Spotlight: Peyronie’s disease management

Peyronie’s disease (PD) is a well described fibromatous disorder characterised by plaque formation in the tunica albuginea and an associated variable penile angulation in the erect state. Despite current studies reporting a prevalence rate of 3-9% of the male population,¹ the aetiology is still not fully understood. Additionally, these figures may be an under representation of the true prevalence of this disorder due to a variety of factors including the patient’s unwillingness to discuss the condition or high symptomatic threshold for patient self referral.²

PD is associated with a number of reported comorbidities, (Table 1) with erectile dysfunction being be found in over 50% of cases. The presence or otherwise of erectile dysfunction plays a significant and pivotal role when managing such patients and in particular when surgical intervention is deemed necessary.³

The current age demographic of patients affected by this benign disorder ranges between 40 and 70 years with peak incidence being in the sixth decade between 50-55 years of age⁴ Published retrospective studies pertaining to the prevalence of PD in middle age and those under 40 years of age are widely available,^5,6 however there is a paucity of data focusing exclusively on patient cohorts over the age of 60 years. This article aims to review current management of Peyronie’s disease whilst concentrating on its pertinence to the older population.

Table 1. Associated comorbidities

Diabetes

Hypertension

Cardiomyopathy

Smoking

Alcohol

Lipid abnormalities

 

The exact definition of what can be described as €˜elderly’ is still subject to much debate. The World Health Organisation (WHO) appears to use chronicity as a principle guide suggesting the age of 65 whilst the unofficial United Nations cut off is 60 years reflecting disparities in health between developed and developing nations. Sexual intimacy however, is quite rightly, no longer affiliated with the younger population alone.  Although we understand sexual function to naturally decline with advancing age, 60% of the elderly population still expresses their need to maintain a healthy sexually active life.⁷Consequently, it is important to appreciate how sexual or erectile dysfunction in elderly men as a result of PD may negatively affect overall patient and partner quality of life.

Epidemiology of Peyronie’s disease

The epidemiological data on the prevalence of Peyronie’s disease amongst the elderly has not been well published. Schwarzer et al,⁸ eluded to the age related increased prevalence found when completing a cross-sectional community based survey study on 4432 men in Cologne, Germany. They reported self diagnosed, localised penile induration in 4% and 6.5% of patients within the 60-69 and >70 years category respectively. Whilst this data conflicts with most series reporting a reduction in incidence over the age of 55 years, it may well transpire with further study that a second incidence peak occurs in the eigth decade.

Rhoden et al⁹ looked specifically at the prevalence of PD in >50 year olds originating from South Brazil. Of the 954 men included in the study, they identified percentage prevalence to be 4.49% and 3.81% in the 60-69 and 70-79 years old groups respectively suggesting there to be a reasonable cohort of patients in older age bands who suffer with PD.

Natural History

The natural history of PD is very well reported and follows a classical pattern of an initial acute often painful stage during which the disease and associated angulation increases and which typically lasts for up to 18 months. This is then followed by a quiescent phase characterized by stability, pain resolution and an absence of further angulation progression. Once the disease has been stable for 3 months, furher exacerbation is very unlikely

Non-operative management

Treatment options for PD are varied and can be subdivided into different categories. Oral therapies include the use of vitamin E, tamoxifen, colchicine, pentoxifylline and other newer pharmacotherapies indicated in the early (active) phase PD or in patients not suitable for surgical intervention. They have varying benefits in preventing PD progression and in reducing penile plaque size, pain and/or the degree of curvature.¹⁰  The specific role of oral therapies is not well defined and often contradictory with only low grade evidence supporting its efficacy,³ however these options may be considered more preferable to elderly patients with PD due to their low risk index, especially in those unsuitable for surgery.

Vitamin E

Vitamin E is shown to have anti-oxidant properties by hindering free radical production involved in propagating penile fibrosis.¹⁹ It is very commonly utilised as first line therapy for Peyronie’s disease due to it is safe administration and relatively low cost. Recent double-blind, placebo-controlled studies have not suggested significant benefit in using Vitamin E²⁰ and current international guidelines state that evidence for its use is equivocal. Nevertheless, there are promising reports proposing Vitamin E’s beneficial synergistic properties when given alongside intra-lesional therapies, although the exact mechanism behind this is still not fully understood.

Colchicine

With its principle mechanism of action via the inhibition of collagen deposition and fibrosis, colchicine helps to down regulate collagenase activity and thus reduce plaque formation in PD.¹⁷ Common side effects include nausea, vomiting and bowel disturbances. Studies looking at the efficacy of combination therapy with Vitamin E and colchicine in early stage PD have shown significant improvements in penile plaques size and degree of curvature during a 6 month period.¹⁸ Further studies however, are required to assess its benefit over other non-surgical therapies.

