Penile cancer is a rare male genital cancer which presents in older men in the 6th or 7th decades. However, the disease is not limited to the older population and younger men with risk factors can also develop penile cancer. Some of the highest reported incidence is in South America and parts of Africa where neonatal circumcision is not commonly practiced. North America and Europe have a low incidence and there are very few cases in countries where religious or ritual neonatal circumcision is practiced.
The incidence of penile cancer in the United Kingdom (UK) is between 1.5 to 2.5 per 100,000 men with between 6-700 cases per annum. Significant regional variation exists with areas of greater socio-economic deprivation suffering the highest incidence. From 2013-2017 in England, incidence rates in males were 52% higher in the most deprived quintile compared with the least.
Risk Factors for Penile Cancer
There are several risk factors associated with the development of penile cancer. The accepted risk factors include phimosis (nonretractile foreskin), high risk HPV16 and 18 infection and lichen sclerosus which is a chronic inflammatory disease affecting the foreskin. Additional risk factors include poor genital hygiene, smoking, obesity and exposure to ultraviolet light A (PUVA).
Lichen sclerosus can be manged using topical steroid treatment but failure to respond should be followed by a circumcision. The chronic inflammation can lead to the development of differentiated PeIN which is the non-invasive pre-malignant phase. With HPV associated pre-malignant disease, undifferentiated PeIN can develop before invasive disease and in some cases both differentiated and undifferentiated PeIN may co-exist. The implementation of gender neutral vaccination programmes using the nanovalent HPV vaccine will eventually reduce the incidence of HPV related cancers which also include head and neck cancers, vulval and anal cancer.
Anatomy of the penis
The penis compromises a shaft which is formed from 3 cylinders, corpus cavenosum of which there are two and contain the vascular smooth muscle surrounded by the tunica albuginea. The third component is the corpus spongiosum surrounding the urethra. The head of the penis is the glans and this is normally covered by the prepuce which has an inner mucosal layer. The neurovascular bundle runs on the dorsal aspect of the shaft of the penis and is covered by the Bucks fascia.
Penile Cancer Pathology
Squamous cell carcinoma accounts for greater than 95% of cases and most commonly affects the glans and/or inner foreskin. The squamous cell cancer has several subtypes with the sarcomatoid subtype being very aggressive. Rarer pathological subtypes include mucosal melanoma and sarcoma. The treatment of the primary lesion is standard for all the subtypes and is mainly directed by the extent of invasion into the proximal penis. Commonly the tumours are limited to the foreskin or glans penis and these are staged as T1 and T2 tumours. However, more extensive invasion into the corpus cavernosum requires more extensive surgery to ensure clear margins and these are staged as T3.
The lymphatic drainage from the penis is predictable and initially drains to the inguinal lymph nodes bilaterally. The involvement of the inguinal lymph nodes is the most important prognostic indicator for patients with penile cancer.
Management of the primary lesion
The management of premalignant disease is primarily by offering a circumcision and adjuvant topical chemotherapy such as 5-FU or immunotherapy such as imiquimod can be used for refractory areas of disease. Where available CO2 laser can also be effective. In some cases with extensive glans involvement which persists, glans resurfacing can be performed. This is a surgical procedure which excises the glans epithelium and replaces the defect with a split skin graft. Circumcision can also be used to excise tumours on the foreskin and wide local excision of small volume glans lesions is also an option. Surgical techniques are aimed to preserve as much penis as possible so that patients can void standing up and have enough length for penetrative intercourse. Where lesions are invading the glans penis, a glansectomy (removal of the glans cap) with reconstruction of the neoglans using a split skin graft is now a standard of care with low recurrence rates of less than 10%.
If there is invasion into the corpus cavernosum then a partial penectomy is required or for more extensive lesions, a subtotal or total penectomy. For patients who are motivated and have a good performance status, reconstruction of a neophallus using a free flap can be offered following a subtotal or total penectomy.
Management of Inguinal Lymph Nodes
As mentioned already the most important prognostic indicator is the presence of metastatic disease in the inguinal lymph nodes. There is a high risk of metastatic disease being present in palpable nodes. In impalpable lymph nodes the risk of micrometastatic disease is upto 25%.
Again minimally invasive options such as dynamic sentinel lymph node biopsy and videoendoscopic inguinal lymphadenectomy are now used to reduce the morbidity associated with inguinal lymphadenectomy which includes wound complications and lower limb lymphoedema.
Systemic Treatment Options
The response to systemic treatment remains poor although there is a role for neoadjuvant treatment in more extensive disease prior to surgery. Immunotherapy is still in the trial phase but represents an alternative option for patients with systemic disease.
Penile cancer is a rare malignancy and the prognosis for patients with systemic disease remains poor. However, those with localised disease to the penis or limited disease in the inguinal nodes have a good prognosis.
About The Urology Foundation
The Urology Foundation is the UK’s only charity representing all urological diseases including prostate, bladder, kidney and male reproductive cancers and non-malignant conditions including incontinence, urinary tract infections (UTIs), erectile dysfunction and kidney stones. We are committed to improving outcomes, quality of life and saving lives through investment in ground-breaking research, training in technical skills and innovative technologies and practices, education and awareness. Working with researchers, urologists, nurses and allied healthcare professionals, influencers and decision makers, patients and their families and those with an interest in urological diseases, we are improving the nation’s urology care.
Professor Asif Muneer MD FRCS (Urol), Consultant Urological Surgeon and Andrologist – Clinical Lead Urology, NIHR Biomedical Research Centre UCLHProfessor of Urology and Surgical Andrology, Department of Surgical Biotechnology, UCL
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