Malignant and premalignant lesions of the penis
BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f1149 (Published 06 March 2013) Cite this as: BMJ 2013;346:f1149
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Dear Sir,
We welcome this excellent clinical review of malignant and premalignant lesions of the penis by Ayra and colleagues and thank them for citing our ‘Audit of referrals into a dedicated British penile cancer centre and sources of possible delay’, published in Sexually Transmitted Infections in 2009. We were, however, very surprised by the content of the published Rapid Response from members of the BASHH General Dermatoses Special Interest Group, which disputes their conclusion that patients with penile cancer are sometimes referred ‘in error’ to specialities other that Urology. Furthermore, they go on to state that a member of their group (CB) runs a penile clinic in one of the Genitourinary medicine (GUM) services that refer patients to the regional centre surveyed for our audit but was not asked for reasons perceived delay. Thus, implying criticism of ourselves.
We previously observed that despite the establishment of rapid referral pathways within the NHS for suspected urological cancers, patients with penile cancer continued to present in a delayed manner, frequently with advanced disease, had often been referred to other specialities and sometimes received inappropriate treatments. This prompted an audit of referrals to a regional specialist penile cancer centre following the introduction of the 2 week cancer target in December 2002. One hundred patients were diagnosed and treated over a 5 year period at our centre, 43% presenting with locally advanced disease. We concluded that the major source of delay results from patient reluctance to seek medical advice promptly and that the greatest impact on outcomes ought to be achieved by increased public awareness and education.
Nevertheless, approximately one fifth had been initially referred to other specialities. The most frequent indirect Urological pathway was via GUM departments across Merseyside and North Wales. Of these 13%, one third were self referrals and the remainder made by General Practitioners. Some patients were elderly and in stable relationships, where STI was unlikely. Only 2 were biopsied in GUM, with up to 6 months given to determine if the presenting lesion had settled down before referral to Urology. In summary, BASHH guidelines were not followed in a number of cases. Our senior author (NJP) was subsequently invited to speak at the regional GUM meeting and the results of the audit presented. This was attended by the majority of local Consultants and juniors and was held in the same hospital as CB holds a penile clinic. The audit was received with interest and fruitful discussion followed, it was also presented to regional Urologists.
Over the past 4 years we have observed that many Urologists within our region are immediately forwarding on GP referrals with suspected penile cancer to our centre, in an attempt to accelerate the pathway and offer immediate specialist assessment. Patients initially attending GUM also seem to be biopsied frequently and earlier when failing to respond to topical therapy. Furthermore, some GUM trainees have elected to attend several dedicated penile cancer clinics. We believe that GUM and Urology colleagues are working in harmony across our region to the benefit of patients, as recommended by the BASHH Specialist Interest Group. We do not believe that it would be appropriate for us to enter into a debate as to whether GUM physician organise dedicated genital dermatoses clinics, or not. However, we note that the Special Interest Group do not supply any scientific data to support this form of configuration and in particular to indicate that it improves management of suspected penile cancer.
Finally, before publishing articles which imply personal criticism of individuals, rather than scientific methods or opinion, we believe that there is an editorial responsibility to contact those involved, in order to permit a synchronous response, retraction or amendment. This protocol seems to have been overlooked in this instance.
Yours faithfully,
Nigel J Parr, Marc A Lucky, Beverely Rogers
Competing interests: No competing interests
Although my colleagues Manit Arya et al are to be congratulated on many aspects of their Clinical Review article on Malignant and Premalignant Lesions of the Penis, not least for attracting attention to the nasty and serious disease that is penis cancer, I can not let pass my disappointment at the inadequacy of the dermatological content.
The dermatological stance is that in a sophisticated health setting no one at all should contract penis cancer, let alone die from it or face mutilating treatment. This is because the risk factors and pre-disposing dermatoses are well known and characterized, allowing prevention early diagnosis and effective management.
Surely there are pitfalls, for example the differential diagnosis of morphologically banal red lesions and the perils of biopsy (right place/lesion, right time, right question asked of the pathologist, false negative/non-specific features).
Equally surely there are challenges, for example preventing and pre-empting pre-cancer and frank SCC in the growing cohorts of patients who are immuno-incompetent by virtue of disease, such as HIV, or treatment, as in transplantation medicine, oncology and haematology; the role of HPV vaccination for boys and men; and reducing the morbidity and mortality in the developing world such as India and South America where most men are uncircumcised.
