Treatment of Peyronie's Disease With Collagenase Clostridium histolyticum and Vacuum Therapy: A Randomized,Open-Label Pilot Study

BackgroundCollagenase Clostridium histolyticum (CCH) is indicated for the treatment of penile curvature in adult men with Peyronie's disease (PD) with palpable plaque and curvature deformity of at least 30° at the start of therapy.AimTo evaluate the efficacy and safety of CCH plus vacuum-pump therapy with and without penile modeling for the management of PD.MethodsAdult men with PD and penile curvature of at least 30° were randomly assigned to receive CCH 0.58 mg plus vacuum therapy alone (n = 15) or with penile plaque modeling (n = 15). Patients received no more than four treatment cycles (cycle = ∼6-week duration), each consisting of two intralesional injections of CCH administered 24 to 72 hours apart. Vacuum therapy was applied twice daily from 14 days after the second injection of each cycle until the following cycle. Modeling was performed 24 to 72 hours after the second injection of each cycle.OutcomesThe primary end point was change in penile curvature from baseline to week 36; additional end points included changes in Peyronie's Disease Questionnaire (PDQ) domain scores, composite response (≥20% decrease in penile curvature and decrease in PDQ bother score ≥ 1 point), and global response (small but important, moderate, or much improvement in the Global Assessment of PD).ResultsAt week 36, improvement in penile curvature from baseline was similar in the two groups (mean change from baseline = −23.7° [SD = 10.9] for CCH + vacuum + modeling and −23.3° [SD = 7.2] for CCH + vacuum; between-group difference = −0.3°, 95% CI = −7.3 to 6.6). Improvements in most PDQ domains, including bother, were observed from baseline to week 36 in the two groups. Most patients were composite (66.7% and 84.6% with CCH + vacuum + modeling and CCH + vacuum, respectively) and global (86.7% and 92.3%, respectively) responders. The most common adverse events were penile contusion, penile swelling, and penile pain.Clinical ImplicationsVacuum-pump therapy administered alone or in combination with modeling after CCH treatment could improve PD symptoms.Strengths and LimitationsThis was a pilot study with a small sample and limited follow-up duration.ConclusionCCH and vacuum-pump therapy (alone or combined with modeling) could be an appropriate consideration for men with PD and warrants further investigation.Ralph DJ, Abdel Raheem A, Liu G. Treatment of Peyronie's Disease With Collagenase Clostridium histolyticum and Vacuum Therapy: A Randomized, Open-Label Pilot Study. J Sex Med 2017;14:1430–1437.     

Surgical Correction of Persistent Peyronie's Disease Following Collagenase Clostridium Histolyticum Treatment

IntroductionCollagenase clostridium histolyticum (CCH) is an Food and Drug Administration‐approved intralesional injection for treatment of Peyronie's disease (PD) that has been shown to reduce penile curvature deformity and PD symptom bother in phase 2b and phase 3 placebo‐controlled clinical trials. For some patients, nonsurgical treatment with CCH may not sufficiently improve penile curvature, and surgical correction may be pursued following CCH therapy.AimThis study aims to examine intraoperative and postsurgical outcomes of surgical correction of persistent penile curvature in patients with PD who had previously received CCH.MethodsRetrospective chart review was used to identify patients with PD who had received CCH intralesional injection within either the phase 2b or phase 3 CCH clinical trials and then underwent surgical correction due to remaining penile curvature. Surgical techniques used were partial plaque excision and grafting (PEG) and/or tunica albuginea plication (TAP).Main Outcome MeasuresPrimary assessments included pre‐ and postsurgery penile curvature, erectile rigidity, stretched penile length, intraoperative time, and occurrence of adverse events.ResultsSeven men were identified who underwent surgical straightening with TAP or PEG following CCH treatment. Mean number of days from the final CCH injection to surgery was 182 (standard deviation 118; median 127 days). Average penile curvature prior to surgical straightening was 58°. No anatomical difficulties or complications secondary to the effects of prior CCH treatment occurred during surgery. Intraoperative time was representative of standard TAP and PEG surgeries (range 88–146 minutes). All men reported penile curvature <20° postsurgery. One patient experienced a postsurgery subgraft hematoma that required aspiration. There were no postsurgery reports of decreased penile sexual sensation and no occurrence of vascular compromise or decreased penile rigidity.ConclusionThis initial case series supports the hypothesis that prior CCH treatment is not a contraindication to PEG or TAP surgery in the treatment of penile curvature in patients with PD. Levine LA and Larsen SM. Surgical correction of persistent Peyronie's disease following collagenase clostridium histolyticum treatment. J Sex Med 2015;12:259–264.     

Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie’s Disease

BackgroundPeyronie’s disease (PD), defined as the abnormal formation of fibrous plaque(s) in the tunica albuginea of the penis, is a chronic condition that afflicts 3% to 13% of the US male population; there is no current research on the efficacy and safety of collagenase Clostridium histolyticum (CCH) in the treatment of acute phase PD.AimTo examine the efficacy and safety of CCH in the treatment of acute-phase PD.MethodsWe retrospectively reviewed the records for all patients treated with CCH for PD from April 2014 through April 2017. Patients who reported penile pain and duration of PD no longer than 12 months at presentation qualified as being in the acute phase of PD. The primary outcomes of interest were final changes in curvature after CCH treatment regardless of the number of CCH cycles received and frequency of treatment-related adverse events.OutcomesParameters of efficacy and safety were compared between acute- and stable-phase PD.ResultsA total of 162 patients were included in the study, of which 36 (22%) qualified as having acute-phase PD (group 1) and the remaining 126 (78%) qualified as having stable-phase PD (group 2). Median duration of PD was 8.5 months (range = 1–12) for group 1 and 18 months (range = 1–492) for group 2. There was no significant difference in final change in curvature between the acute and stable phases of PD (16.7° vs 15.6°; P = .654). There was no statistically significant difference in frequency of treatment-related adverse events between the acute phase (4 patients, 11%) and the stable phase (12 patients, 10%; P = .778).Clinical ImplicationsCCH therapy is as safe and efficacious in acute-phase PD as it is in stable-phase PD.Strengths and LimitationsThis is the first report that assesses the safety and efficacy of CCH therapy focusing on acute-phase PD. This study was composed of a large cohort of patients receiving CCH therapy in acute- and stable-phase PD. Limitations include bias associated with retrospective studies, a small sample, and a single-center setting.ConclusionsAlthough CCH is not clearly indicated for treatment during the acute phase of PD, these results suggest that CCH use during this phase can be effective and safe. There was no statistically significant difference in final change in curvature or treatment-related adverse events after CCH therapy delivered between the acute and stable phases of PD.Nguyen HMT, Anaissie J, DeLay KJ, et al. Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie’s Disease. J Sex Med 2017;14:1220–1225.     

Baseline Characteristics from an Ongoing Phase 3 Study of Collagenase Clostridium Histolyticum in Patients with Peyronie's Disease

IntroductionPeyronie's disease (PD) is a localized penile collagen disorder of the tunica albuginea associated with significant physical deformity and psychological impairment. Current understanding of pretreatment characteristics in patients with chronic PD is limited by small samples, varied quality of assessments, and the lack of a PD‐specific, validated measure of the psychosexual impact of PD.AimsReporting baseline demographic and disease characteristics of the large multinational cohort of subjects with chronic PD who participated in the collagenase clostridium histolyticum (CCH, an investigational intralesional injection and minimally invasive intervention) phase 3 clinical study program. Findings from well‐defined assessments, including the Peyronie's Disease Questionnaire (PDQ), the first validated PD‐specific patient‐reported measure of psychosexual impact, are reported.MethodsSubjects included men ≥18 years old with PD symptoms ≥12 months and penile deformity between 30° and 90°. Analysis data included demographics, disease history, and psychosexual impact.Main Outcome MeasuresPenile deformity, disease symptoms, the International Index of Erectile Function, and the PDQ were assessed.ResultsEight hundred thirty‐two subjects were enrolled from 64 sites across the United States and Australia. The mean age was 57.7 years; mean PD duration was 4.1 years. The majority of subjects had penile deformity ≤60° (77.3%); mean penile deformity was 50.5°. Subjects reported having intercourse a mean of 10.2 times in the previous 3 months, 70.8% reported difficulty in performing vaginal intercourse, and 80.4% reported less frequent vaginal intercourse. Approximately 71.5% of subjects with severe (>60°) and 58.1% of subjects with mild/moderate (≤60°) penile deformity were “very bothered” or “extremely bothered” upon last look at their erect penis (P = 0.0041), as measured by the PDQ.ConclusionsThese data add to the body of knowledge regarding the clinical impact of chronic phase PD, including the PD-specific patient-reported psychosexual symptoms, using a large multinational chronic PD cohort in the CCH phase 3 clinical program. Gelbard M, Hellstrom WJG, McMahon CG, Levine LA, Smith T, Tursi J, Kaufman G, and Goldstein I. Baseline characteristics from an ongoing phase 3 study of collagenase clostridium histolyticum in patients with Peyronie's disease. J Sex Med 2013;10:2822–2831.     

