Penile cancer is a rare malignancy in the UK (Cancer Research UK (CRUK), 2018). When diagnosed early, the prognosis is excellent, but for those who present with nodal metastases, the prognosis dramatically worsens (Djajadiningrat et al, 2014). It predominantly occurs on the foreskin or glans penis, and surgery is the gold standard for treating this condition. Traditionally, penile cancer was managed at numerous centres across the UK and the standard treatment was aggressive radical surgery (Vanthoor et al, 2019). Unfortunately, such a radical approach often resulted in significant physical change, which was difficult for those affected to accept psychologically and adjust to (Hadway et al, 2016). To better address the needs of this patient group, 2012 saw the creation of centralisation of penile cancer services, which has led to the development of highly specialised multidisciplinary teams, improved patient care with more appropriate management, and better overall outcomes (Vanthoor et al, 2019).
Penile cancer can be devastating for patients physically and psychologically. Treatment has a potentially significant effect on the individual because surgery may impact on social interactions, self-esteem, sexual function and body image. Nurses play an integral role in supporting patients throughout their cancer journey by providing education, information and support (Henry, 2015).
Anatomy and physiology
The penis has a root and a shaft. The root anchors the penis in the perineum and the shaft is the external visible part of the organ, which ends in an enlarged triangular tip known as the glans penis, from which the urethral opening (meatus) is seen (Figure 1). The glans penis is covered by loose skin known as the prepuce or foreskin, which can be retracted.
Internally the penis comprises three cylindrical bodies of erectile tissue and smooth muscle (Figure 2). The erectile tissue is supported by the fibrous tunica albuginea and covered with skin. The two main erectile bodies that make up the majority of the penis are called the corpus cavernosa and between them is the corpus spongiosum containing the urethra. The male urethra is about 19-20 cm long and consists of three parts, the prostatic urethra, the membranous urethra and the penile urethra, and it is the latter part that lies within the corpus spongiosum of the penis, terminating at the urethral meatus (external urethral opening) (Waugh and Grant, 2018). It is through this orifice that both urine and sperm are excreted.
The proximal ends of the corpus cavernosa form the crus of the penis, which are surrounded by an ischiocavernosus muscle that is anchored to the pubic arch of the bony pelvis.
Arterial blood is supplied by deep, dorsal and bulbar arteries of the penis (Figure 2), which are branches of the internal pudendal arteries. A series of veins drain blood to the internal iliac and internal pudendal veins. The penis is supplied by somatic and autonomic nerves (Figure 1) (Waugh and Grant, 2018).
Epidemiology
Penile cancer is a rare disease but, in recent years, its incidence has been slowly increasing, with CRUK (2020) reporting a 15% rise over the past decade. In 2015–2017, there were 666 new reported cases in the UK, accounting for less than 1% of all cancer cases.
Penile cancer remains a largely treatable disease, with more than 80% of men presenting with early stage cancer living beyond 5 years (Hakenberg et al, 2018).
Worldwide, the incidence of penile cancer differs between regions, for example, it is markedly higher is some areas of South America, Asia and Africa; in India, the disease accounts for up to 11.6% of malignant diseases in men (Takiar et al, 2014) and, in Paraguay and Uganda, the incidence is 4.2 and 4.4 per 100 000, respectively (Ottenhof et al, 2016a). This significant variation in incidence across the different countries can in most part be attributed to religious practices, such as neonatal circumcision and socioeconomic conditions (Barnholtz-Sloan et al, 2007).
Aetiology
In recent years, a better understanding of the risk factors for penile cancer has developed, although its precise aetiology remains unclear. Essentially, two distinct pathogenic pathways for penile cancer are recognised, with the first relating to high-risk human papilloma virus infection (HPV), and the second to chronic irritation and inflammation, for example, due to lichen sclerosus (LS) (Djajadiningrat et al, 2015).