The most egregious flaw is in the attention given to the genital skin disease, lichen sclerosus. The published risk of squamous carcinoma is up to 10% (not 2.3% as stated in the text nor ‘not known’ as stated in Table 4), although it has to be acknowledged some case series have been small, but also most have not involved long follow-up. Male genital lichen sclerosus is associated with about 50% of penis cancer, a fact buried late in the article, but not included alongside HPV (the other 50%) in the boxed Summary Points nor the paragraph headed ‘What are the risk factors for penile cancer?’, nor Table 1 (Risk factors for penile cancer). It is incorrect to say that ‘a pathological phimosis normally develops’. This is end stage disease. The vast majority of men with lichen sclerosus can, and should, be diagnosed much earlier on shrewd interpretation of symptoms (dyspareunia and urinary ‘dribbling’), signs (which may be subtle), intelligent consideration of the differential diagnosis, the place of biopsy, and response to treatment. All men can, and should, be cured with early intervention either by ultrapotent topical steroids or circumcision, hence avoiding deteriorating sexual function, devastating urethral involvement, pre cancer, cancer and the risks of mutilating treatment and death.
Perhaps these shortcomings have arisen because of too ambitious a scope (it's a big title), poor methodology (the Sources and Selection Criteria list inadequate search terms eg lichen sclerosus was omitted) and inattentive reviewing.
I repeat, the risk factors of penis cancer (uncircumcised, phimosis, poor hygiene, chronic irritation and inflammation, scarring, smoking, HIV (x5-6), photochemotherapy, iatrogenic immunosuppression, radiotherapy) and its causes (HPV and lichen sclerosus and the pathobiology of both) are well known and delineated, and the pre-cancerous dermatoses (lichen sclerosus, lichen planus) and clinical manifestations of pre cancer/carcinoma in situ (Bowen’s disease, erythroplasia of Quyrat, Bowenoid papulosis) are relatively well characterized, clinically and histologically. Prevention, early diagnosis and effective treatment of penile pre-cancer and the prevention of frank invasive cancer are all attainable goals, hence my response.
Porter, WM, Francis N, Hawkins D, Dinneen M & Bunker CB. Penile intraepithelial neoplasia: clinical spectrum and treatment of 35 cases. Br J Dermatol 2002;147:1159-1165.
Bunker CB. The dysfunctional foreskin. JEADV 2004;18:70.
Bunker CB. & Neill SA. The genital, perianal and umbilical regions. In: T.Burns, S. Breathnach, N.Cox and C. Griffiths, (eds.) Rook’s Textbook of Dermatology. 8th edition. Wiley-Blackwell, New York. 2010;71:1-102.
Neill SM, Lewis FM, Tatnall FM & Cox NH. British Association of Dermatologists’ guidelines for the management of lichen sclerosus 2010. Br J Dermatol 2010;163:672-82.
Bunker CB. Comments on the BAD guidelines for the management of lichen sclerosus Br J Dermatol 2011;164:894-5.
Rao A & Bunker CB. Male genital skin biopsy. Int J STD & AIDS 2011;22:418-9
Edmonds E, Hunt S, Hawkins D, Dinneen M, Francis N & Bunker CB. Clinical parameters in male genital lichen sclerosus: a case series of 329 patients. J Eur Acad Dermatol Venereol 2012;26:730-7.
Bunker CB. Occlusion, urine and genital lichen sclerosus. Indian J Dermatol Venereol Leprol 2012;78:367-8.
Bunker CB, Patel, N & Shim TN. Urinary voiding symptomatology (micro-incontinence) in male genital lichen sclerosus (MGLSc). Acta Derm Venereol 2013;93:216–256.
Competing interests: No competing interests
Ayra and colleagues provide an excellent clinical review. As penile cancer is a rare condition, men with the condition are unlikely to ever meet anyone outside their clinical team who has had direct or indirect experience of their cancer. Resources about the condition and the experiences of other patients will be useful to help facilitate informal learning about how to adapt with the changes they will experience in their body. Alongside those resources highlighted by Ayra and colleagues, the award winning www.healthtalkonline.org has published a module on penile cancer.