Responsiveness of the Peyronie's Disease Questionnaire (PDQ)

IntroductionIn order to reliably assess treatment effectiveness, patient-reported outcome instruments must demonstrate adequate psychometric properties.AimTo assess the responsiveness of the Peyronie's Disease Questionnaire (PDQ) using data from two Phase 3 trials of collagenase clostridium histolyticum for Peyronie's disease (PD).MethodsBoth trials recruited adult males with PD who were in a stable relationship with a female partner for at least 3 months. Patients completed the PDQ, International Index of Erectile Function (IIEF), and a global assessment of PD (GAPD) questionnaire at baseline and Weeks 24 and 52. Anchor- and distribution-based methods were used to evaluate the responsiveness of the PDQ.Main Outcome MeasurePeyronie's Disease Questionnaire.ResultsThe number of men available with baseline and Week 52 data was 267 for Study 1 and 270 for Study 2. The mean age was 58.0 for Study 1 and 57.4 for Study 2; the majority were white (95.2% and 97.3%, respectively). Mean PDQ subscale change scores from baseline to Week 52 for both studies ranged from −1.5 to −4.6 (P < 0.0001). In Study 1, effect sizes were moderate to large on the Psychological and Physical Symptoms (−0.56) and Symptom Bother subscales (−0.84). For patients with penile pain at baseline, the effect size was large (−1.05) for the Penile Pain subscale. Similar effect sizes were seen in Study 2. The Psychological and Physical Symptoms and Symptom Bother subscales significantly discriminated patient improvement ratings of GAPD and degree of penile curvature at Weeks 24 and 52.ConclusionsThe PDQ is highly responsive to change in men with PD. Coyne KS, Currie BM, Thompson CL, and Smith TM. Responsiveness of the Peyronie's Disease Questionnaire (PDQ). J Sex Med 2015;12:1072–1079.     

Controversies in Sexual Medicine: Is There a Place for Conservative Treatment in Peyronie's Disease?

IntroductionPeyronie's disease (PD) is a relatively common disorder affecting middle aged men. Conservative nonsurgical treatments include oral, topical, and intra-lesional pharmacotherapies, vacuum stretching, and mechanical traction.MethodsFour people with expertise and/or interest in the area of PD were asked to contribute their opinions with regard to the safety and efficacy of nonsurgical conservative treatments.Main Outcome MeasureTo provide food for thought, discussion, and possible further research in a poorly discussed area of sexual medicine.ResultsOf the four experts writing on the topic, one believes a combination of medical therapy and penile traction has positive potential for curvature. Another feels that although medical therapies have potential to alleviate pain, there is little evidence to show that they help with curvature or that penile traction helps. A third expert proposes dividing the disease into phases, where patients in the acute phase may benefit from conservative therapy, whereas patients whose disease is stable require surgical intervention. The last expert agrees that the therapy should depend on the stage of the disease, but believes like the first expert that there is a role for traction therapy for patients with stable disease.ConclusionThere is a need for guidelines for nonsurgical therapies for patients with PD, but there is a paucity of evidence as to their efficacy. Vardi Y, Levine LA, Chen J, Hatzimouratidis K, and Sohn M. Is there a place for conservative treatment in Peyronie's disease? J Sex Med 2009;6:903–909.     

Predictors of Curvature Improvement in Men With Peyronie's Disease Treated With Intralesional Collagenase Clostridium Histolyticum

IntroductionPenile 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.AimTo identify predictor factors associated with improvements of penile curvature outcomes in men with PD treated with CCH.MethodsWe 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.OutcomesDegrees of the curvature changes between the baseline and after the cycles of CCH.ResultsA 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).Clinical ImplicationsWe 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.Strengths and LimitationsThis 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.ConclusionPenile 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.     