HPV associated penile cancer
HPV infection is a major risk factor for penile cancer that is contracted through sexual transmission. The HPV subtype that is most commonly associated with penile cancer is the high-risk HPV-16 (Hakenberg et al, 2018), and the HPV-18 subtype has also been widely linked to it (Schlenker et al, 2019).
There is increasing evidence that HPV vaccination in boys would not only prevent penile cancers, but also other oral and anogenital cancers. In addition, it would also help to reduce premalignant genital lesions (Flaherty et al, 2014). Before 2019, only girls were vaccinated against HPV with Gardasil vaccination, but in 2019, this was extended to include boys aged 12-13 years in the UK (Department of Health and Social Care, 2018).
Non-HPV associated penile cancer
The aetiology of LS is unknown; however, irritation (from urine) or infective influences have been highlighted (Bunker and Shim, 2015). On clinical examination, LS is characterised by white patchy areas. It is a progressive disease and, if left untreated, it can cause phimosis and meatal stenosis (Figure 3a) (Ottenhof et al, 2016a). In men, LS mainly affects the foreskin and to a lesser extent the glans penis and the urethra (Ottenhof et al, 2016a).
Risk factors for developing penile cancer have been identified, which logically contribute to either or both pathogenic pathways (Box 1).
Phimosis
The presence of a foreskin is the most important risk factor for the development of penile cancer, and phimosis is strongly associated with the malignancy (Hakenberg et al, 2018). Childhood or adolescent circumcision seems to provide a protection against penile cancer (Larke et al, 2011), because it involves the removal of site susceptible to the development of tumours; however, circumcision in adulthood does not provide any benefit in reducing the risk of developing penile cancer (Hakenberg et al, 2018).
Circumcision not only eradicates the risk of phimosis, but it also helps prevent smegma retention resulting from poor hygiene (Daling et al, 2005). In addition, circumcision appears to reduce the risk of HPV infection (Ottenhof et al, 2016a).
Age
Penile cancer is primarily a disease of the elderly, but it can also affect younger men. The mean age at diagnosis is 66 years (de Sousa et al, 2015).
Psoralen-UV-A photochemotherapy
Men who undergo treatment for psoriasis with psoralen-UV-A photochemotherapy (PUVA) are at increased risk of developing penile cancer, although only a small number of studies have reported this (Hakenberg, et al 2018). As a consequence, it is recommended that these patients should undergo genital examination during follow-up.
Genital warts
The incidence of penile cancer in men who have a history of genital warts (Figure 3b) due to HPV infection has been reported as being 8.2 times higher than that men without such a history (Blomberg et al, 2012).
Clinical presentation
The exophytic nature of the majority of penile cancers should make the diagnosis obvious (Figures 3a-3f). However, when the cancer is not visible because it is hidden by an intractable foreskin or arises from within the distal urethra, it can be more challenging to diagnose.
Patients with an obvious cancer commonly present with a range of symptoms: they usually self-report a lesion or lump on the penis and may have ulceration, redness, soreness and irritation (Turner et al, 2013). In addition, they may experience bleeding, penile pain, difficulty voiding or a foul-smelling discharge from under the foreskin (Alnajjar and Malone, 2016). Other rarer symptoms that can be indicative of more advanced cancer include a lump in the groin (palpable groin node) (CRUK, 2018).
It is surprising that, with the majority of penile lesions being obvious, many men present late, but sadly this is often the case. Reasons include being too embarrassed to seek medical attention and, due to its rarity, non-specialist health professionals may not recognise the seriousness of the situation, resulting in a further delay in definitive treatment (Skeppner et al, 2012).
Patients who present to their primary care team require urgent referral to the urology department. In accordance with suspected cancer referral guidelines, patients should be seen within 14 days of initial referral. Cancer should be either confirmed or excluded within 31 days. For those in whom cancer is confirmed, treatment must commence within 62 days (NHS England, 2019).
