=4.0-5.0). Median difference for IIEF-15 was 1.0 (95% confidence interval [CI]=1.12-1.94) in Group A and 0.0 (95% CI=-0.04-0.14) in Group B (p<0.05) and median difference for VAS score was -4.0 (95% CI=-4.11--3.65) in Group A and -1.0 (95% CI=-0.50-2.01) in Group B (p<0.05). Plaque size decreased by -1.50 mm (IQR=1.60-2.10 mm) in Group A and -1.20 in Group B (p=0.10), while penile curvature decreased by -9.50° (IQR=4.50°-13.00°) in group A and -4.50 (IQR=2.50-7.50) in Group B (p<0.01).
Conclusions:
Intralesional HA injections could represent a reliable treatment option for the conservative management of patients with acute phase of PD.
... It has been shown that initial injections in a treatment course result in greater benefit than later injections, suggesting that shortened protocols may be effective [8]. Higher doses of CCh across fewer injections have also been employed [7,9,10], as has the administration of the drug along three different needle tracks after a single insertion of the needle [7]. Taken together, the current literature has broadened the use of CCh by comparing efficacy using a standardized quantitative measurement: curvature. ...
Purpose
Early clinical trials of injectable collagenase Clostridium histolyticum (CCh) for Peyronie’s disease (PD) demonstrated safety and efficacy. Since then, modified injection protocols have been proposed. Adverse events—such as bruising, swelling, hematoma, and corporal rupture—exceed 50% in many studies, but lack of standardization of hematoma severity limits conclusions about the relative safety of protocols. We propose a modification of the standard injection technique that aims to decrease the rates of adverse events. We further describe a hematoma classification rubric that may standardize safety assessment.
Methods
A modified injection procedure, termed the “fan” technique, was employed in the treatment of PD. All men receiving CCh from January 2016 through January 2019 at a single institution were included in an institutional review board (IRB) approved database. Treatment outcomes and adverse events were retrospectively assessed. A three-tiered hematoma classification rubric was devised to standardize reporting of hematoma, which was defined as concurrent bruising and swelling at the site of injection without loss of erection.
Results
Using the fan technique, 152 patients received 1323 injections. Eight hematomas (5.3% of all patients, 0.6% of all injections) were observed. The number of grade I, grade II, and grade III hematomas were 3, 2, and 3, respectively. Bruising or swelling not meeting the definition of hematoma was seen in 54.6% and 27.0% of patients, respectively. There were zero corporal ruptures.
Conclusion
A modified injection technique results in reduced procedural morbidity. A hematoma classification system provides clarity and standardization to the assessment of safety in PD treatment. Further clinical studies with control arms are required to verify these findings.
... The safety and efficacy of CCH in the management of PD have already been tested through several clinical trials enrolling nearly 1500 patients over the last three decades [11][12][13][14][15][16]. In particular, based on the positive findings of two milestone trials, Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies (IMPRESS) 1 and 2, intralesional injection of CCH has emerged as the first medication authorised by the Food and Drug Administration for the conservative management of PD [17,18]. Nevertheless, ventral location of plaque and hourglass deformity were among the major trials' exclusion criteria in the above-mentioned studies, mainly because of the concern of urethral wound. ...
Purpose:
The aim of this study was to evaluate the efficacy of collagenase Clostridium histolyticum (CCH) in patients with Peyronie's disease (PD) suffering from atypical deformities.
Materials and methods:
We retrospectively collected data of patients with atypical penile curvature (PC) secondary to PD. All patients underwent a modified treatment protocol, consisting of 3 intralesional injections of 0.9 mg of CCH performed at 4-week intervals at the point of maximum PC. Patients were instructed to follow a strict routine, involving daily modeling of erect penis and stretching at the urinary toilette time, two minutes each. Success was defined as a decrease in PC of ≥20° from baseline.
Results:
Sixty-five patients were included in the analysis. Median age was 59.0 years (interquartile range [IQR], 53.0 to 63.0 years), median curvature 40.0° (IQR, 30.0° to 45.0°) median duration of the disease 12.0 years (IQR, 6.5 to 24.0 years). Fifty-three patients (81.54%) had ventral PC, 7 (10.77%) hourglass PC, and 5 (7.69%) shortening PC. Median changes of PC were -20.0 (IQR, -20.0 to -10.0; p<0.01) in ventral PC, -20.0 (IQR, -20.0 to 0; p<0.01) in hourglass and -15.0 (IQR, -15.0 to -15.0; p<0.01) in shortening PC. At Kruscal-Wallis test, significant differences between groups were not found. The rate of PC success was 56.60% (30/53) in ventral PC, 57.14% (4/7) in hourglass and 20.00% (1/5) in shortening PC (p=0.29). Treatment success was not influenced by characteristics of curvature (odds ratio=0.66; p=0.20).
Conclusions:
CCH intralesional injections could represent an effective therapeutic option for the conservative management of patients with atypical PC.
Introduction
Treatment recommendations for Peyronie's Disease (PD) differ based on whether a patient is in the acute/active versus chronic/stable phase of the disease, yet there are no agreed upon criteria for defining these clinical entities.
Objectives
To review the criteria used to define acute and chronic phase PD in modern PD intervention studies
Methods
We performed a search engine review to identify indexed publications for PD intervention studies and review articles / meta-analyses from the year 2011-2020. Outcomes results were catalogued and summarized across articles. As a result of the substantial heterogeneity of outcome measures and follow-up intervals, meta-analytic techniques were not applied to the data analysis.