Clinical Safety and Effectiveness of Collagenase Clostridium Histolyticum Injection in Patients with Peyronie's Disease: A Phase 3 Open‐Label Study

IntroductionCollagenase clostridium histolyticum (CCH; Xiaflex, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA, USA) is a Food and Drug Administration‐approved, intralesional treatment for Peyronie's disease (PD).AimThe aim of this study was to assess the safety and effectiveness of CCH in the treatment of PD.MethodsThis phase 3, open‐label study enrolled subjects who were CCH‐naïve, were enrolled in a previous pharmacokinetic study, or had received placebo in an earlier phase 2 CCH study. Each treatment cycle included two intralesional injections of CCH 0.58 mg, approximately 24–72 hours apart, and plaque modeling 24–72 hours after the second injection of each cycle. The treatment cycle was repeated after 6 weeks for ≤4 treatment cycles.Main Outcome MeasuresThe co‐primary end points were the mean percent change in penile curvature deformity and the mean improvement in PD bother score (range 0–16) from baseline to week 36.ResultsOf the 347 subjects treated with ≥1 injection, 238 had both a penile curvature measurement and a Peyronie's Disease Questionnaire response at baseline and ≥1 subsequent time point. Mean baseline penile curvature deformity was 53.0° and mean PD symptom bother was 7.3. Statistically significant mean improvements from baseline to week 36 were observed in both penile curvature deformity (34.4% [95% confidence interval {CI}, 31.2%, 37.6%]) and PD symptom bother score (3.3 [95% CI, 2.8, 3.7]). Most adverse events (AEs) were mild or moderate in severity and local to the penis. There were three serious treatment‐related AEs, two penile hematomas and one corporal rupture; all resolved with treatment.ConclusionsPotentially clinically meaningful and statistically significant improvements in penile curvature deformity and PD symptom bother scores were observed with intralesional injection of CCH compared with baseline in men with PD. CCH was generally well tolerated, with AEs primarily transient and local to injection site. In conjunction with previous studies, the results of this open‐label study support the use of CCH in the treatment of PD. Levine LA, Cuzin B, Mark S, Gelbard MK, Jones NA, Liu G, Kaufman GJ, Tursi JP, and Ralph DJ. Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie's disease: A phase 3 open‐label study. J Sex Med 2015;12:248–258.     

Safety of Collagenase Clostridium histolyticum Injection Therapy for Peyronie Disease in Patients Continuing Antiplatelet or Anticoagulant Therapy

IntroductionThe initial clinical trials for intralesional collagenase Clostridium histolyticum (CCh) injection therapy for Peyronie disease (PD) excluded men on antiplatelet or anticoagulant medications except those on low-dose aspirin. Men with PD who take such medications present a challenging clinical scenario because of a lack of evidence regarding the safety of CCh while on these drugs.AimTo evaluate safety outcomes among patients continuing anticoagulant and antiplatelet therapy during ongoing intralesional CCh injection treatment for PD.MethodsAn institutional review board approved a database of 187 patients treated with CCh at an academic men's health practice from January 2016 through April 2019 was reviewed. Men on antiplatelet/anticoagulant medications were not instructed to stop these agents. Data on patient demographics, comorbidities, CCh injection details, use or nonuse of antiplatelet/anticoagulant medications, and adverse events were extracted from the electronic medical record. Rates of hematoma formation, bruising, swelling, and corporal rupture were determined. Univariate statistical analysis compared clinical data and adverse events between men on or off antiplatelet/anticoagulant medications.Main Outcome MeasureStatistical comparison of adverse events in those taking or not taking antiplatelet or anticoagulant medications while undergoing intralesional CCh injection therapy for PD.ResultsOf 187 men undergoing CCh treatment, 33 (17.6%) were on concomitant antiplatelet or anticoagulant therapy. Aspirin 81 mg alone was the most common pharmacologic agent (58% of men on antiplatelet/anticoagulants); medications also included other antiplatelet drugs, warfarin, and novel oral anticoagulants (NOACs). Men taking blood thinners during intralesional CCh injection therapy experienced no statistical difference in rates of bruising, swelling, or hematoma formation compared with men not on antiplatelet/anticoagulants. No corporal ruptures were observed in either group. Men on antiplatelet or anticoagulant therapy were more likely to be older (64 vs 58 years old, P = 0.005), have hypertension (P = 0.025), and have hyperlipidemia (0.009).Clinical ImplicationsIntralesional CCh injection therapy may be offered to men on antiplatelet/anticoagulant medications without increased risk of adverse events.Strength & LimitationsThis study evaluated the experience of a single surgeon, with a systematic evaluation of adverse events captured in a robust electronic medical record. The retrospective nature of this study limits conclusions but builds upon work performed in the initial clinical trials for CCh.ConclusionOur findings suggest that antiplatelet and anticoagulant medications do not increase the risk of adverse events during intralesional CCh injection therapy for PD.Amighi A, Regets KV, Nork JJ, et al. Safety of Collagenase Clostridium histolyticum Injection Therapy for Peyronie Disease in Patients Continuing Antiplatelet or Anticoagulant Therapy. J Sex Med 2020;17:353–356.     

