Diagnosis and management of Peyronie s disease: an evidence-based review

Transcription

1 18 Diagnosis and management of Peyronie s disease: an evidence-based review ERIC CHUNG Peyronie s disease presents a considerable therapeutic dilemma because of an incomplete understanding of the pathophysiology of the condition and the relative paucity of level 1 evidence studies. Eric Chung discusses how the growing volumes of literature should allow the clinician to educate and counsel patients on the many treatment options available. Figure 1. Peyronie s disease Eric Chung, MB BS, FRACS(Urol), Associate Professor of Surgery, Consultant Urological Surgeon, University of Queensland, Princess Alexandra Hospital; St Andrew s Pelvic Medicine Centre, St Andrew s War Memorial Hospital, Brisbane, Queensland, Australia Peyronie s disease (PD) is a debilitating sexual condition characterised by penile pain, curvature and/or (Figure 1), palpable plaque and erectile dysfunction (ED). 1 While no one truly knows the underlying pathophysiology of PD, it is generally agreed that it is considered an aberrant wound-healing disorder and that the development of PD is a result of repetitive trauma to the erect penis with ensuing fibrous plaque formation within the bilayer of tunica albuginae among genetically susceptible individuals. 1 Studies have shown that PD occurs in up to 9% of adult men and it is often difficult to predict the natural history, with up to 48% of cases progressing if left untreated. 2 PD often results in increased risk of depression, low self-esteem and relationship difficulties, and affects both the man s and his partner s quality of life. 1,3 The PD process can be divided into two main phases: acute (inflammatory) and chronic (stable) stages. In the acute stage, the patient usually describes a short duration (less than 6 months), penile pain, or changing penile curvature and/or. 4 The chronic phase of PD is characterised by the presence of penile plaque, a complex such as hinge or hourglass and ED. The majority of penile plaque occurs on the dorsal aspect, giving rise to dorsal penile curvature, 5 and in advanced cases the plaque can become ossified causing considerable penile shortening. 1 DIAGNOSIS OF PD The diagnosis of PD is usually evident on clinical history, penile examination and digital photographs. The history should specifically address time of onset, pain,, palpable penile lesion, preceding trauma, previous therapy and presence of ED. The presence of ED is not uncommon among men with PD. At present, a PD questionnaire is not used commonly outside of research even though it has been validated. 6 The assessment of ED can be made using the validated International Index of Erectile Function-5 questionnaire. 3 Questions regarding sexual dysfunction

2 19 such as loss of penile length, ejaculation, orgasm and change in sensation are often useful. On examination, the penis should be stretched fully to assess the penile length and to palpate underlying penile plaque. Digital photographs and penile examination with the aid of vasoactive intracavernosal injection are useful to document the extent of PD, vascular integrity and erectile response. The use of penile duplex ultrasonography often aids the diagnosis and provides additional prognostic information. 7 Patients with isolated septal scar often complain of loss of penile length, while those with intracavernosal fibrosis have difficulty maintaining an erection. Furthermore, larger plaque size and impaired cavernosal arterial flow diagnosed on penile colour duplex scan correlate strongly with ED. 8 TREATMENT OF PD Among the greatest challenges facing clinicians treating patients with PD is the lack of a defined treatment protocol and rehabilitative strategies, and often the treatment pathways are dictated based on physician intuition. 1 Increasing knowledge concerning the molecular basis of PD is evolving as a result of important new innovative basic science research studies, 9 and growing volumes of literature on various therapeutic options in PD have now allowed clinicians to educate and counsel patients on various treatment options (Figure 2 and Table 1). 1 The current therapy for PD can be divided into three groups: namely, medical therapy, minimally invasive therapy and surgery. Patients should be counselled on the benefits and risks of each individual treatment. MEDICAL THERAPY Oral therapies Medical or non-surgical management of PD is usually offered in men with early phase of PD, ie men with unstable or progressive penile curvature and painful erection, as well as those not psychologically ready or interested in Men with PD Acute phase of PD Penile pain Duration <6 months Chronic phase of PD No penile pain Duration 6 months Complex curvature Medical therapy Surgical interventions Minimal palpable plaque No plaque ossification Palpable penile plaque Mild/moderate plaque ossification Curvature <60 degrees No hourglass Good erectile function Penile plication surgery A. Oral agents B. Topical therapies A. Intralesional injectables B. Topical therapies Curvature >60 degrees Hourglass Good erectile function Penile graft surgery Poor erectile function Medical refractory ED Penile prosthesis Figure 2. Diagnosis and management of Peyronie s disease (PD) TRENDS IN UROLOGY & MEN S HEALTH JANUARY/FEBRUARY

