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.     

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.     

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.     

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.     

Collagenase Clostridium histolyticum for the Treatment of Peyronie's Disease: The Development of This Novel Pharmacologic Approach

IntroductionThe conception of collagenase Clostridium histolyticum (CCH) as treatment for Peyronie's disease (PD) was a vital first step in providing a nonsurgical, minimally invasive FDA-approved treatment for men with PD.AimTo review the origins, clinical research history, and ultimately FDA approval of collagenase as PD treatment.MethodsA PubMed search using (Peyronie's or Peyronie) AND collagenase, and limited to clinical research studies, returned nine papers that were examined in the current review.ResultsCollagenase as a PD treatment arose in response to a lack of effective nonsurgical treatments and the incomplete understanding of underlying PD etiology. Awareness of dense collagen in PD scarring and parallel initial exploration of collagenase to treat herniated lumbar discs coincided with and inspired laboratory-based investigation of collagenase effects on excised PD plaque tissue. The foundational conceptual work and the critical development of purified injectable collagenase allowed the pursuit of clinical studies. Progression of clinical studies into large-scale robust trials culminated in two important outcomes: development of the first validated, PD-specific measure of psychosexual function, the Peyronie's Disease Questionnaire, and the first FDA-approved treatment for PD.ConclusionsCollagenase therapy began as an attempt to modify the structure of PD-related tunica albuginea scarring, despite the lack of a fundamental understanding of the scar's origin. If we wish to advance PD treatment beyond this first effective step, the future needs to bring us full circle to the starting point: We need a greater understanding of the control of collagen deposition and wound healing in men with PD. Gelbard MK, Chagan L, and Tursi JP. Collagenase Clostridium histolyticum for the treatment of Peyronie's disease: The development of this novel pharmacologic approach. J Sex Med 2015;12:1481–1489.     

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.     

Correlation of Degree of Penile Curvature between Patient Estimates and Objective Measures among Men with Peyronie's Disease

IntroductionAmong men with Peyronie's disease (PD), the degree of penile curvature has significant implications on psychological well-being, sexual function, treatment planning, and posttherapy evaluations.AimThe primary objective of the current study was to correlate patients' estimates of penile angulation with objective measures.Main Outcome Measures(i) Proportion of patients over- or underestimating their actual degree of curvature; and (ii) degree differences between patient estimates and objective measures of penile curvature.MethodsAt baseline, patients with established PD were asked to provide a “best estimate” of their degree of penile curvature. Objective measures of penile angulation were then performed using standardized photographs and protractor-based measurement of penile curvature during full erection. Correlations were performed between patient estimates of penile curvature and objective measures of penile angulation.ResultsEighty-one men with established PD and a mean age of 52 years (range: 20–72 years) were prospectively evaluated. Mean duration of disease was 33 months (range: 6–276 months), and mean plaque size was 1.4 cm ± 0.1 standardized error (SE). The proportion of patients with dorsal, lateral, and ventral curvatures was 39%, 57%, and 4%, respectively. Patient estimates of baseline penile curvature (mean 51 degrees ± 3.1 SE) differed significantly from objective measurements (mean 40 degrees ± 2.4, P = 0.001). A significantly higher proportion of patients overestimate their actual degree of penile curvature (54% overestimate, 26% underestimate, and 20% are accurate within 5 degrees, P = 0.002). Compared with objective measures, patients' estimates of degree of penile curvature differed by an average of 20 degrees ± 2.2 SE.ConclusionsPatients with PD tend to overestimate their degree of penile curvature. Objective measurement of penile angulation is necessary to accurately counsel patients regarding disease severity, recommend appropriate treatment strategies, and objectively evaluate outcomes following therapy. Bacal V, Rumohr J, Sturm R, Lipshultz LI, Schumacher M, and Grober ED. Correlation of degree of penile curvature between patient estimates and objective measures among men with Peyronie's disease. J Sex Med 2009;6:862–865.     

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.     