Characteristics of Men With Peyronie's Disease and Collagenase Clostridium Histolyticum Treatment Failure: Predictors of Surgical Intervention and Outcomes

BackgroundA subset of patients with Peyronie's disease (PD) treated with collagenase clostridium histolyticum (CCH) experience persistent bother and some require surgery.AimWe characterize patients experiencing persistent bother after CCH treatment and identify associations and predictors of surgical intervention/outcomes.MethodsWe 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.OutcomesThe primary outcome was surgery after CCH treatment. Secondary outcomes included worsened erectile function, sensory deficits, and penile length change.ResultsOf 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 ImplicationsPatients 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/LimitationsThis study's generalizability is limited by selection bias, but useful data are provided for patient counseling.ConclusionPatients 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;17:1005–1011.     

Continuing Collagenase Clostridium Histolyticum Injections Among Initial Nonresponders Results in Significant Curvature Improvements in the Majority of Peyronie's Disease Men

BackgroundIt 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.AimTo analyze curvature improvements from the final two series of CCH injections based on amount of improvement during the first 2 series.MethodsA 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.OutcomesThe 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.ResultsA 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.Clinical ImplicationsMen who fail to achieve significant benefits with 2 series of CCH injections may benefit from completing the final 2 series.Strengths and LimitationsStrengths including a relatively large, prospective series. Limitations include a single center, nonrandomization, nonblinded assessments, and restriction to men who completed eight injections.ConclusionsIn 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.Alom M, Burgon H, Ziegelmann M, et al. Continuing Collagenase Clostridium Histolyticum Injections Among Initial Nonresponders Results in Significant Curvature Improvements in the Majority of Peyronie's Disease Men. J Sex Med 2021;18:1092–1098.     

Efficacy of Combined Collagenase Clostridium histolyticum and RestoreX Penile Traction Therapy in Men with Peyronie’s Disease

BackgroundPrevious 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.AimTo 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.MethodsA 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).OutcomesChanges in penile length, curvature, and subjective perception and the occurrence of adverse events.ResultsOf 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 ImplicationsUse of the RestoreX device enhances mean curvature outcomes by 71% and increases penile length in men with PD receiving CCH therapy.Strengths & LimitationsStudy 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.ConclusionThe 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.     

Comparative Cost-effectiveness of Surgery,Collagenase Clostridium Histolyticum,and Penile Traction Therapy in Men with Peyronie’s Disease in an Era of Effective Clinical Treatment

BackgroundTraditionally, surgery has been considered the gold standard treatment for Peyronie’s disease (PD). Less-invasive alternatives, such as collagenase Clostridium histolyticum (CCH) and traction therapy, have been proposed and proven effective.AimTo compare cost-effectiveness of management options for PD.MethodsA Markov analytic model was created to compare the cost-effectiveness of treatment with a novel traction device, RestoreX (RXPTT), vs CCH vs surgery. Outcomes were derived from single-institution, prospective data of 63 men treated with RXPTT, 115 with CCH, and 23 with plication or incision and grafting. Costs were based on 2017 Medicare reimbursement and utility values from the literature.Main Outcome MeasuresModel outcomes included complications for each treatment arm, as well as the probability of success, which was defined as ≥20% improvement in curvature. Univariable and multivariable sensitivity analyses were performed to test the robustness of the model.ResultsOverall success rates were 96% (surgery), 66% (CCH), and 48% (RXPTT). At 10 years after treatment, RXPTT was the most cost-effective, with mean costs per patient of $883 (RXPTT), $11,419 (surgery), and $33,628 (CCH). CCH and surgery both resulted in a gain of quality adjusted life years (QALYs) relative to RXPTT (9.44 and 9.36 vs 9.27, respectively). Sensitivity analysis demonstrated greater cost-effectiveness for surgery if lower (≤46%) rates of postoperative erectile dysfunction or length loss (≤3%). CCH became more cost-effective at lower costs (≤$16,726) or higher success rates (≥76%). On multivariable sensitivity analysis at a willingness to pay threshold of $100,000/QALY, the most cost-effective strategy was RXPTT in 49%, surgery in 48%, and CCH in 3% of simulations. At a willingness to treat threshold of $150,000/QALY, the most cost-effective treatment option was RXPTT in 33%, surgery in 55%, and CCH in 12% of simulations.Clinical ImplicationsIn an era of value-based care, this model can guide cost-effective treatment selection on the basis of provider, patient, and payer characteristics.Strengths & LimitationsThe current study represents the first cost-effectiveness comparison of treatment modalities for PD and is strengthened by prospective data collection, large CCH and traction sample sizes, and robust sensitivity analyses. Consistent with cost-effective models, the model is limited by assumptions and may not apply to all scenarios.ConclusionsRXPTT represents a more cost-effective method for achieving ≥20% curvature improvement compared with surgery or CCH. Depending on treatment goals, rate of surgical complications, and willingness to pay threshold, surgery and CCH may become more cost-effective in select scenarios.Wymer K, Kohler T, Trost L. Comparative Cost-effectiveness of Surgery, Collagenase Clostridium Histolyticum, and Penile Traction Therapy in Men with Peyronie’s Disease in an Era of Effective Clinical Treatment. J Sex Med 2019;16:1421–1432.     