3 20 Treatment agents Indications Advantages Disadvantages Oral agents Penile pain Simple Effective in less than 40% of cases PDE5 inhibitors Duration <6 months May treat ED Ineffective in complex pentoxifylline Intralesional injections Palpable plaque Minimally invasive Treatment schedule up to 4 6 weeks verapamil Duration <6 months May treat ED Effective in less than 40% of cases interferon 2 beta Penile pain Ineffective in complex collagenase Iontophoresis Penile pain Simple Effective in less than 40% of cases Duration <6 months May treat ED Ineffective in complex Low-intensity shockwave therapy Penile pain Simple Treatment schedule up to 4 6 weeks Duration <6 months May treat ED Effective in less than 40% of cases Ineffective in complex Penile traction therapy Penile pain Minimally invasive Long treatment schedule (3 6 months) Duration <6 months Effective in less than 40% of cases Ineffective in hourglass Device application can be difficult Penile plication Duration 6 months Minimally invasive Penile length loss Stable curvature <60 operation Decreased sensation Normal erection Lower risk of ED May worsen hourglass Persistent/recurrent curvature Penile graft surgery Duration 6 months More invasive Risk of ED Stable curvature 60 operation Decreased sensation Complex penile curvature May preserve penile Recurrent curvature Normal erection length Address hourglass Penile prosthesis implant with PD and ED More invasive Mechanical and non-mechanical adjunctive manoeuvres Medically refractory ED operation complications May preserve penile length Address hourglass PDE5, phosphodiesterase type 5; ED, erectile dysfunction. Table 1. Indications, advantages and disadvantages of various treatment options in Peyronie s disease (PD)

4 21 surgical intervention. The efficacy of oral therapy in PD is questionable and published literature is often restricted to a small number of patients in various PD phases and with limited objective outcome measures. Several randomised studies have shown that oral vitamin E, colchicine, carnitine, potassium aminobenzoate and tamoxifen are largely ineffective. 1 More recent studies have highlighted the potential beneficial role of pentoxifylline 10 and low-dose tadalafil 11 in PD. Intralesional injectables Intralesional injections are suitable in younger men with acute phase of ED, small clinical palpable, non-ossified plaque disease and mild/moderate penile curvature. 12 Of the injectable agents in PD, verapamil, interferon alpha 2B and collagenase are shown to be effective in placebo-controlled trials. The disadvantages to intralesional injections are penile pain and bruise, the need for a repetitive treatment cycle, and efficacy of less than 50%. 13 More recently it has been reported that combination therapies using oral therapy, intralesional injections and penile traction therapy may have additional benefits compared with single therapy. 14 Topical therapies The use of low-intensity shockwave therapy has been explored in the past and recent advances in this technology have stimulated renewed interest. Unfortunately, published literature on the efficacy of lowintensity shockwave therapy on PD-related has not been strong. 1 Iontophoresis or transdermal electromotive administration of dexamethasone, verapamil and lidocaine may be effective in terms of reduction of pain, plaque size and curvature, but further studies are required to evaluate fully the role of iontophoresis as a treatment modality in PD. 1 The role of penile traction therapy in PD has gained considerable interest lately and current published literature suggests that traction therapy is effective in increasing penile length and reducing the penile as well as possibly penile pain. 15 The ideal candidate is a patient with acutephase PD and short penis, large penile curvature with no calcified penile plaque or complex penile and normal erectile function. However, the patient needs to be highly motivated and compliant with use of a traction device for a minimum of 4 6 hours per day for at least 3 6 months in order to gain maximal benefit. SURGICAL INTERVENTIONS Surgery is indicated in men who have failed conservative measures and/or have stable PD (ie history longer than 6 months with no pain and stable ). In addition, patients who have extensive plaque calcification and those who want the quickest and most reliable outcome should consider surgery. 16 It is important to provide adequate preoperative counselling to set the patient s expectation, as surgery is associated with the risks of loss of penile length, persistent or recurrent curvature, ED and altered penile sensation postoperatively. The severity of penile and underlying erectile function are two key preoperative factors that determine the choice and success of surgery. Penile plication Penile plication procedures such as the Nesbitt procedure, the Yachia technique and Lue s 16-dot procedure are designed to shorten the longer side of the penis to compensate for the contralateral curvature. The advantages of plication surgery are that it is often simple, minimally invasive and likely to preserve underlying erectile function. The disadvantages are that it invariably shortens the penis, it is less effective when the penile curvature is greater than 60 degrees, and it will not correct any hourglass or hinge penile. 16 Peyronie s graft Graft surgery can be performed with plaque incision or partial excision. While the ideal graft material remains elusive, various autologous tissue dermis, vein or tunical, and allograft and xenograft materials such as pericardium, small intestinal submucosa and dermis, have been used and have shown satisfactory postoperative outcome. The advantages of graft surgery are that it is effective in treating larger penile curvature and complex penile and to a certain extent it preserves the penile length postoperatively. However, graft surgery can affect the underlying veno-occlusive mechanism, resulting in decreased penile rigidity postoperatively. 17 Postoperative penile care is advisable and often involves penile massage and stretch therapy, the use of oral phosphodiesterase type 5 inhibitors and/or use of an external penile traction device. 1 Penile prosthesis implant A penile prosthesis implant with straightening manoeuvres (eg penile remodelling) is indicated in men who have poor erectile function and/or medically refractory ED. While prosthesis implant alone is often enough to straighten a small penile curvature, those with residual curvature greater than 30 degrees may need manual modelling and other adjunctive manoeuvres. 18 The use of graft material placed over the prosthesis may be required in large and complex penile curvature but may increase the risk of infection. 1 FUTURE DIRECTIONS While the current therapies address the penile curvature, they are not very effective in treating penile pain and preventing recurrent penile curvature in the future. It is likely that the use of antifibrogenic and fibrinolytic agents such as transforming growth factor beta type 1 receptor inhibitors, phosphodiesterase type 5 inhibitors and matrix metalloproteinases may represent a novel targeted approach to treating PD in the future. 19 The increased knowledge and utility of translational research has resulted in the use of TRENDS IN UROLOGY & MEN S HEALTH JANUARY/FEBRUARY