Predictors of Depression in Men With Peyronie's Disease Seeking Evaluation

BackgroundPeyronie's disease (PD) has negative impacts on the psychosocial status of men including depression warranting clinical evaluation in up to 50% of men.AimTo examine predictors of depression in patients with early PD seeking evaluation.MethodsAll PD patients at a high-volume PD practice underwent screening and curvature assessment after intracavernosal injection. Complex deformity was defined as any degree of multiplanar curvature, curvature >60 degrees, or presence of hourglass deformity. Men completed the PD questionnaire (PDQ), a validated depression questionnaire (CES-D) as well as the Self-Esteem and Relationship (SEAR) questionnaire. Scores of ≥16 on CES-D were considered indicative of moderate/severe depression. Predictors of the presence of depression were defined using univariable and multivariable logistic regression.OutcomesDemographic, bother and curve related predictors of depression in men with PD.Results408 men completed all questionnaires. Mean age was similar between depressed and nondepressed groups (57 ± 10 years overall, P = .60 between groups). Proportions of erectile dysfunction were similar between groups (P = .96). Mean PD duration was similar between groups (19 ± 35 months overall, P = .46 between groups). Mean degree of curvature was 38 ± 2 degrees in the depressed vs 33 ± 1 degrees in the nondepressed groups (P = .03). A complex deformity was seen in 64.5% in the depressed vs 61.5% in the nondepressed (P = .56). A total of 110 (27%) patients had CESD scores ≥16. 74% depressed men were in relationships compared to 84% nondepressed men (P < .01). Other characteristics including bother, pain, duration of disease, curve complexity and instability were similar between the two groups. On univariable analysis, factors protective against depression included being partnered (OR 0.42, 95%CI 0.24–0.75, P < .01) and higher total SEAR scores (OR 0.95, 95%CI 0.94–0.97, P < .01). Elevated PDQ domain scores were associated with depression (Psychologic Symptoms 1.05, 95%CI 1.02–1.10, P < .01; Pain 1.08, 95%CI 1.03–1.12, P < .01; Bother 1.11, 95% CI 1.05–1.68, P < .01) as well as baseline history of depression (OR 2.93, 95%CI 1.67–5.14, P < .001). On multivariable analysis, only total SEAR score remained protective against depression (OR 0.96, 95%CI 0.94–0.97, P < .001).Clinical ImplicationsProviders must recognize that men with PD seeking evaluation have meaningful rates of depression for which early recognition is necessary.Strengths and LimitationsRetrospective review of a large prospectively collected dataset from a single center of men with PD utilizing a validated screening tool for depression.ConclusionWhile no significant demographic, bother or curve related factors predicted depression in early PD men seeking evaluation, it remains a significant problem warranting further prospective evaluation.P. Nahid, N. Bruno, S. Carolyn, et al. Predictors of Depression in Men With Peyronie's Disease Seeking Evaluation. J Sex Med 2021;18:783–788.     

Predictive Factors of Patients' and Their Partners' Sexual Function Improvement After Collagenase Clostridium Histolyticum Injection for Peyronie's Disease: Results From a Multi-Center Single-Arm Study

Background

Collagenase Clostridium histolyticum (CCH; Xiapex) injections represent the only licensed medical treatment for Peyronie's disease (PD).

Concordance Between Patient and Physician Assessment of the Magnitude of Peyronie's Disease Curvature

IntroductionThe magnitude of penile deformity is a critically important factor in Peyronie's disease, as it is associated with increased difficulty in penetrative sexual intercourse and in turn with negative psychosocial consequences. Deformity magnitude also influences treatment choice when surgical correction is indicated.AimTo determine the concordance between patient and physician assessment of magnitude of penile curvature in men with Peyronie's disease.MethodsPatient assessment of curvature was obtained at initial interview. Physician assessment was performed using intracavernosal injection-assisted erection using a goniometer applied during excellent penile rigidity.Main Outcome MeasuresPatient and physician assessments of penile curvature.ResultsThe sample consisted of 192 men with a mean age of 54 ± 12 years old. Mean curvature on patient and physician assessment was 33 ± 17 and 36 ± 18 degrees, respectively. Only 49% of patients (94) correctly assessed their curvature, whereas 35% underestimated and 16% overestimated it.ConclusionsOnly half of PD patients accurately assess their penile curvature, with more than twice as many patients underestimating it than overestimating it. These data suggest that patient self-reporting of penile curvature should not be used as a clinical marker or end point in Peyronie's disease trials. Matsushita K, Stember DS, Nelson CJ, and Mulhall JP. Concordance between patient and physician assessment of the magnitude of Peyronie's disease curvature. J Sex Med 2014;11:205–210.     