The Test–Retest Reliability of the Peyronie's Disease Questionnaire

IntroductionThe Peyronie's Disease Questionnaire (PDQ) is a disease-specific, patient-reported outcome instrument designed to measure the psychosexual consequences and treatment outcomes of Peyronie's disease (PD).AimThe aim of this study was to evaluate the test–retest reliability of the PDQ.MethodsAdult men with PD were recruited through eight clinical sites across the United States. Participants completed the PDQ during two study visits scheduled 7 (±3) days apart. At Visit 1, participants completed a sociodemographic questionnaire, the PDQ, and the International Index of Erectile Function (IIEF). At Visit 2, participants repeated the PDQ and completed an Overall Treatment Effect (OTE) scale. Test–retest reliability of the PDQ was assessed in a stable subsample (as determined by responses to the OTE). Intraclass correlation coefficients (ICCs) were calculated to evaluate the degree of association between the three PDQ subscale scores at Visits 1 and 2. Internal consistency of the subscales was also evaluated using Cronbach's alpha.Main Outcome MeasureThe main outcome measure was the PDQ.ResultsOf the 61 PD patients (mean age 59.3) who took part in the study, the majority were not receiving treatment for their PD (n = 35, 57.4%). The sample's mean score on the erectile function domain of IIEF was 19.7 (±8.2), indicating mild–moderate dysfunction. Nearly two-thirds reported penile pain at baseline (n = 37, 63.8%). Of the participants with baseline PDQ data and who had engaged in vaginal intercourse in the past 3 months, 57 completed both study visits. The PDQ demonstrated excellent test–retest reliability in 53 stable patients. The ICC was 0.85 for the Psychological and Physical Symptom subscale, 0.89 for the Peyronie's Symptom Bother subscale, and 0.88 for the Penile Pain subscale. The Cronbach's alpha estimates for all three subscales were acceptable at the >0.70 level.ConclusionsThe PDQ is a highly reproducible measure of PD and can be an effective end point in clinical trials evaluating treatments for PD. Coyne KS, Currie BM, Thompson CL, and Smith TM. The test–retest reliability of the Peyronie's Disease Questionnaire. J Sex Med 2015;12:543–548.     

ORIGINAL RESEARCH—PEYRONIE'S DISEASE: A Survey of Primary-Care Physicians and Urologists Regarding Peyronie's Disease