Pentoxifylline

Non selective phosphodiesterase inhibitors such as pentoxifylline, unlike their phosphodiesterase inhibitor counterparts, are found to have anti-fibrotic and anti inflammatory properties acting in a number of varied ways. In PD it is proposed to be via reducing TGF-β-1 mediated inflammation and deposition of type 1 collagen in plaques.²⁰ There is supporting evidence reporting an improvement in patients International Index of Erectile Function score (IIEF) and penile curvature when treated with pentoxifylline compared with placebo. Other studies have commented on its benefits in reducing calcium content and elastogenesis²² suggesting this to be a viable treatment option of Peyronie’s disease even in the elderly.

Tamoxifen

Albeit predominantly known as a selective oestrogen receptor modulator, tamoxifen also plays a role in down regulating fibrogenesis of penile plaques. Unfortunately the majority of current literature has not shown a significant benefit in its use over placebo trials in terms of improving penile pain, curvature or plaque size,²³ but despite this, its use is common in patients with PD. With this proven lack of efficacy and its side effect profile including retinopathy, pancytopenia and thromboembolisms, this should not be considered for PD treatment in the elderly.

Potassium aminobenzoate (Potaba)

Potaba has been available as treatment for early phase PD for over 40 years.  Its anti-fibrotic properties help to stabilise serotonin- monoamine oxidase activity and inhibit fibroblastic glycosamineglycan secretion (24). Recent guidelines advocate potassium based oral treatments as they may result in significant reduction in penile plaque size, pain, as well as stabilising  penile curvature.³ Additionally, due to its tolerability and availability, it is sensible to consider potaba as a first line therapy, (12g daily in divideddoses) of acute phase PD in elderly patients.

L-Carnitine

Carnitine is thought to enhance mitochondrial respiration and consequently reduce free radical formation that may propagate PD.²⁵ This theory however has not been fully established. There is very weak evidence behinds its use as a PD treatment option and studies have shown its lack of superiority over placebo in treating PD and hence this can no longer be recommended.²⁰

Intra-lesional therapy

The use of verapamil and steroids as intra-lesional therapy options have yielded results worthy only of low grades of recommendation for the treatment of PD with only intra-lesional interferon having any reported beneficial effect on all three aspects of PD,  plaque size, penile curvature and pain.¹⁰

Steroids

The use of steroids is thought to have both immune suppressive properties and inhibitory effects on phospholipase C. A recent review article by Gokce et al suggests that the majority of current data fails to support the use of steroids in the treatment of PD in any stage.¹ This review and its conclusion is supported by further studies and as such, intra-lesional steroid are not recommended. Additionally, with its well established side effect profile including both tissue atrophy and difficulty of subsequent surgical procedures, steroids would not be  advised in the elderly cohort.

Collagenase

The European Association of Urology (EAU) 2014 guidelines, gives a grade C recommendation for the use of intra-lesional collanenase ,(grade 2b evidence) in the treatment of PD. Intra-lesional clostridial collagenase results in a  significant decrease in deviation angle, plaque width and plaque length. It is a physiological enzyme capable of breaking down type II collagen associated PD progression.²⁶ Both in vivo and in vitro studies have shown positive reports intra-lesional therapy stating improvements in penile curvature, pain and restoration of intercourse in over 60% of patients treated after 4 weeks,²⁷ With only minimal side effects relating to localised pain, bruising and rarely, corporal rupture; collagenenase has a place for treatment in both acute and chronic phase PD.¹ The U.S. FDA has recently approved, Xiaflex (collagenase clostridium histolycum) as the first non-surgical treatment option for men with a palpable plaque causing curvature of at least 30 degrees on erection. This may be regarded as a viable treatment option for elderly patients with PD.

Verapamil

Acting as calcium channel blocker antagonist, early studies by Roth et al described its physiological use in PD to be associated with increase in collagenase activity and reduction of fibroblastic activity of PD plaques.²⁸ To date, there has still only been one case controlled study comparing topical verapamil gel with placebo conducted by Rehman et al demonstrating significant improvement in erectile function and plaques softening but without impact on penile curvature.²⁹ Verapamil has been shown to only cause mild adverse effects such as nausea and penile pain. As yet, there have been no reports of systemic cardiac disturbances making this a very viable treatment option for elderly patients in reducing early PD progression.