Developed as part of the Patients' Experiences of Penile Cancer (PEPC; 1) study, the penile cancer module consists of almost 300 audio, text and video clips of men talking about their condition. The site has 24 themes across five main categories; early signs (signs & symptoms; seeking help), diagnosis (assessment; hearing the diagnosis; professional support; information; the support of others; telling others), treatment (types of surgery; lymph node removal; preparation and anaesthetics, recovery from surgery; additional treatments; considering complementary and experimental treatments) and after treatment (manhood, mental well-being and self-confidence; feelings & emotions; work and finances; aftercare & checkups; physical health; using the toilet; sex & relationships; lymphoedema and the impact of lymph node removal). The final category included reflections on sharing their experiences and the main messages they would give to health professionals.
The Royal Society 23rd October 2013, the penile cancer module had over 60,000 hits in its three months and has been featured in national, regional and medical press. For example, Ally Fogg, a is a Manchester-based writer and journalist, has written about the module in The Guardian (2) and the Big Issue In The North. The BBC Radio 4 Inside Health programme broadcast a short report on penile cancer (where we hear from Asif Muneer, the last author of the paper in question), which has kindly been made available on the penile cancer module (in the right hand 'swim lane' on the front page of the penile cancer module).
PEPC also produced a travelling exhibition of artwork inspired by the research alongside quotes from the www.healthtalkonline.org module. The exhibition consists of 29 banner stands that can be adapted to different environments. Anyone interested in hosting the exhibition should get in touch.
1. Branney, P., Witty, K., & Eardley, I. (2011). Patients' Experiences of Penile Cancer. European Urology, 59(6), 959-961. dx.doi.org/10.1016/j.eururo.2011.02.009
2. Fogg, A. (2012). When is it OK for a cancer campaign to be sexy? Comment is Free, The Guardian, downloaded 24th March 2013 from http://www.guardian.co.uk/commentisfree/2012/oct/24/cancer-campaign-sexu...
Competing interests: PEPC is independent research commissioned by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0808-17158). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Arya and colleagues provide an excellent review of the prevalence, risk factors, presentation and management of penile cancer and pre-cancer (BMJ 2013; 346: 1149ff). However we dispute their conclusion that initial referral to specialties other than Urology as an 'error’, based on a single paper by Nigel Parr and colleagues.
Firstly, one of us (CB) runs a penile clinic in one of the Genitourinary medicine services that refer patients to the regional centre surveyed for the paper by Parr and colleagues but was not asked for reasons for the perceived delay. GUM clinics deal with many benign lesions of the penis that are often difficult to distinguish from premalignant lesions, and the delays in onward referral are not due to inappropriateness of the initial referral. In fact, patients may fail to attend their appointments, decline biopsy or opt for a trial of empirical treatment before tertiary referral.
Secondly, with the regular updating demanded of Genitourinary services for genital dermatoses, is usually easy to spot a penile cancer but PIN can be difficult and we would suggest that specialist Urology clinics would be completely swamped with conditions like Zoon’s balanitis if we did not stop to biopsy lesions first.
Thirdly Genitourinary clinicians are at an advantage to recognise normal and abnormal lesions on the genitalia due to the sheer volume of genital examinations done on a daily basis and the experience gained in seeing genital lesions. Most clinicians in Genitourinary clinics are able to recognise genital lesions and know whom to refer within the Department or in the hospital if a lesion appears suspicious. Specialist multidisciplinary clinics are also available such as the one led by Prof C Bunker at Chelsea & Westminister Hospital. We think this underlines the importance of the provision of specialist genital dermatosis clinics in the Genitourinary setting and the necessary funding that these imply. These clinics have clear pathways for prompt referral and appropriately use the 2 week cancer wait access that Arya and colleagues urge us to use. Genitourinary clinics are open to patient self-referral with access within 2 working days, thus helping and not delaying diagnosis and management. The only delay that some Genitourinary services may experience is the inherent delay in some trusts where internal consultant to consultant referrals are not allowed and patients have to request a referral letter to Urology from their general practitioner.
Patient and physician education is undoubtedly the key to prompt referral. We agree with Arya and colleagues who quote embarrassment as a reason for delay in presentation and education may reduce this barrier. However, where clear pathways have been agreed by Genitourinary and Urology colleagues working in harmony, penile cancer and precancerous lesions are managed well and can benefit quality of life and outcomes for our patients.
Competing interests: No competing interests
malignant lesions of the penis are generally unfortunate spectres in our own surgical catchment areas; the impossible combinations of a man who presents so late, the diagnosis is visually obvious and yet reluctant to part with the organ were there to be any prospect of prolonging his life.