Results
We identified a total of 104 studies that met inclusion criteria and had available information for review (n = 79 primary intervention studies; n = 25 review articles/meta-analyses/guidelines). Among the queried studies, we were unable to identify a consensus with respect to the criteria used to define acute and chronic phases of PD. 33% of primary intervention studies did not specifically define their criteria for acute and chronic phase PD, despite referencing these populations as part of the inclusion criteria in many instances. Studies used heterogenous criteria including total symptom duration, duration of “stable” symptoms, and presence/absence of pain.
Conclusion
Due to varying definitions across the literature, we were unable to create a standardized definition of acute and chronic phase Peyronie's in terms of time. Our findings emphasize the need for greater consensus in defining the treatment cohorts with future studies that assess treatment for men with PD.
Piraino J, Chaudhray H, Ames K, et al. A Consistent Lack of Consistency in Defining the Acute and Chronic Phases of Peyronie's Disease: A Review of the Contemporary Literature. Sex Med Rev 2022;10:698–713.
Introduction
Collagenase Clostridium histolyticum (CCH) is the only approved treatment for conservative management of Peyronie’s disease (PD) that has demonstrated efficacy and safety in clinical trials. However, as the standard treatment protocol is time and resource consuming, we are introducing a new CCH treatment protocol with a more cost-effective profile. Our goal is to evaluate its efficacy and safety.
Materials and methods
We included patients with PD in stable phase, with curvatures of 30–90°. Ventral curvatures and complex deformities were excluded. The treatment protocol consists of a full dose of CCH injected along the PD plaque, forming two lines of four injections. Patients were educated in daily penile modeling activities. The need for a new treatment cycle, up to a maximum of 8 cycles or until the 30° curve was decreased, was reevaluated every 4 weeks. Changes in curvature and number of cycles were recorded to evaluate the efficacy. Regarding safety evaluation, treatment-related adverse events (TRAEs) were recorded, including rupture of the corpora cavernosa, penile hematoma, hematuria, and local infection.
Results
Thirty-one patients were treated under the modified protocol. The mean initial curvature was of 49.84 (±15.83)°. Curvature improvement was recorded in 25 patients (80.6%), with a mean absolute reduction of 20.65 (±15.42)° and relative reduction of 44%. The mean curvature after treatment was 30.67 (±17.25)°. Most patients required one (19.4%) or two (54.8%) injections. No patient presented TRAEs.
Conclusions
The results suggest that the modified CCH treatment protocol is effective and safe, but more studies should be carried out to optimize the current standard protocol.
Resumen
Introducción
La colagenasa de Clostridium histolyticum (CCH) es el único medicamento con licencia para el tratamiento conservador en la enfermedad de Peyronie (EP) que ha demostrado eficacia y seguridad en ensayos clínicos. Sin embargo, el protocolo de tratamiento estándar consume tiempo y recursos, por lo que presentamos un nuevo protocolo de tratamiento con CCH con un perfil más rentable. Nuestro objetivo es evaluar su eficacia y su seguridad.
Materiales y métodos
Se incluyeron pacientes con EP en fase estable, con curvaturas de 30-90°. Se excluyeron curvas ventrales y deformidades complejas. El protocolo de tratamiento consiste en una dosis completa de CCH inyectada a lo largo de la placa de EP formando 2 líneas de 4 inyecciones. Se educó a los pacientes en los ejercicios diarios de modelado del pene. La necesidad de un nuevo ciclo de tratamiento fue reevaluada cada 4 semanas hasta un máximo de 8 ciclos o hasta la disminución de la curva de 30°. Para evaluar la eficacia se registraron los cambios en la curvatura y el número de ciclos. Para evaluar la seguridad se registraron los eventos adversos graves relacionados con el tratamiento, incluyendo la rotura de cuerpos cavernosos, hematoma peneano, hematuria e infección local.
Resultados
Un total de 31 pacientes fueron tratados bajo el protocolo modificado. La curvatura inicial media fue de 49,84 (± 15,83) grados. Se registró mejora en la curvatura en 25 pacientes (80,6%), con una disminución media absoluta de 20,65 (± 15,42) grados y relativa del 44%. La curvatura media posterior al tratamiento fue de 30,67 (± 17,25) grados. La mayoría de los pacientes requirieron una (19,4%) o dos (54,8%) inyecciones. Ningún paciente presentó eventos adversos graves relacionados con el tratamiento.
Conclusiones
Los resultados sugieren que el protocolo de tratamiento modificado con CCH es eficaz y seguro, pero se deben realizar más estudios que ayuden a optimizar el protocolo estándar actual.
Purpose of Review
To review the current literature on acute management of traumatic penile fracture, with a specific discussion of those injuries following collagenase clostridium histolyticum (CCH) injections for the treatment of Peyronie’s disease.
Recent Findings
The immediate repair of traumatic penile fracture injury is associated with significantly better prognosis for long-term sexual health. Corporal disruption following CCH administration has several distinct features, and the trend is to manage these patients conservatively in the absence of urethral injury.
Summary
Traumatic penile fracture repair continues to have excellent results when performed immediately following injury. The post-CCH treatment setting portends increased difficulty during surgical management and can be successfully managed in most cases by conservative measures.
Aim
There are a few types of drugs that can be used in the active phase of Peyronie's disease. Methylprednisolone is a corticosteroid with a strong anti‐inflammatory effect. In this study, we aimed to evaluate the effect of intralesional low‐dose methylprednisolone treatment on patients in the active phase of Peyronie's disease.