IntroductionPeyronie's disease (PD) is a connective tissue disorder with an uncertain etiology that causes penile deformity. The interest in PD and our understanding of the disorder has grown significantly in recent years. Data have shown that several previous beliefs regarding the prevalence, natural history, and treatment of PD were incorrect. The prevalence is significantly higher than the previously reported 1%, and most cases of PD do not spontaneously resolve.AimTo determine the extent to which newer information about PD has reached physicians who are likely to encounter men with PD and to determine practice patterns regarding this disorder.MethodsWe created a survey of 20 questions and mailed it to primary-care physicians (PCPs) and urologists (UROs) in Illinois and Wisconsin.Main Outcome MeasuresResponses to individual survey items were totaled.ResultsWe received 152 responses from PCPs and 98 from UROs for response rates of 43% and 44%, respectively. Survey results revealed the following: 63% of PCPs and 41% of UROs thought the prevalence is less than 1%; 17% of PCPs and 38% of UROs believed PD spontaneously resolves in greater than 50% of cases; 17% of PCPs and 9% of UROs did not think PD occurs in men younger than 40 years of age; 48% of PCPs and 37% of UROs did not believe that PD is frequently associated with ED; 51% of PCPs and 1% of UROs were unsure if any effective medical or surgical treatment for PD existed.ConclusionThese data suggest that many physicians who are very likely to encounter men with PD have incorrect assumptions about the disease, and this can negatively affect diagnosis and treatment of men with PD. LaRochelle JC, and Levine LA. A survey of primary-care physicians and urologists regarding Peyronie's disease.     

Low Testosterone Has a Similar Prevalence among Men with Sexual Dysfunction Due to Either Peyronie's Disease or Erectile Dysfunction and Does Not Correlate with Peyronie's Disease Severity

IntroductionLow testosterone (T) has been suggested as a risk factor for Peyronie's disease (PD) that may correlate with disease severity. Low T is common in men with sexual dysfunction but its role in the pathogenesis of PD remains unclear.AimThe aim of this study was to compare the prevalence of low T (<300 ng/dL) in patients presenting with PD or erectile dysfunction (ED), as well as disease severity between men with PD and either low T or normal T (≥300 ng/dL).MethodsRetrospective review of 300 men with either PD or ED was conducted. Men were excluded for combined PD and ED, psychogenic ED, or prior T use. For men with PD, plaque size, degree of curvature, and surgical correction rate were compared.Main Outcome MeasuresThe main outcome measures were (i) mean T levels in men with PD or ED and (ii) plaque size, degree of curvature, and surgical correction rates among men with PD and either low T or normal T.ResultsEighty‐seven men with PD and 98 men with ED were identified. Men with PD had mean total T and free T of 328 ng/dL and 11.5 ng/dL, while men with ED had mean levels of 332 ng/dL and 12.1 ng/dL, respectively (P > 0.05). Of PD men, 52.9% had low T, compared with 45.9% of men with ED (P = 0.35). T levels did not correlate with plaque size or degree of curvature in the PD group (P > 0.05).ConclusionsMen with sexual dysfunction characterized by either PD or ED had similarly low T levels, and low T did not correlate with PD severity or surgical correction rate. The comparable prevalence of low T in men with PD or ED suggests the high rate of low T in PD men may be related to a common process among men with abnormal erectile physiology and not specifically causative in plaque formation. Kirby EW, Verges D, Matthews J, Carson CC, and Coward RM. Low testosterone has a similar prevalence among men with sexual dysfunction due to either Peyronie's disease or erectile dysfunction and does not correlate with Peyronie's disease severity. J Sex Med 2015;12:690–696.     

Standard Operating Procedures for Peyronie's Disease

IntroductionPeyronie's disease (PD) refers to a penile deformity that is associated with sexual dysfunction.AimTo provide recommendations and Standard Operating Procedures (SOPs) based on best evidence for diagnosis and treatment of PD.MethodsMedical literature was reviewed and combined with expert opinion of the authors.Main Outcome MeasuresRecommendations and SOPs based on grading of evidence–based medical literature.ResultsPD is a fibrotic wound-healing disorder involving the tunica albuginea of the corpora cavernosa. The resulting scar is responsible for a variety of deformities, including curvature, shortening, narrowing with hinge effect, and is frequently associated in the early phase with pain. Patients frequently experience diminished quality erections. All of these conditions can compromise sexual function for the affected male. The etiopathophysiology of PD has yet to be clarified and as a result, effective, reliable, mechanistic directed non-surgical therapy is lacking.ConclusionsThe management of PD consists of proper diagnosis and treatment, ranging from non-surgical to surgical interventions. The main state of treatment for PD rests at this time on surgical correction that should be based on clear indications, involve surgical consent, and follow a surgical algorithm that includes tunica plication, plaque incision/partial excision and grafting, and penile prosthesis implantation. Levine LA and Burnett AL. Standard operating procedures for Peyronie's disease. J Sex Med 2013;10:230-244.     