Diagnosis
Careful clinical examination of the primary lesion and attention to the presenting history is paramount. When assessing a patient, the healthcare practitioner should provide a detailed description of the lesion (Box 2). Photography can be helpful and aid discussion at multidisciplinary team meetings where treatment is being discussed and decided.
The role of penile biopsy
The basis for the management of any type of cancer is to plan treatment in accordance with the histological findings, and penile cancer is no exception. Therefore, a penile biopsy should be performed to confirm diagnosis (Hakenberg et al, 2018), but in a bid to limit delays in treatment biopsy is not required prior to referral at every specialist penile cancer centre.
It is, however, important to be aware that, although the appearance of penile cancer is clear in the majority of cases, there are some rare alternative presentations. Penile metastasis has been reported from sites such as bladder (Valsero et al, 2013), prostate (Sánchez et al, 2011) and rectum (Nunes et al, 2015). Additionally, inflammatory lesions can occasionally mimic the appearance of a penile cancer (Alnajjar et al, 2016).
Imaging
Primary tumour staging
The current European Association of Urology (EAU) guidelines (Hakenberg et al, 2018) state that imaging of the primary lesion is not necessary for every case, however, magnetic resonance imaging (MRI) with artificial erection using intracavernosal alprostadil injection or ultrasound with Doppler is useful in order to delineate the position and depth of the tumour when organ-sparing surgery is intended (de Vries, 2019).
Lymph node imaging
In patients whose inguinal lymph nodes are impalpable the likelihood of micro-metastatic disease is about 25% (Hakenberg et al, 2018). The ability to accurately investigate (through imaging) the presence or absence of inguinal or pelvic metastasis is difficult. Computerised tomography (CT) can be useful to reduce the possibility of missing lymph nodes in those where palpation is difficult, especially in obese patients; it is also beneficial for identifying large nodes or masses. However, CT is unhelpful in identifying micro-metastases, which ultimately can be determined only through histopathology of surgically excised nodes (Kirkham, 2016).
Imaging of the groin with ultrasound with or without fine needle aspiration (FNA) is more sensitive than CT. It is helpful for staging in patients whose groin nodes are palpable, because if the FNA is positive the patient can proceed directly to inguinal lymphadenectomy (Hakenberg et al, 2018). However, FNA cannot be relied on solely to exclude groin disease in those with impalpable nodes (Kirkham, 2016).
Sentinel node biopsy is a diagnostic surgical procedure that has increasingly become the gold standard for identifying microscopic cancer cells within the inguinal lymph nodes (Hakenberg et al, 2018). The concept is based on the physiology of penile lymphatic drainage that passes first into a sentinel node before spreading into the other inguinal nodes. A negative sentinel node suggests the absence of lymphatic spread and further surgery at that point is not indicated. However, in patients with a positive sentinel node, a completion lymphadenectomy is required (Hakenberg et al, 2018).
Staging and grading
Penile cancer is classified using the tumour, node, metastases (TNM) staging system (Table 3). Staging defines the extent of the cancer involvement in the penis, the degree of lymph nodes affected and assesses for distant metastases. Grading assesses the aggressiveness of the disease, with G1 being low grade and G4 being the highest grade (Brierley et al, 2016).