Patients and Methods
Forty‐eight patients suffering from Peyronie's disease active phase symptoms were included in the study. Methylprednisolone was administered intralesionally for 8 weeks, once per week, at a dose of 40 mg. The injection was applied to the plaques, which causes maximum curvature. Patients were evaluated before and after treatment for plaque size, angle of curvature, and erectile dysfunction according to the International Index of Erectile Function‐5 and Peyronie's Disease Questionnaire.
Results
The mean age of the patients was 61.1 (43‐78) years. The mean duration of the symptoms was 3.4 (0‐9) months. The average plaque size before treatment was 13.6 mm (7.1‐16.8) and after treatment, this value decreased to 10.8 mm (4.3‐14.6) (P: .025). The average scores of Peyronie's Disease Questionnaire elements; symptom severity, penile pain, and bother/discomfort were 12.3, 19.1, and 6.2, respectively, before the treatment. These scores were decreased to 8.9, 9.6, and 4.4, respectively, after treatment. All subgroups of Peyronie's Disease Questionnaire scores were significantly improved after treatment (P: .001, P < .001, P: .045, respectively). No adverse events were observed during or after treatment.
Conclusion
In order to recover the symptoms and signs, new and easily accessible drugs are required for use in the acute period of Peyronie's disease. In this context, treatment with intralesional low‐dose methylprednisolone in acute phase Peyronie's Disease is a promising and safe treatment option.
Background:
Plaque incision and grafting (PEG) is one of the mainstays in surgical therapy for severe penile curvature in Peyronie's disease (PD). Different kinds of grafts are available for covering albugineal defects during PEG, both allografts and xenografts. However, to date none of these proved superior to others.
Objectives:
To compare two different types of xenograft, porcine dermal matrix and bovine pericardium matrix in PEG for PD.
Materials and methods:
From 2010 to 2019, 63 patients with PD underwent PEG, using porcine dermal (n= 25; Group 1) and bovine pericardium (n=38; Group 2) grafts. Long-term outcomes were evaluated through multi-disciplinary questionnaires administration by phone interview. The following items were considered: correction of penile bending, quality of erection, intercourse ability, penile shortening and sensitiveness. Overall satisfaction and impact of surgery on sexual activity and quality of life was also investigated.
Results:
Plaque median (IQR) size was 29 (22-33) mm, and was smaller in Group 1(27.5 vs. 31 mm; p = 0.03). Complete follow up data were available for 53 patients (84%). Considering postoperative outcomes, no differences were found when considering ED rates, penile shortening, sensitiveness, complications and penile streightening (all p>0.1). Patients in Group 2 were more likely to have palpable penile nodules at follow-up(20.6 vs. 0%; p=0.03). However, patient's postoperative sexual life satisfaction was consistent between the two groups, with just 1 (5.3) and 8 (23.5) patients in Group 1 and 2 respectively refferring a worsening in sexual life satisfaction (p=0.2). At follow up, 84.9% of patients that would still undergo surgery for PD, with no statistical difference between the two groups (p=0.4) CONCLUSIONS: Corporoplasty with PEG is an effective treatment for men with PD. Porcine dermal and bovine pericardium xenografts seem to have similar long-term outcomes.
Background
Collagenase clostridium histolyticum is a recognised non‐surgical management for Peyronie’s disease, licensed for use in the UK for patients with a palpable plaque and a curvature deformity of at least 30°. However, it is not currently funded for use within the National Health Service [NHS]. Collagenase clostridium histolyticum has also recently been withdrawn from the European and other markets worldwide, but there is potential for this to be produced off‐patent in the future.
Objectives
To determine if collagenase clostridium histolyticum is cost‐neutral when compared to surgical management within a public health care system, using the NHS as an example.
Materials and methods
Two published protocols for the administration of collagenase in Peyronie’s disease were identified – the ‘IMPRESS protocol’ and the ‘London protocol’. Costs were taken from published NHS literature. Surgical interventions rates after collagenase clostridium histolyticum administration and primary penile plication were taken from published literature. The costs of the two published protocols were calculated with costs of any repeat surgical intervention were included within each protocol per patient cost.
Results
At the current cost per vial of collagenase to the NHS, the IMPRESS protocol per patient costs £3898.83 (150%) more than primary surgery, while the London protocol costs £136.83 (5.3%) more than primary surgery.
Discussion
At a cost of £526.39 per vial, collagenase administered under the London Protocol would be a management option for Peyronie’s disease cost equivalent to primary corrective surgery.
Conclusion
Central funding of collagenase in a public healthcare system would enable the management of Peyronie’s disease to be moved to the outpatient setting. For this to be done at no additional cost to the NHS it would require a cost reduction per vial of collagenase of £45.61, to a cost of £526.39.
Treating men with Peyronie’s disease remains a challenging problem facing clinicians working across urology and sexual medicine fields. Patients can often be left disappointed by current treatment paradigms, and an overall lack of suitable molecular targets has limited the options for novel, effective medical therapy. Managing men with Peyronie’s disease often involves careful counselling alongside multifaceted and possible combination treatments to help improve symptoms whilst ameliorating potential side effects of therapy. We review the latest medical literature and evidence in the contemporary management of Peyronie’s disease.