Evaluating the Impact of Penile Girth Discrepancy on Patient Bother in Men With Peyronie's Disease: An Observational Study

BackgroundMen with Peyronie's disease (PD) may experience penile narrowing. Little data on penile girth changes and their psychosocial impact exist.AimTo assess girth discrepancy in men with PD and its association with patient bother.MethodsThis was a retrospective observational study. All patients with PD at our institution who were seen in the sexual medicine clinic and who completed 3 validated instruments the PD questionnaire (PDQ), Self-Esteem and Relationship (SEAR) questionnaire, and a depression questionnaire, the Center for Epidemiologic Studies Depression Scale (CES-D), and a curvature assessment were included. Patient and PD characteristics are described. Associations of instability and bother to girth differences are assessed. 2 outcomes for girth differences are classified as (i) girth difference of ≥ 1 cm vs less and (ii) girth differences of ≥10% vs less. Unadjusted and adjusted effects of PD and patient characteristics are assessed on the outcome of high bother using logistic regression models.OutcomesThe main outcomes of this study were penile girth changes, instability, and questionnaire scores. High bother was defined as a PDQ bother score of ≥9.ResultsA total of131 men had midshaft curvature and were the focus of the study. Their mean age was 59 ± 9 (range 31–78) years. PD duration was 16 ± 25 (range 1–180) months, with a mean degree of primary curvature of 37 ± 20^o. Mean girth difference between base and point of maximum curvature was 0.78 ± 0.53 cm equating to a mean girth difference at point of maximum curvature of 6 ± 4%. Instability was present in 53% of men. There were 54 men with a girth difference of ≥ 1 cm and 23 men with a ≥10% change in girth. There was no difference in CES-D, SEAR, or PDQ domain scores or high bother in men with significant girth changes. Univariable analysis of predictors of high bother included the degree of curvature (odds ratio [OR]: 1.06; P < .001), instability (OR 6.62; P < .001), CES-D sum (OR 1.09; P = .002), and SEAR score (OR 0.96; P = .001). On multivariate analysis, only the degree of primary curvature was predictive of high bother (OR 1.06; P < .001).Clinical ImplicationsPenile girth changes have little impact on overall psychosocial well-being. The degree of penile curvature is the primary predictor of patient bother.Strengths and LimitationsStrengths include a large patient population and use of validated questionnaires. Limitations include single-center, retrospective study and subjective instability grading.ConclusionsPenile girth discrepancy in men with PD has limited psychosocial impact. Clinically significant bother was associated with the degree of primary curvature.Salter CA, Nascimento B, Terrier, JE, et al. Evaluating the Impact of Penile Girth Discrepancy on Patient Bother in Men With Peyronie's Disease: An Observational Study. J Sex Med 2020;17:1560–1565.     

ORIGINAL RESEARCH—PEYRONIE'S DISEASE: Use of Penile Extender Device in the Treatment of Penile Curvature as a Result of Peyronie's Disease. Results of a Phase II Prospective Study

IntroductionPilot experiences have suggested that tension forces exerted by a penile extender may reduce penile curvature as a result of Peyronie's disease.AimTo test this hypothesis in a Phase II study using a commonly marketed brand of penile extender.MethodsPeyronie's disease patients with a curvature not exceeding 50° with mild or no erectile dysfunction (ED) were eligible. Fifteen patients were required to test the efficacy of the device assuming an effect size of >0.8, consistent with an “important” reduction in penile curvature. Changes in penile length over baseline and erectile function (EF) domain scores of the International Index of Erectile Function (IIEF) constituted secondary end points.Main Outcome MeasuresPatients were counselled on the use of the penile extender for at least 5 hours per day for 6 months. Photographic pictures of the erect penis and measurements were carried out at baseline, at 1, 3, 6, and 12 months (end of study). The IIEF-EF domain scores were administered at baseline and at the end of study. Treatment satisfaction was assessed at end of study using a nonvalidated institutional 5-item questionnaire.ResultsPenile curvature decreased from an average of 31° to 27° at 6 months without reaching the effect size (P = 0.056). Mean stretched and flaccid penile length increased by 1.3 and 0.83 cm, respectively at 6 months. Results were maintained at 12 months. Overall treatment results were subjectively scored as acceptable in spite of curvature improvements, which varied from “no change” to “mild improvement.”ConclusionsIn our study, the use of a penile extender device provided only minimal improvements in penile curvature but a reasonable level of patient satisfaction, probably attributable to increased penile length. The selection of patients with a stabilized disease, a penile curvature not exceeding 50°, and no severe ED may have led to outcomes underestimating the potential efficacy of the treatment. Gontero P, Di Marco M, Giubilei G, Bartoletti R, Pappagallo G, Tizzani A, and Mondaini N. Use of penile extender device in the treatment of penile curvature as a result of Peyronie's disease. Results of a phase II prospective study. J Sex Med 2009;6:558–566.     