| Clinical classification | |
|---|---|
| T: primary tumour | |
| TX | Primary tumour cannot be assessed |
| T0 | No evidence of primary tumour |
| Tis | Carcinoma in situ |
| Ta | Non-invasive verrucous carcinoma |
| T1 | Tumour invades sub-epithelial connective tissue |
| T2 | Tumour invades corpus spongiosum with or without invasion of the urethra |
| T3 | Tumour invades corpus cavernosum with or without invasion of the urethra |
| T4 | Tumour invades other adjacent structures |
| N: regional lymph nodes | |
| NX | Regional lymph nodes cannot be assessed |
| N0 | No palpable or visibly enlarged inguinal lymph nodes |
| N1 | Palpable mobile unilateral inguinal lymph node |
| N2 | Palpable mobile multiple or bilateral inguinal lymph nodes |
| N3 | Fixed inguinal nodal mass or pelvic lymphadenopathy, unilateral or bilateral |
| M: distant metastasis | |
| M0 | No distant metastasis |
| M1 | Distant metastasis |
| Pathological classification | |
| The pT categories correspond to the clinical T categories | |
| The pN categories are based upon biopsy or surgical excision | |
| pN: regional lymph nodes | |
| pNX | Regional lymph nodes cannot be assessed |
| pN0 | No regional lymph node metastasis |
| pN1 | Metastasis in one or two inguinal lymph nodes |
| pN2 | Metastasis in more than two unilateral inguinal nodes or bilateral inguinal lymph nodes |
| pN3 | Metastasis in pelvic lymph node(s), unilateral or bilateral extra-nodal or extension of regional lymph node metastasis |
| pM: distant metastasis | |
| pM1 | Distant metastasis microscopically confirmed |
| G: histopathological grading | |
| GX | Grade of differentiation cannot be assessed |
| G1 | Well differentiated |
| G2 | Moderately differentiated |
| G3 | Poorly differentiated |
| G4 | Undifferentiated |
Pathology
Penile cancer develops from premalignant cells known as penile intra-epithelial neoplasia (PeIN) (Figure 3c), which clinically presents as whitish irregular patches on the skin or sharply defined with a red smooth appearance (Chaux et al, 2016).
Because the penis consists of different types of cells, different types of cancer can occur. The majority of tumours (over 95%) are squamous cell carcinomas (SCC), of which there are several recognised subtypes: warty, papillary, basaloid, verrucous and sarcomatoid (Hakenberg et al, 2018). Other non-SCC include sarcomatoid tumours, malignant melanoma, extramammary pagets and malignant lymphomas (Chaux et al, 2016).
Treatment
Surgery is the gold standard treatment for penile cancer and, in more recent years, penile-preserving surgical techniques have evolved with the aim of providing curative treatment with minimal functional and anatomical changes (Hadway et al, 2016).
Radical circumcision is indicated in men with preputial disease, although adequate clearance must be achieved (Hakenberg et al, 2018). Recurrence rates of up to 30% have been reported following circumcision, with the majority of these occurring in the first 2 years following diagnosis (Pietrzak et al, 2004). Therefore, close surveillance after surgery is essential.
Glans resurfacing involves the removal of the glans epithelium together with the subepithelial tissue. The penis is then covered with a split skin graft (Figure 4a) (Hakenberg et al, 2018). This treatment is offered to patients with pre-malignant disease.
Glansectomy involves complete removal of the glans penis, with a skin graft reconstruction (Figure 4b). It is suitable for T2 lesions and does not involve excision of the corpus cavernosum, thus preserving sexual function and adequate penile length (Horenblas et al, 2013).
Partial penectomy is required if there is evidence of involvement of the erectile bodies. Although the surgery is not dissimilar to a glansectomy, after surgery not all patients will have enough penile length to enable voiding while standing nor be able to engage in penetrative sexual intercourse (Branney et al, 2011).
After penile preserving surgery a tie-over dressing will usually remain in situ for several days. Nurses should check the surgical sites/dressings regularly to assess for bleeding or possible infection. Baths and showers should be avoided until the operative dressing has been removed. If a graft has been taken from the thigh, a non-adherent dressing will be applied that will usually remain in place for up to 2 weeks (Orchid, 2019). A urethral catheter will remain in situ until the wounds have sufficiently healed. Men should be instructed on how to clean around the their penis and advised to increase their fluid intake to minimise the risk of urinary tract infection (Orchid, 2019).