Non surgical therapies

Published data on the use of other non-invasive treatments such as extra corporeal shockwave treatment and penile traction devices display similar efficacious inconsistencies and as such, are generally not recommended outside properly conducted clinical trials, and this is the view currently endorsed by the National Institute of Health and Care Excellence, NICE.

Extra corporeal Shockwave treatment (ESWT)

The use of high pressure, low frequency sound waves applied to the affected plaque tissue has been readily proposed as a viable treatment option for Peyronie’s disease. The exact mechanism of action is still not fully understood. Two hypotheses postulated thus far indicate that treatment results in either heat enhancing inflammation with associated plaque lysis and resorption over time or direct damage and remodeling of the penile plaque itself. The majority of current literature has shown no benefit of using ESWT in reducing penile curvature or plaque size. Only one double blind study conducted by Palmieri et al, resulted in a significant improvement of pain symptoms only.³⁰The EAU have therefore labeled a 1b level of evidence for its penile analgesic properties only.³

The National Institute of Clinical Excellence (NICE) advocates the safety of this procedure reporting only transient findings such as urethral bleeding, haematoma formationand skin discolouration. Despite comparative studies revealing evidence of improved Penile curvature and sexual performance in patients using ESWT, caution should be exercised when interpreting these results given the natural history of the disease, lack of data including placebo/controlled arm and absence of valid outcome measures,³¹

Penile traction

The EAU guidelines have indicated a very low grade of recommendation for the use of penile traction in treating PD patients (3). The concept supporting penile traction is provocation of the synthesis of new collagen after reduction of penile tensile strength. There are no published studies reporting its benefits in treating PD or its long term efficacy and at present this cannot be recommended in the elderly age group.

Surgical intervention

Counseling and investigations

Comprehensive preoperative counseling is essential in order to ensure the highest post-operative satisfaction rates.¹³ The responsible clinician should discuss the operative procedure, risks and potential complications (both frequent and serious) in detail. Time should be spent on discussing ideas, concerns and realistic post operative expectations as patient dissatisfaction despite good surgical results can be difficult to manage.¹⁵

Surgery is performed for a functional purposes and the focus is on restoring adequate penile straightening to enable penetrative sexual intercourse, ideally with a residual deformity of less than 20 degrees³³ although this in part depends upon the direction of angulation with residual dorsal curvature being more acceptable than ventral. Due to the nature and location of the operating field, specific risks such as penile numbness and loss of length, bruising/haematoma formation, curvature recurrence, possible need for circumcision at time of operation and palpable sutures beneath skin site must all be included within the consent for those opting for surgical intervention.³²

For the elderly population, supplementary risk factors for example diabetes and peripheral vascular disease should be well controlled and fully optimized pre operatively. Operative planning requires a discussion of full sexual history including sexual rigidity and realistic post-operative outcomes. The use of the International Index for Erectile Function (IIEF) is a suitable objective tool that can assess normal erectile function preoperatively and can evaluate the degree of post procedural improvements in terms of erectile capacity (34). The Peyronie’s Disease Questionnaire PDQ, a disease specific survey is an alternative tool that  has been recently validated with two phase 3 clinical trials for collagenase clostridium histolyticum,³⁵

Operative management

Surgery still remains the gold standard treatment for stable penile curvature deformities^3,11 however; this should be approached with more caution in older patients. The main criteria for surgery include: stable disease (for at least 3-6 months), excessive plaque formation, failed conservative therapy and inability to perform sexual intercourse.¹⁰ In those who possess severe PD with penile curvature greater than 60 degrees, surgery may be considered as first line treatment,²⁶

The PD surgical algorithm is conventionally used to delineate the ideal surgical course of management. Choice of penile lengthening or shortening procedures are based on presence or absence of erectile dysfunction,  degree of erect penile curvature, evidence of destabilising deformity and  post-operative predictive length of penis,¹²

Penile shortening procedures

Penile shortening surgery consists largely of a corporal plication procedure which aims to create symmetry with the Peyronies plaque by placing sutures on the contralateral aspect of the corporal bodies. A tunical ellipse or incision may or may not be performed to facilitate curvature correction and suture burial and the plication may need to be performed at several sites depending upon the degree and complexity of the PD.

Classically, plication corporoplasty is performed in patients with stable disease, curvature less that 60¹⁰,  good pre-operative erectile quality and with acceptable post surgery penile length.³.