The Prevalence of Peyronie's Disease in Japan: A Study in Men Undergoing Maintenance Hemodialysis and Routine Health Checks

IntroductionThe incidence of Peyronie's disease (PD) in the general population is believed to be as high as 20%. However, most of the data concerning the prevalence of PD have been obtained from Caucasian populations.AimThe aim of this study was to examine the prevalence of PD in Asia and among men undergoing hemodialysis and discuss the pathophysiology of PD.MethodsA total of 1,090 men who received a routine health check at our hospital (control group) as well as 130 male patients undergoing maintenance hemodialysis were enrolled. The diagnosis of PD was based on a palpable penile plaque.Main Outcome MeasuresHemodialysis patients were asked about their sexual activity and completed the International Index of Erectile Function‐5 questionnaires. The differences between patients' and hemodialysis‐associated factors, comorbidities, and medications were statistically assessed for patients with and without PD.ResultsThe prevalence of PD was significantly increased among hemodialysis patients (12 patients: 9.2%) relative the control group (six men: 0.6%) (P < 0.0001, odds ratio: 18.4). In both groups, the plaques were primarily allocated dorsally. In the hemodialysis patients with PD, the frequency of masturbation (P < 0.05) and the incidence of moderate or severe erectile dysfunction (P < 0.01) were significantly higher than those among hemodialysis patients without PD. In comparison with patients without PD, the number of acetate dialysate users was significantly higher among patients with PD (P < 0.05), and none of the PD patients used angiotensin‐related antihypertensive drugs (P < 0.05).ConclusionsThe prevalence of PD in healthy Japanese men is low (0.6%), which suggests the existence of racial differences in the prevalence of PD. Moreover, these results indicate that hemodialysis increases the incidence of PD. The differences in the characteristics between male hemodialysis patients with and without PD provide new insights into the pathophysiology and therapeutic window of PD. Shiraishi K, Shimabukuro T, and Matsuyama H. The prevalence of Peyronie's disease in Japan: A study in men undergoing maintenance hemodialysis and routine health checks. J Sex Med **;**:**–**.     

Extracorporeal Shock Wave Therapy in Peyronie's Disease: Results of a Placebo-Controlled,Prospective, Randomized,Single-Blind Study

IntroductionExtracorporeal shock wave therapy (ESWT) for treatment of Peyronie's disease (PD) is controversial.AimTo study the efficacy of ESWT by a placebo-controlled, randomized trial.MethodsPatients with PD (n = 102) were randomly assigned (n = 51) to each group (ESWT or placebo). All patients were given 6 weekly treatments. Patients in the ESWT-group received 2,000 shock waves per session, using the Piezoson 100 lithotripter (Richard Wolf, Knittlingen, Germany). Patients in the placebo-group were treated with interposition of a plastic membrane, which prevented any transmission of shock waves.Main Outcome MeasuresPrimary end point was decrease of pain between baseline and after 4 weeks follow-up. Secondary end points were changes in deviation, plaque size, and sexual function. Pain was assessed by a visual analog scale. Deviation was measured by a goniometer after artificial erection using Alprostadil (Viridal^®, Schwarz Pharma, Monheim, Germany). Plaque size was measured with a ruler and sexual function assessed by a scale regarding the ability to perform sexual intercourse.ResultsOverall, only 45 patients experienced pain at baseline. In the subgroup analysis of these patients, pain decreased in 17/20 (85.0%) patients in the ESWT group and 12/25 (48.0%) patients in the placebo group (P = 0.013, relative risk [RR] = 0.29, 95% confidence interval: 0.09–0.87). Penile deviation was not reduced by ESWT (P = 0.66) but worsened in 20/50 (40%) and 12/49 (24.5%) patients of the ESWT and placebo-group, respectively (P = 0.133). Plaque size reduction was not different between the two groups (P = 0.33). Additional, plaque size increased in five patients (10.9%) of the ESWT group only. An improvement in sexual function could not be verified (P = 0.126, RR = 0.46).ConclusionsDespite some potential benefit of ESWT in regard to pain reduction, it should be emphasized that pain usually resolves spontaneously with time. Given this and the fact that deviation may worsen with ESWT, this treatment cannot be recommended. Hatzichristodoulou G, Meisner C, Gschwend JE, Stenzl A, and Lahme S. Extracorporeal shock wave therapy in Peyronie's disease: Results of a placebo-controlled, prospective, randomized, single-blind study. J Sex Med 2013;10:2815–2821.     