Recent developments in the shockwave therapies have created a big excitement in the field of sexual medicine. Although the use of low-intensity shockwave therapy in erectile dysfunction became popular in many Men’s Health centers, its role in the treatment of Peyronie’s Disease (PD) has been a subject of debate. This chapter endeavors to perform a literature review pertaining to the impact of shockwave therapy on PD plaques and to evaluate the possible mechanism of action of this treatment modality in the management of PD. Although there are limited data about the beneficial effects of shockwave therapy among patients with PD, future researches may shed a light on the potential clinical use of this treatment in PD.
Introduction: Collagenase clostridium histolyticum (CCH) is the first and only licensed medical treatment for men with Peyronie’s disease (PD). Published literature shows intralesional CCH injection as an effective and safe minimally invasive treatment in a specific subgroup of PD patients.
Areas covered: The authors discuss pharmacodynamics and pharmacokinetics as well as clinical outcomes and safety profile from major CCH studies in PD. All relevant CCH studies published in PubMed and EMBASE databases up to June 2019 were included.
Expert opinion: Given the variability in treatment schedule and drug access coupled with the potential need for further treatment, strict patient selection and the use of adjunctive strategies are key determinants to maximize clinical efficacy of intralesional CCH. Furthermore, longer-term follow-up data on the clinical outcomes, safety and durability of CCH in larger multi-center studies and post-marketing surveillance data are necessary to provide a comparison to other standard PD treatment options.
Background and Objective
Plaque formation ordinarily takes place in the acute phase of Peyronie’s disease. There is no unanimous consent regarding the management of the acute phase of Peyronie’s disease. The objective of this study was to evaluate the advantages of using a single intralesional injection of collagenase Clostridium histolyticum in patients with the active phase of Peyronie’s disease and to assess its effect on disease progression by reducing penile curvature and ameliorating pain during sexual intercourse.Methods
Sexually active men aged older than 18 years with the acute phase of Peyronie’s disease were enrolled. All patients received treatment with a single intralesional injection of collagenase Clostridium histolyticum. The primary outcome of the study was the change in penile curvature after treatment while secondary outcomes were the change in sexual function (International Index of Erectile Function [IIEF-5]) and in the Peyronie Disease Questionnaire (PDQ) and its sub-scores, PDQ-PS (psychological symptoms), PDQ-PP (penile pain) and PDQ-BD (bother disease).ResultsOverall, 74 patients were enrolled. Mean penile curvature at baseline was 41.1° ± 12.2°. The mean changes before and at the 3-month evaluation in terms of penile curvature, Visual Analog Scale score at rest, and Visual Analog Scale score during intercourse were − 19.3 ± 8.4 (p < 0.0001), − 0.8 ± 1.1 (p < 0.0001) and − 3.8 ± 0.9 (p < 0.0001) with the benefit persisting also after 6 months. Moreover, improvements of mean IIEF-5 score (1.1 ± 0.9, p = 0.03; 0.9 ± 0.5, p = 0.02), PDQ-PS (− 2.7 ± 2.2; − 2.5 ± 2.0, p = 0.01), PDQ-PP (− 1.2 ± 1.6; − 1.1 ± 1.2, p = 0.02) and PDQ-BD (− 3.8 ± 3.4; − 3.5 ± 3.1, p = 0.001) were observed 3 and 6 months after the end of treatment, respectively. At the multivariable regression analysis, the time since disease onset (modelled with non-linear terms) and baseline curvature were independently associated with the degree of curvature improvement (coefficient: 0.30; 95% confidence interval 0.16–0.44) after a single intralesional injection (all p < 0.03).Conclusions
Although intralesional therapy with collagenase Clostridium histolyticum is not yet indicated for the acute phase of Peyronie’s disease, these preliminary results suggest the effectiveness of this minimally invasive option by improving penile curvature and IIEF-5 and PDQ scores.
Background
A subset of patients with Peyronie's disease (PD) treated with collagenase clostridium histolyticum (CCH) experience persistent bother and some require surgery.
Aim
We characterize patients experiencing persistent bother after CCH treatment and identify associations and predictors of surgical intervention/outcomes.
Methods
We retrospectively identified patients with PD from October 2014 to October 2019 and identified those presenting with persistent bother after CCH treatment by other urologists. Intracavernosal injection and penile Doppler ultrasonography were performed, and subsequent interventions/outcomes were recorded. Baseline characteristics were compared with Student t-test and chi-square test. Predictors of surgical intervention and complications were assessed using multivariable logistic regression.
Outcomes
The primary outcome was surgery after CCH treatment. Secondary outcomes included worsened erectile function, sensory deficits, and penile length change.
Results
Of 573, 67 (11.7%) patients with PD had undergone prior CCH treatment with median 6 injections (range 2–24). Mean post-CCH PD Questionnaire bother score was 10.1 (SD: 3.1), and total International Index of Erectile Function-5 was 15.3 (SD: 8.7). Mean PD duration was 27.8 (SD: 35.7) months, with a mean composite curvature (MCC) of 69.0° (SD: 33.8) measured after injection. Of 67, 44 (65.7%) patients had MCC >60°. Of 67, 52 (77.6%) patients had indent, narrowing, or hourglass and 26 (38.8%) had hinge effect (buckling of the erect penis with axial pressure) on examination. Calcification was identified in 26 of 67 (38.8%) patients, with grade 3 calcifications comprising 6 of 23 (26.1%) patients. Of 67, 33 (49.3%) patients underwent surgery, with 20 (60.1%) undergoing partial plaque excision and grafting with/without tunica albuginea plication, 6 (18.2%) undergoing tunica albuginea plication alone, and 7 (21.2%) undergoing penile prosthesis with plaque incision and grafting. Surgical patients had greater mean curvature (82.6 vs 55.4, P = .001) and were more likely to have hinge (54.5% vs 20.6%, P = .005). On multivariable analysis, MCC ≥60° predicted patient’s decision for surgery (odds ratio: 2.99, P < .01, 95% confidence interval: 1.62–4.35). There were no associations between surgical complications and number of injections or CCH-associated adverse events.