Complications include suture granuloma (0-1.9%), penile haematoma, urethral injury, phimosis (0-4.8%), narrowing and indentation of the penile shaft (0-16.7%), and penile or glans hypoesthesia (0-21.4%).³⁴ Erectile dysfunction occurs in up to 10% of men post-operatively, and particularly in the elderly, this is a vital component of the pre-operative patient assessment as age is the single most influential factor for the development of erectile dysfunction.

Penile lengthening procedures

The operative site of focus in lengthening procedures is on the concave side of the curvature, the plaque itself. This comprises of either excision or incision of the plaque with a view to filling the resultant tunical defect with a suitable graft eg : Saphenous vein, bovine pericardium, artificial materials.

In contrast to penile shortening procedures, these are performed on patients with the presence of special deformities e.g hour-glass or hinge or severe penile curvatures > 60^o which in turn implies reduced predictive post procedural penile length. Complete plaque excision is not advised, and preservation of viable tunica should be of utmost importance, however remaining microscopic plaque may provide an area for post operative contracture formation.³⁴ EAU guidelines report success rate figures ranging between 74-100% for penile straightening however comparative studies show variability in these figures depending on the type of graft used, with autografts providing the best results.

Special attention must be given to penile lengthening procedures requiring grafting in the elderly population. Lengthening procedures have an approximately 30% risk of post operative erectile dysfunction, which is heavily increased in those over 60 years and should therefore not be considered in patients of this age group without careful consideration and pre-operative counselling. Other complications include haematoma, (0-4.5%), recurrence (0-16.7%), graft infections, fibrosis, contractures, penile numbness and neuropraxia.^12,32

Rehabilitation also plays a major role in reducing the incidence of postoperative erectile dysfunction and improves penile length,¹²This comprises of a series of external penile traction exercises and graft massage for 4 weeks, beginning 2 weeks after surgery. Rybak et al demonstrated statistically significant improvements when comparing length preservation in patients undergoing tractions therapy vs no therapy for both post-opertive plication and graft operations.³⁶

Penile implant surgery

The use of prosthetic penile implantation is reserved for patients with PD associated with significant erectile dysfunction, unresponsive to conservative management. This requires either an inflatable (2piece/ 3 piece) or a semi-rigid prosthetic device. Inflatable devices provide a more €˜natural’ erectile experience with on demand rigidity compared to the permanent rigidity of their semi rigid counterparts. Penile prostheses do not offer the same level of increased girth and length associated with a natural erection and patients need to be aware of this during the consent process. The prime aims of the prosthesis are to offer rigidity and straightening and with this in mind penile moulding may be required if the curvature is significant.

Comparative studies looking at success rates of penile prosthetic implantations conducted by Carson et al, reported 84-100% and satisfaction rates, upwards of 91%,¹² These figures are slightly   magnified compared to those reported by EAU of 70-87% after appropriate consultation,³ Complications include mechanical failure, persistent curvature, device difficulties, erosion and device related infections (2-3%).

In addition to the well documented complications and medical- legal factors surrounding implant operations, there are a number of additional facets to consider when dealing with older patients. Careful patient selection and counseling is incumbent when opting for this surgery. Candidates must be in good enough health, psychologically and intellectually able to cope with the prosthesis, and have the manual dexterity to manage the prosthesis, especially inflatable implants either independently or with assistance from their partner.¹⁵ There is a higher prevalence of conditions such as dementia in the older population, making functionality and understanding the device a challenge and in addition, handling issues such as arthritis may hamper the dexterity require to operate the prosthesis with confidence in the home setting. The elderly population is living longer with a larger number of chronic conditions in the community setting. Risk factors such as diabetes and longstanding steroid use for other chronic conditions can amplify the predisposition to implant infections, which are reported to carry a 2-3% rate in those without risk factors.³

Despite this advancing age should not be considered a limiting factor for prosthetic penile implantation (PPI). Moreover, Chung et al’s retrospective review demonstrated men >75 to have similar PPI clinical outcome and excellent satisfaction rates compared to those <75, however this data was not statistically significant.¹⁶

Conclusion

The elderly population is continuing to grow and our threshold for offering medical and even surgical treatment is increasing likewise. At present there is limited published literature on elderly care management of PD as a distinct entity with all series combining men of all ages

This review aims to highlight those aspects pertinent to the elderly and it is hoped, shows that with cautious patient selection and detailed counseling, this age group should be considered for the majority of management options their younger counterparts enjoy.

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Geoffrey Ibe is  CT Trainee Urology Manchester Royal Infirmary

Arie Parnham StR Trainee Urology Manchester Royal Infirmary

Ian Pearce Consultant Urological Surgeon Manchester Royal Infirmary

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This article was first published in GM Journal