Multicenter Experience Using Collagen Fleece for Plaque Incision With Grafting to Correct Residual Curvature at the Time of Inflatable Penile Prosthesis Placement in Patients With Peyronie's Disease

BackgroundAdjuvant maneuvers are often necessary to correct residual curvature during inflatable penile prosthesis (IPP) placement in patients with Peyronie's disease (PD).AimWe present our multicenter experience using collagen fleece as graft material for plaque incision and grafting (PIG) during IPP placement in patients with moderate to severe PD.MethodsWe retrospectively reviewed 51 patients with IPP from 3 sites who underwent PIG with Tachosil (Baxter, IL) collagen fleece. Coloplast (Minneapolis, MN) IPP devices were used. Factors associated with residual curvature, revision, and patient satisfaction were performed using chi-squared analysis.OutcomesWe evaluated postoperative outcomes including factors associated with residual curvature, revision, and patient satisfaction.ResultsThe mean compound curvature was 69.6°. The mean follow-up was 10.6 (range 1–38) months. All patients reported erections sufficient for penetrative intercourse at the last follow-up. Residual curvature <15° was noted in 6 of 51 (12%) patients. 3 patients required device revision. 2 patients experienced temporary glanular paresthesia, and no patients experienced device infection.Clinical ImplicationsIn our multicenter study, patients experienced substantial curve correction with minimal complications, and in the few patients who had persistent mild curvature, severe preoperative curvature (>60°) was found to be the only risk factor.Strengths & LimitationsOur study represents the largest series of patients coming from multiple centers undergoing surgical correction of PD with IPP and collagen fleece grafting. Limitations of this study include the retrospective study design, lack of a comparison group, and modest follow-up.ConclusionPIG using collagen fleece is a safe and effective means of correcting residual curvature after IPP placement in patients with moderate to severe PD.Hatzichristodoulou G, Yang DY, Ring JD, et al. Multicenter Experience Using Collagen Fleece for Plaque Incision With Grafting to Correct Residual Curvature at the Time of Inflatable Penile Prosthesis Placement in Patients With Peyronie's Disease. J Sex Med 2020;17:1168–1174.     

A Critical Analysis of Reporting in Systematic Reviews and Meta-Analyses in the Peyronie's Disease Literature

BackgroundDespite an increasing number of publications on Peyronie's disease (PD), evidence-based clinical decision-making remains challenging due to the small number of well-designed clinical trials.AimTo perform a critical analysis of reporting quality in PD systematic reviews (SR) and meta-analyses (MA).MethodsStudy protocol registration was performed on the Open Science Framework platform. In January 2021, a systematic electronic search of the Medline/PubMed, Embase, Ovid, Scopus, Joanne Briggs Institute, and Cochrane databases was performed. Search terms included “Peyronie's disease” and “systematic review OR meta-analysis OR meta-analysis.” Eligibility criteria were English-language, relevance to PD and specification of “systematic review” or “meta-analysis” in the title or abstract. Oxford Center for Evidence-Based Medicine levels of evidence were used to classify original studies reviewed within each publication. Risk of bias was assessed using the ROBIS tool. Data were tabulated and reported as means with standard deviation, median with interquartile range and t-testing as appropriate. Strength of association between variables was calculated using Pearson correlation coefficient. Statistical analyses were performed on RStudio (version 1.4.1106).OutcomesOutcomes included review type, level of evidence, authorship, journal, publication date, “A MeaSurement Tool to Assess systematic Reviews” (AMSTAR-2) score and “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) score.ResultsFrom 1974 to 2021, 340 articles were identified. After review, 17 full length articles were included. Thirteen were SR, 2 MA and 2 was combined. Significant heterogeneity was seen in evidence level of included studies. There was median 54% adherence to AMSTAR-2 criteria and 74% adherence to PRISMA criteria. Overall AMSTAR-2 confidence rating was Critically Low in 11 of 17 studies. Correlation analysis revealed very high positive association between AMSTAR 2 and PRISMA adherence (+0.95). ROBIS revealed “High” concern regarding methods used to collect data and appraise 12/17 studies (71%), and “High” concern regarding synthesis and findings in 8 of 17 studies (47%).Clinical ImplicationsMany SR include markedly heterogenous levels of evidence and fail to meet accepted methodological criteria for reporting.Strengths and LimitationsMain strengths include extensive literature review and analysis of standardized study reporting. One limitation is that aggregate scoring of AMSTAR-2 and PRISMA is not intended as primary method of quality assessment; however effect was minimized by reporting critical domains, overall quality assessments and specifics on globally poorly reported domains.ConclusionMore high quality randomized controlled PD trials are necessary; SR and MA should focus on these studies alone.Bole R, Gottlich HC, Ziegelmann MJ, et al. A Critical Analysis of Reporting in Systematic Reviews and Meta-Analyses in the Peyronie's Disease Literature. J Sex Med 2022;19:629–640.