Clinical Implications
Patients presenting with persistent bother after CCH treatment often have narrowing and calcifications (despite calcifications being a contraindication to CCH treatment), and those who have hinge or severe curvature are more likely to undergo surgery with low rates of complications.
Strengths/Limitations
This study's generalizability is limited by selection bias, but useful data are provided for patient counseling.
Conclusion
Patients with persistent bother after CCH treatment had high rates of indentation/narrowing, plaque calcifications, and MCC >60° at completion of CCH treatment. Surgical intervention is more common with hinge and is safe and feasible in these patients, with low rates of complications. These findings suggest possible negative prognostic factors for CCH treatment, which merit further investigation.
Bajic P, Wiggins AB, Ziegelmann MJ, et al. Characteristics of Men With Peyronie's Disease and Collagenase Clostridium Histolyticum Treatment Failure: Predictors of Surgical Intervention and Outcomes. J Sex Med 2020;XX:XXX–XXX.
Introduction and objective:
The assessment of penile curvature is a key component of hypospadias surgery, as it often determines if a one- or two-stage procedure should be performed. The objective of this study was to compare unaided visual inspection (UVI) against goniometry estimations of ventral penile curvature (VC) among pediatric urologists.
Methods:
A total of nine different penile models (1.5 cm wide and 5-6 cm long) representing each decile of curvature from 10° to 90° were created. The nine models were divided in two groups: one with five models (group 1: 10°, 30°, 50°, 70°, and 90°) and the other with four models (group 2: 20°, 40°, 60°, and 80°). Each subject measured the VC of each model in group 1 using one method (i.e. UVI) and the curvature of each model in group 2 using the other method (i.e. goniometry). The next subject then used the opposite method for group 1 (goniometry) and group 2 (UVI), and so on, alternating the methods used to measure each group in between the subjects (Figure). The mean error (difference in between the true curvature and the subject estimation) was compared in between the two measurement methods (UVI and goniometry). A statistician calculated that 20-30 subjects would be needed to detect more than 10° difference in between the methods.
Results:
A total of 25 subjects were recruited for the study (24 pediatric urologists and 1 adult urologist). Mean errors for all degrees of penile curvature and methods ranged from 3.5° (90° model) to 13.6° (30° model). The mean error was not statistically different in between UVI and goniometry methods for any degree of curvature. A subgroup analysis of only goniometry estimations comparing subjects with and without prior experience with goniometry showed a statistically significant difference only for the 60° model. If choosing the correct surgery depended on determining if the curvature was ≤30° or >30°, all subjects would have chosen the right surgery for all except the 20°, 30°, and 40° models, where wrong surgery was chosen in 6/25, 15/25, and 7/25, respectively.
Conclusions:
In this preliminary study, goniometry was not superior to UVI at estimating VC. There is pressing need in the field of hypospadias surgery to develop a tool that can measure VC in a reproducible and reliable fashion.
Introduction:
Surgery remains the gold standard for the correction of penile deformities secondary to Peyronie's disease (PD). Nevertheless, there is no published data on the surgical treatment of PD in older men.
Aim:
Considering the aging national and international population, we sought to evaluate the pre-operative characteristics and surgical outcomes of men aged 65 or older who underwent surgical treatment for PD at our tertiary care institution.
Methods:
We retrospectively reviewed the charts of all men 65 years or older who underwent surgery for PD from January 2010 to September 2017. We compared men who underwent penile prosthesis implantation with straightening maneuvers (PP+SMs), tunica albuginea plication (TAP), and plaque partial excision with grafting (PEG).
Main outcome measure:
The main objective of this study was to find the baseline pre-operative patient characteristics and postoperative patient-reported outcomes.
Results:
A total of 86 men with a median age of 68 years underwent surgery during the study period. 39 men underwent PP+SM (45%), 25 men a TAP (29%), and 22 men a PEG (26%). The mean curvature for all men was 59.9 ± 22.0° (range 0-105°). Those who underwent a PEG had a mean ± SD degree of curvature of 78.6 ± 16.6°, significantly higher than those who underwent PP+SM or TAP (49.1 ± 20.2° and 61.4 ± 17.4°, respectively; P < .001). Moreover, men who underwent a PEG had significantly more complex penile deformities (eg, narrowing with hinge effect) and better reported baseline erectile function compared with men who underwent PP+SM or TAP. Overall, 95% of all men reported having a functionally straight penis postoperatively with 94% engaging in penetrative intercourse at last follow-up. Overall, patient-reported satisfaction was 85% with a median follow-up of 43.5 months.
Clinical implications:
Our findings suggest that the surgical treatment of PD in older men is safe, effective, and associated with high patient satisfaction. Although this represents a surgical series susceptible to selection bias, it underscores the importance of patient selection and counseling in achieving good surgical outcomes.
Strengths & limitations:
Our study is the first to report on outcomes of surgical treatment of PD in an elderly patient population with relatively long-term follow-up. Our limitations include a small sample size, single operating surgeon, and the lack of a younger comparison group.