5 22 stem cells to prevent fibrosis and restore erectile function in the animal model of PD 20 and may one day be applicable in the human. Declaration of interests: none declared. REFERENCES 1. Ralph D, Gonzalez-Cadavid N, Mirone V, et al. The management of Peyronie s disease: evidence-based 2010 guidelines. J Sex Med 2010;7: Mulhall JP, Schiff J, Guhring P. An analysis of the natural history of Peyronie s disease. J Urol 2006;175: Lue TF, Guiliano F, Montorsi F, et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med 2004;1: Smith JF, Walsh TJ, Lue TF. Peyronie s disease: a critical appraisal of current diagnosis and treatment. Int J Impot Res 2008;20: Pyror JP, Ralph DJ. Clinical presentations of Peyronie s disease. Int J Impot Res 2002;14: Hellstrom WJ, Feldman R, Rosen RC, et al. Bother and distress associated with Peyronie s disease. Validation of the Peyronie s disease questionnaire. J Urol 2013;190: Chung E, Yan H, De Young L, Brock GB. Penile Doppler sonographic and clinical characteristics in Peyronie s disease and/or erectile dysfunction: an analysis of 1500 men with male sexual dysfunction. BJU Int 2012;110: Chung E, Brock GB. Duplex sonographic study of impotent men with Peyronie s disease: is veno-occlusion the cause? J Sex Med 2011;8: Gonzalez-Cadavid NF, Rajfer J. Experimental models of Peyronie s disease: implications for new therapies. J Sex Med 2009;6: Brant WO, Dean RC, Lue TF. Treatment of Peyronie s disease with oral pentoxifylline. Nat Clin Pract Urol 2006;3: Chung E, DeYoung L, Brock GB. The role of PDE5 inhibitors in penile septal scar remodeling: assessment of clinical and radiological outcomes. J Sex Med 2011; 8: Levine LA. Current approach to the man with acute phase Peyronie s disease case presentation and discussion. J Sex Med 2011;8: Russell S, Steers W, McVary KT. Systematic evidence-based analysis of plaque injection therapy for Peyronie s disease. Eur Urol 2007;51: Abern MR, Larsen S, Levine LA. Combination of penile traction, intralesional verapamil, and oral therapies for Peyronie s disease. J Sex Med 2012;9: Chung E, Brock GB. Penile traction therapy and Peyronie s disease: a state of art review of the current literature. Ther Adv Urol 2013;5: Kendirci M, Hellstrom WJ. Critical analysis of surgery for Peyronie s disease. Curr Opin Urol 2004;6: Chung E, Cledinning E, Lessard L, Brock GB. Five year follow-up of Peyronie s graft surgery: outcomes and patient satisfaction. J Sex Med 2011; 8: Mulhall J, Ahmed A, Anderson M. Penile prosthetic surgery for Peyronie s disease: defining the need for intraoperative adjuvant maneuvers. J Sex Med 2004; 1: Gus S, Kadowitz PJ, Wellstrom WJ. Drugs of the future for Peyronie s disease. Med Hypotheses 2012;78: Lin CS, Lue TF. Adipose-derived stem cells for the treatment of Peyronie s disease? Eur Urol 2013;63:561 2.