Men with T4 or high-grade stage T3 disease require total penectomy with formation of a perineal urethrostomy, whereby the urethra is rerouted and the urethral meatus is located behind the scrotum. Men are informed that they will need to sit down to pass urine following this surgery. It is important that they are also informed about total phallic reconstruction, which allows restoration of both urinary and sexual function, usually by the radial artery forearm flap phalloplasty technique (Garaffa et al, 2016).
Lymph-node management
The lymphatic drainage from the primary penile cancer is to both inguinal regions (Hakenberg et al, 2018). The extent of lymph node involvement is the most important prognostic factor in penile cancer (Djajadiningrat et al, 2014). As previously mentioned, up to 25% of patients who present with impalpable nodes will have micro-metastasis. (Ottenhof et al, 2016b).
The treatment for patients with metastatic lymph nodes is surgical excision. Inguinal lymphadenectomy involves removal of all lymph nodes within the affected groin. This procedure is not without possible complications, with up to 35-70% of patients either experiencing short-or long-term problems, including genital or lower limb lymphoedema, wound breakdown, infection, lymphocele/seroma and necrosis (Ottenhof et al, 2016b). Despite this, the value of performing inguinal lymphadenectomy greatly outweighs any complications associated with the procedure (Hakenberg et al, 2018). Indeed, 80% of patients with one or two nodes positive without extranodal extension will achieve a curative outcome following lymphadenectomy. (Pandey et al, 2006).
Chemotherapy
The EAU guidelines (Hakenberg et al, 2018) recommend that patients with metastatic disease (N2-3) undergo adjuvant chemotherapy after radical lymphadenectomy. This includes three to four cycle of cisplatin, a taxane and 5-fluorouracil or ifosfamide (Hakenberg et al, 2018). More recently, it has been found to have a role in downstaging advanced tumours prior to undergoing surgery (Hadway et al, 2016). However, further research is required before this can become a standard treatment and, as such, chemotherapy is offered on an individual basis only.
Psychological impact
The impact of a cancer diagnosis on the individual and their loved ones can be devastating (Eardley, 2016). For the majority of men, surgery to treat penile cancer is straightforward (Siow et al, 2005). However, the effects on their body image, sexual and urinary function and relationships can be considerable and in some cases can cause long-term distress (Witty et al, 2013). The impact on the individual will vary and will be influenced by factors including their age, whether they are in a relationship and how well they are supported (Eardley, 2016). It is well documented that spouses and loved ones can be invaluable in providing this support (Bullen et al, 2010).
The role of the clinical nurse specialist
The value of the clinical nurse specialist (CNS) role in improving the experiences of those diagnosed with cancer cannot be underestimated (Henry, 2015). Ideally, the relationship of the CNS with the patient and family commences at the time of cancer diagnosis in order offer and provide both psychological and practical support. Until diagnosed, most men have never heard of this rare cancer and even less about the options available to treat it (Bullen et al, 2010). The National Cancer Patient Survey (NCPS) demonstrated that patients who were in contact with a CNS reported a more favourable overall experience than those who did not have such contact on a range of items relating to information, choice and care (Quality Health, 2018).
The CNS can signpost patients to information booklets published by cancer charities, including Orchid that solely focuses on penile, testicular and prostate cancers. In addition to practical support, CNSs are well placed to offer psychological support to patients and carers, which can positively influence the experience and psychological morbidity associated with illness and treatment (Henry, 2015). Referral to a psychologist or counsellor can be offered to help with adjustment to their diagnosis and subsequent treatment.
Conclusion
Penile cancer is a rare disease with a low incidence in Western countries. It is curable, if treated early but it has a poor prognosis in those who present late with advanced metastatic disease. Men who present with symptoms of penile cancer should be referred promptly to a specialist penile cancer treatment centre to confirm or exclude disease. Nurses with an awareness and understanding of this rare cancer can play an integral role in facilitating this process and supporting the patient at the start of their cancer journey. Once cancer has been confirmed, the nurse's role in supporting the patient is essential.