Conclusion:
Despite an aging global population, surgery remains a viable and reliable option for the properly selected and counseled older men with PD. Abdelsayed GA, Setia SA, Levine LA. The Surgical Treatment of Peyronie's Disease in the Older Man: Patient Characteristics and Surgical Outcomes in Men 65 and Older. J Sex Med 2019;16:1820-1826.
Several strategies to optimize penile length in the presence of Peyronie’s Disease (PD) have been described so far. In case of severe curvature and preserved erectile function, plaque incision/excision (PIG/PEG) are advisable in order to maximize penile length, despite the risk of postoperative erectile dysfunction (ED), recurrent curvature, or penile shortening. For men with PD deformities associated to a certain degree of ED several lengthening techniques associated to penile prosthesis (PPI) implantation can be considered. Because of the potential postoperative complications, the indication must be balanced between patient’s risk factors and surgeon’s experience. Furthermore, adjuvant surgeries, such as prepubic V-Y plasty, suspensory ligament release, suprapubic lipectomy, and ventral phalloplasty, can be performed simultaneously or in a staged fashion to maximize the outcomes. Restoration a decent penile length in the case of a severe PD represents a real challenge for reconstructive surgeons. We present a systematic review of the literature on the current practices for penile lengthening in severe PD, providing the reader with a practical overview on the existing surgical strategies and their surgical and functional outcomes.
Purpose
The introduction of collagenase Clostridium histolyticum (CCH) as the first and only FDA-approved non-surgical treatment for Peyronie’s disease (PD) has been an important step in its management. Our aim is to provide an overview of the historical origins of CCH and its development through FDA approval and beyond for the treatment of PD.
Methods
A PubMed search using the terms Peyronie OR Peyronie’s AND collagenase and limited to clinical research studies resulted in 24 articles that were examined for the current review.
Results
PD is a connective tissue disorder of the penile tunica albuginea involving fibrotic penile plaques that cause abnormal curvature and, in many cases, erectile pain. Although the exact mechanism and underlying pathophysiology are not well characterized, the known lability of these plaques to exogenous bacterial collagenase combined with a lack of effective medical therapies led to the development of CCH as an evidence-based treatment of PD. The initial discovery of collagenase was followed by in vitro studies on PD plaque tissue and following the phase 3 IMPRESS trial culminated in FDA approval of CCH in 2013. Future directions in CCH therapy include improved patient selection, use in acute phase PD, adjuvant and combination therapies, and novel delivery mechanisms.
Conclusion
CCH provides an effective non-surgical treatment option for men with PD. We have traced the development of CCH in the treatment of PD from the earliest in vitro investigations to comprehensive multi-study meta-analyses confirming its highly rated efficacy when compared to other historical non-surgical remedies.
Background:
Previous studies of penile traction therapy (PTT) devices have demonstrated limited/no efficacy when combined with intralesional therapies for Peyronie's disease (PD). Recently, randomized data have demonstrated the efficacy of a novel PTT device, RestoreX, developed in cooperation with the Mayo Clinic, in men with PD.
Aim:
To assess the safety and efficacy of treatment with the RestoreX device plus collagenase Clostridium histolyticum (CCH) compared with CCH alone and CCH with other PTT devices.
Methods:
A prospective registry has been maintained of all men undergoing CCH injections for PD between March 2014 and January 2019. Assessments were performed at baseline, during each series, and after completion of treatment. Those completing therapy (8 injections or sooner if satisfied) were categorized into group 1 (CCH alone), group 2 (CCH plus any PTT device other than RestoreX), or group 3 (CCH plus RestoreX).
Outcomes:
Changes in penile length, curvature, and subjective perception and the occurrence of adverse events.
Results:
Of 287 men with data on PTT use, 113 had completed therapy with all objective data available and compose the current cohort. Baseline demographic and pathophysiological variables were similar among the 3 groups except penile length and previous PD medications. Following treatment, group 3 demonstrated significantly greater improvements in curvature (mean, 20.3°/31% for group 1, 19.2°/30% for group 2, and 33.8°/49% for group 3), length (-0.7 cm/-4%, -0.4 cm/-2%, and +1.9 cm/+17%, respectively), and subjectively estimated curvature improvement (44%, 32%, and 63% respectively), despite shorter daily PTT use (0.9 vs 1.9 hours/day). Group 3 was more likely than the other groups to experience ≥20°, ≥20%, and ≥50% curvature improvements, ≥1 cm length gain, and ≥20% length improvement. All results were statistically significant for group 3 versus groups 1 and 2, but not between groups 1 and 2, even after controlling for baseline features and isolating a subset of ≥3 hours/day PTT use (group 2). Group 3 was 6.9 times more likely to achieve ≥20° curvature improvement, and 3.5 times more likely to achieve ≥50% curvature improvement, and 10.7 times more likely to experience ≥20% length improvement. Adverse events were similar among the 3 groups.
Clinical implications:
Use of the RestoreX device enhances mean curvature outcomes by 71% and increases penile length in men with PD receiving CCH therapy.
Strengths & limitations:
Study strengths include a prospective registry, consistent assessments, the largest single-site series with complete posttreatment outcomes reported to date, the largest PTT series reported to date, and a true-to-life clinical design. Limitations include the nonrandomized methodology and single-site setting.
Conclusion:
The combination of RestoreX and CCH is associated with significantly greater curvature and length improvements compared with CCH alone or CCH with other PTT devices. Alom M, Sharma KL, Toussi A, et al. Efficacy of Combined Collagenase Clostridium histolyticum and RestoreX Penile Traction Therapy in Men with Peyronie's Disease. J Sex Med 2019;16:891-900.