Peyronie's Disease among Men Who Have Sex with Men: Characteristics,Treatment, and Psychosocial Factors

IntroductionWe describe the characteristics of Peyronie's disease (PD) and its associated psychosocial implications in men who have sex with men (MSM).AimThe aims of this article are to identify presenting characteristics and treatment for MSM with PD, compare these findings to non‐MSM PD patients, and determine the psychosocial impact of PD among MSM.Main Outcome MeasuresSubjective and objective presenting characteristics, MSM psychosocial factors.MethodsWe identified 27 MSM with PD presenting from 2000 to 2012 through a retrospective chart review. A random selection of 200 non‐MSM PD patients was identified, who presented during the same time period. A prospective nonvalidated questionnaire was given to MSM PD patients for evaluation of psychosocial constructs.ResultsA traumatic event leading to activation of PD was identified equally among MSM and non‐MSM (P = 0.815). Most common recognized activators of PD among MSM were: penetrative sexual intercourse (22.2%), self‐stimulation (11.1%). More MSM presented with the primary complaint of penile deformity, including narrowing, indentation, hourglass, and hinge (11.1% MSM vs. 1.0% non‐MSM, P = 0.01). No differences in total curvature, erection grade were found (P > 0.05). PD had a negative effect on emotional status (89.0% MSM, 80.5% non‐MSM, P > 0.05) and intimate relationships (45.0% MSM, 64.0% non‐MSM, P > 0.05). Nonsurgical treatment was given to 88.9% MSM and 76.5% non‐MSM (P > 0.05), and corrective surgery in 29.6% MSM and 25.0% non‐MSM (P > 0.05). Of the 75.0% of MSM engaging in anal sex, 41.7% reported penetrative anal intercourse as the activator of PD. Among MSM, 31.3% experienced decreased libido, 50.0% decreased frequency of sexual activity, 92.9% were self‐conscious about the appearance of their penis, and 92.9% were dissatisfied with the size of their penis.ConclusionsFew differences exist in the clinical presentation and treatments used between MSM and non‐MSM PD patients. There was evidence of emotional distress in both groups. As a result, psychosexual assessment and treatment, when indicated, should be considered essential to the patient presenting with PD. Farrell MR, Corder CJ, and Levine LA. Peyronie's disease among men who have sex with men: Characteristics, treatment, and psychosocial factors. J Sex Med 2013;10:2077–2083.     

Comparing and Contrasting Peyronie's Disease Guidelines: Points of Consensus and Deviation

BackgroundPeyronie’s disease (PD) is a challenging clinical entity. To assist clinicians with diagnosis and management, four separate organizations have published PD guidelines over the past five years, but there remains a lack of consensus and data-driven recommendations for many aspects of diagnosis and treatment.AimTo compare and contrast PD guidelines, highlighting key similarities and differences among the guideline panel recommendations and identify areas for further research.MethodsWe performed an extensive review to compare and contrast diagnosis and treatment recommendations from publically available published PD guidelines from four different organizations: American Urological Association, European Association of Urology, Canadian Urologic Association, and the International Society of Sexual Medicine.OutcomesKey similarities and differences with regards to definition, evaluation, nonsurgical and surgical treatments were compared.ResultsPoints of general consensus among the guideline panels included: History is adequate for diagnosis of PD, and intracavernosal injection is a gold standard to evaluate penile deformity prior to invasive intervention. Careful counseling with shared decision-making is required prior to treatment. In general, plication and incision and/or grafting surgery is reserved for patients with preserved erectile function whereas penile prosthesis implantation is the only surgical option for PD patients with erectile dysfunction. Overall, nonsurgical treatments have inferior evidence of efficacy with these being the main area of controversy; however, all societies recognize that intralesional injections may be used. 0Further research into the pathophysiology of PD may direct novel treatments targeted towards early intervention and rigorous outcomes research may direct best practices for the surgical treatment of PD in the future.Clinical ImplicationsPD is a challenging clinical entity. Direct comparison of the published PD guidelines highlights clear standards of care as well as areas where more research is needed to promote higher levels of evidence-based practice.Strengths & LimitationsTo our knowledge this is the first report to directly compare and contrast published guidelines pertaining to the diagnosis and management of PD. Limitations include the lack of evidence-quality review pertaining to individual guideline recommendations, although this was not the aim of this review.ConclusionWe highlight consensus of major urologic societies on many aspects of work up and management of PD with notable exceptions which may guide further research.Manka MG, White LA, Yafi FA, et al. Comparing and Contrasting Peyronie's Disease Guidelines: Points of Consensus and Deviation. J Sex Med 2021;18:363–375.