I have only had to do total penectomies in my personal experience since the stage of presentation left no realistic alternative.
often in some of these cases im reminded of women who refuse timely surgery for an early breast cancer until very late and you can then only offer a toilet mastectomy.
i use every opportunity i have to urge pts on to circumcisions even if its protective umbrella for cancers is lost after a certain age limit.
the hygiene involved, the easier visibility and thus earlier diagnosis ( facilitated by sight from patient or girlfriend and of course the doctor) make circumcision more than woth it in these matters.
There are lingering misconceptions about the effect of circumcision on either virility or desire or the ability to fully satisfy partners during coitus from mere loss of the preputial segment; it is often perceived as loss of penile bulk and thus loss of vaginal fit. some are easily educated to the contrary, a few will rather die of their lesions than even a mere circumcision.
A few teenagers are increasingly falling for the habit of implanting bead-like object under penile skin on the dorsum of the shaft to act as mechanical clitoridal stimulants during coitus. sometimes, a foreign body reaction with granulomatous encapsulations build around these foreign bodies creating anatomic
artefacts that can confound the physicians in clinical evaluations.
ulcers from frictional rubs have sometimes ensued from these beads. and then fester into previously undescribed clinical morphologies.
Florid poorly controlled diabetes is a frequent source of balanoposthitis in this island ( east caribbean) and when seen in the uncircumcised can have all of the look of something malignant or premalignant.
histology remains the salvaging light in most of the cases.
by and large, cancer of the penis is epidemiologically uncommon in our parts but when they do come, they so late and reluctant to cooperate till even later.
Competing interests: No competing interests
I read your article on malignant and premalignant lesions of the penis with much interest, because experts cured my penile cancer in 1979, and I am still enjoying marital sex at the age of 76!
When a physician in the United States in 1970, I noticed a red spot on my glans penis. A biopsy showed a carcinoma-insitu (Erythroplasia of Queyrat). The oncologist built a plastic clamp, which held my penis up while I received 6000r of radiotheraphy daily for 20 weekdays The radiotheraphy was curative for nine years.
But in 1979 I developed an ulcer under the glans and the late, brilliant surgeon, Bill Hendry, did a partial penectomy and then referred me to an oncologist who gave me a course of Bleomycin chemotherapy which was curative.
I am very grateful to all the experts who treated me in Washington, DC and London. Recently, you published a long obituary on Bill Hendry, a great man and surgeon.
I hope penile experts and their patients will be more hopeful because of my cure.
Competing interests: No competing interests
Re: Malignant and premalignant lesions of the penis
We acknowledge Professor Chris Bunker’s expertise and contribution in the field of genital lichen sclerosus et atrophicus (LS). However, the remit of our article [1] was to cover all premalignant and malignant disease of the penis and not solely LS.
We emphasise the risk of developing penile squamous cell cancer (SCC) in any individual patient with LS is uncertain – this is the same conclusion reached by the British Association of Dermatologists who go on to suggest that the risk may be about 5% [2]. In our clinical review we have quoted the largest published series of patients with genital LS in a single centre - on retrospective analysis of 522 men with this condition it was found that 2.3% (12 patients) had treatment for SCC of the penis [3]. In fact in another large retrospective review of 329 men with genital LS published by Professor Bunker’s own group only 5 patients were confirmed to have associated penile carcinoma in situ and furthermore on reviewing these mens’ attendances, records and follow-up letters it was demonstrated that not one had developed invasive SCC [4]. Many smaller retrospective case series exist with limited follow-up and there is a lack good quality studies with multivariate analysis. The role of LS in the carcinogenic pathway for penile cancer still remains unclear and the absolute risk of developing penile SCC in these men is as yet uncertain.
1) Arya M, Kalsi J, Kelly J, Muneer A. Malignant and premalignant lesions of the
penis. BMJ. 2013 Mar 6;346:f1149
2) Neill SM, Lewis FM, Tatnall FM, Cox NH. British Association of Dermatologists’ guidelines for the management of lichen sclerosus 2010. Br J Dermatol 2010;163:672-82.
3) Depasquale I, Park AJ, Bracka A. The treatment of balanitis xerotica obliterans. BJU Int 2000; 86:459-465
4) Edmonds E, Hunt S, Hawkins D, Dinneen M, Francis N & Bunker CB. Clinical parameters in male genital lichen sclerosus: a case series of 329 patients. J Eur Acad Dermatol Venereol 2012;26:730-7
Competing interests: No competing interests