Résumé
La maladie de La Peyronie est une pathologie grave et invalidante avec une prévalence hautement sous évaluée. Le Xiapex® est le premier traitement disponible en France ayant reçu une AMM avec une utilisation possible à tout stade de la maladie. Ce traitement, très attendu en France, permet d’enrichir l’arsenal thérapeutique préexistant. Cependant son coût et l’absence de prise en charge par la sécurité sociale risque d’être un frein à sa prescription (800 euros l’injection). Son usage nécessite une formation obligatoire pour tout urologue souhaitant le prescrire.
Die Induratio penis plastica (IPP) ist ein typisches, aber heterogenes Krankheitsbild mit den klassischen penilen Symptomen Plaquebildung, peniler Schmerz, Deviation, Verkürzung des Penis und erektile Dysfunktion. Die Ätiologie ist unklar. Mikrotraumen werden als Ursache einer nachfolgenden, evtl. genetisch bedingten atypischen Wundheilung mit Bildung eines fibrotischen unelastischen Narbengewebes im Bereich der Tunica albuginea diskutiert. Eine kausale medikamentöse Therapie ist deshalb nicht möglich, obwohl vielfältige konservative Therapieoptionen klinisch eingesetzt werden. Die chirurgische Korrektur einer Penisverkrümmung ist in der Phase der stabilen Erkrankung das primäre Operationsziel. Unterschiedliche Operationsverfahren werden abhängig von Deviationsgrad, Penislänge und erektiler Funktion durchgeführt. Dieser Artikel gibt eine Übersicht über den aktuellen Stand der Diagnostik sowie konservativer und chirurgischer Therapieoptionen.
Background
An examination of potential racial variations between Caucasian American (CA) and African American (AA) men in the efficacy and safety of collagenase clostridium histolyticum (CCH) in the treatment of Peyronie’s disease (PD).
Methods
We retrospectively reviewed the records for all patients treated with CCH for PD between 04/2014 and 05/2017. Patients were divided into two groups based on their self-reported race. The primary outcomes of interest were final change in curvature after CCH treatment regardless of number of CCH cycles received, and frequency of treatment-related adverse events (TRAEs).
Results
A total of 159 patients were included in the study, of which 146 (91.8%) were CA while 13 (8.2%) were AA. Mean duration of PD was 28.3 months for CA patients and 16.8 months for CA patients (P=0.436). There was no significant difference in final change in curvature CA and AA patients (15.9° vs. 13.1° respectively, P=0.445). There was no statistically significant difference in frequency of TRAEs between CA patients (17, 12%) and AA patients (0, 0%) (P=0.208).
Conclusions
Although racial variations in efficacy and safety of CCH in patients with PD have not been addressed in the literature, preliminary results from our study suggest that CCH therapy may be equally efficacious and safe in both CA and AA men. There was no statistically significant difference in final change in curvature, International Index of Erectile Function (IIEF) scores, penile length, or TRAEs after CCH treatment between CA and AA patients.
Peyronie’s disease (PD) is an inflammatory disorder characterized by an abnormal collagen deposition in the tunica albuginea
of the penis, leading to fibrous and non-compliant plaques that can impede normal erection. Although pharmacological
treatments are available, only intralesional injection therapy and surgical reconstruction have demonstrated tangible clinical
efficacy in the management of this condition. Intralesional injection of collagenase clostridium histolyticum (CCH) has come to
the forefront of minimally invasive treatment of PD. In this review, the authors provide an update on the safety, efficacy, and
indications for CCH. The efficacy of CCH will be assessed on the basis of improvement in the severity of penile fibrosis, curvature,
and pain. Numerous well-designed clinical trials and post-approval studies involving more than 1,500 patients have consistently
demonstrated the efficacy and tolerability of CCH in the treatment of PD. CCH significantly decreases penile curvature and
plaque consistency, as well as improves quality of life. Post-approval studies continue to demonstrate the efficacy of CCH despite
broader inclusion criteria for treatment, such as the case with acute phase disease and atypical plaque deformities (i.e., ventral
plaques, hourglass narrowing). CCH continues to be the gold standard for non-surgical management of stable phase PD, in the
absence of strong evidence supporting oral therapy agents and ongoing evaluation of extracorporeal shockwave therapy.
However, recent studies are beginning to provide precedent for the use of CCH in the management of acute phase and atypical
PD.
Introduction:
Peyronie's disease (PD) is a common condition that results in penile deformity, which makes sexual intercourse difficult or impossible, and causes psychological, emotional, and relationship difficulties for the man affected and his partner. Collagenase Clostridium histolyticum (CCH; Xiapex, Xiaflex) is the first licensed non-surgical treatment option for PD. The safety and efficacy have been demonstrated in two large phase III randomized controlled trials (IMPRESS I and IMPRESS II).
Aim:
To review the safety and efficacy of CCH and to introduce a new shortened modified protocol for CCH that was developed by the authors to decrease the cost and duration of treatment.
Methods:
A review of the medical literature on CCH for inclusion in this review was obtained by searching the PubMed (from 1946) and Medline (from 1946) medical databases and from the screening of relevant bibliographies. The search terms Xiapex, Xiaflex, collagenase Clostridial histolyticum, and Peyronie's disease were used. Clinical trials in men with PD and scientific articles relating to pharmacologic data were included in the review. When possible, large, randomized, and well-designed trials were selected.
Main outcome measures:
Changes in the angle of penile curvature and in the Peyronie's Disease Questionnaire domains.
Results:
The clinical trials demonstrate the safety and efficacy of CCH in the treatment of PD. The new modified protocol developed by the authors is as safe and effective as the protocol used in the clinical trials.
Conclusion:
CCH is the first licensed non-surgical treatment for PD. Its safety and efficacy have been demonstrated in large well-designed clinical trials. The new shortened modified protocol decreases the cost and duration of the treatment without compromising the safety and efficacy of the drug. This alteration will allow more patients to benefit from CCH. Abdel Raheem A, Johnson M, Abdel-Raheem T, et al. Collagenase Clostridium histolyticum in the Treatment of Peyronie's Disease-A Review of the Literature and a New Modified Protocol. Sex Med Rev 2017;X:XXX-XXX.
The purpose of this guideline is to provide a clinical framework for the diagnosis and treatment of Peyronie's disease (PD).
A systematic review of the literature using the Pubmed, Embase, and Cochrane databases (search dates 1/1/1965 to 1/26/15) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of PD. The review yielded an evidence base of 303 articles after application of inclusion/exclusion criteria.
The systematic review was used to create guideline statements regarding treatment of PD. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high quality evidence; high certainty), B (moderate quality evidence; moderate certainty), or C (low quality evidence; low certainty). Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional consensus statements related to the diagnosis of PD are provided as Clinical Principles and Expert Opinions due to insufficient published evidence.
There is a continually expanding literature on PD; the Panel notes that this document constitutes a clinical strategy and is not intended to be interpreted rigidly. The most effective approach for a particular patient is best determined by the individual clinician and patient in the context of that patient's history, values, and goals for treatment. As the science relevant to PD evolves and improves, the strategies presented here will be amended to remain consistent with the highest standards of clinical care.
Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Objectives
To examine the efficacy of intralesional collagenase clostridium histolyticum (CCH) in defined subgroups of subjects with Peyronie's disease (PD).Subjects and Methods
The efficacy of CCH compared with placebo from baseline to week 52 was examined in subgroups of subjects from the Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies (IMPRESS) I and II, defined by: severity of penile curvature deformity at baseline (30°-60° [n=492] and 61°-90° [n=120]); PD duration (1 to ≤2 [n=201], >2 to ≤4 [n=212], and >4 years [n=199]); degree of plaque calcification (no calcification [n=447], noncontiguous stippling [n=103], and contiguous calcification that did not interfere with the injection [n=62]); and baseline erectile function (International Index of Erectile Function [IIEF] 1-5 [n=22], 6-16 [n=106], and ≥17 [n=480]).ResultsReductions in penile curvature deformity and PD symptom bother were observed in all subgroups. Penile curvature deformity reductions were significantly greater for CCH vs placebo for: baseline penile curvature 30°-60° and 61°-90°; disease duration >2 to ≤4 years and >4 years; no calcification; and IIEF ≥17 (high IIEF erectile function) (P < .05 for all). PD symptom bother reductions were significantly greater in the CCH group for: penile curvature 30°-60°; disease duration >4 years; no calcification; and IIEF 1-5 (no sexual activity) and ≥17 (P < .05 for all).Conclusions
In this analysis, the clinical efficacy of CCH treatment for reducing penile curvature deformity and PD symptom bother was demonstrated across subgroups. In the IMPRESS I and II studies overall, AEs were typically mild or moderate, although treatment-related serious AEs, including corporal rupture or penile hematoma, occurred. Future studies could be considered to directly assess the efficacy and safety of CCH treatment in defined subgroups of PD patients, with the goal of identifying predictors of optimal treatment success.This article is protected by copyright. All rights reserved.
Purpose:
IMPRESS (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies) I and II examined the clinical efficacy and safety of collagenase Clostridium histolyticum intralesional injections in subjects with Peyronie disease. Co-primary outcomes in these identical phase 3 randomized, double-blind, placebo controlled studies included the percent change in the penile curvature abnormality and the change in the Peyronie disease questionnaire symptom bother score from baseline to 52 weeks.
Materials and methods:
IMPRESS I and II examined collagenase C. histolyticum intralesional injections in 417 and 415 subjects, respectively, through a maximum of 4 treatment cycles, each separated by 6 weeks. Men received up to 8 injections of 0.58 mg collagenase C. histolyticum, that is 2 injections per cycle separated by approximately 24 to 72 hours with the second injection of each followed 24 to 72 hours later by penile plaque modeling. Men were stratified by baseline penile curvature (30 to 60 vs 61 to 90 degrees) and randomized to collagenase C. histolyticum or placebo 2:1 in favor of the former.
Results:
Post hoc meta-analysis of IMPRESS I and II data revealed that men treated with collagenase C. histolyticum showed a mean 34% improvement in penile curvature, representing a mean ± SD -17.0 ± 14.8 degree change per subject, compared with a mean 18.2% improvement in placebo treated men, representing a mean -9.3 ± 13.6 degree change per subject (p <0.0001). The mean change in Peyronie disease symptom bother score was significantly improved in treated men vs men on placebo (-2.8 ± 3.8 vs -1.8 ± 3.5, p = 0.0037). Three serious adverse events (corporeal rupture) were surgically repaired.
Conclusions:
IMPRESS I and II support the clinical efficacy and safety of collagenase C. histolyticum for the physical and psychological aspects of Peyronie disease.