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17
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CASE
Localized penile cancer
Ian Eardley
Expert commentary Ian Eardley
Case history
A 58- year- old married man presented with a 3- month history of a painful ulcerating
lesion on his glans penis. He had initially consulted with his general practitioner who
had treated him with topical antifungal cream. When this failed to provide any benefit,
a urological opinion was sought. The man was otherwise well and he took no regular
medication. On examination he was circumcised and there was a peri- meatal ulcer of
the glans penis with a palpable firm mass within the glans penis approximately 1 cm in
diameter (Figure 17.1). There was no palpable inguinal lymphadenopathy. A staging
penile magnetic resonance imaging (MRI) scan confirmed a small tumour that was
invading the corpus spongiosum of the glans penis but that did not invade the corpora
cavernosa (Figure 17.2). There was no evidence of inguinal lymphadenopathy on the
MRI scan. An incisional penile biopsy, performed under local anaesthesia confirmed a
G3 squamous cell carcinoma (SCC).
Figure 17.1 Squamous cell carcinoma of the penis. There is an ulcerating lesion in the peri- meatal
region. A small firm mass was palpable within the glans penis.
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Figure 17.2 MRI scan of the penis. The MRI shows a plaque of tumour in the peri- meatal region of the
glans penis approximately 10.4 mm in diameter.
Learning point Epidemiology and aetiology of penile cancer
Penile cancer is uncommon in the Western world, where it accounts for <1% of male
cancers. However, there is substantial variation in incidence internationally, such that penile
cancer can account for up to 10% of male cancers in parts of Africa, South Asia, and South
1
America.
The incidence increases with age and risk factors include human papillomavirus (HPV) infection,
lichen sclerosis, phimosis, and smoking.
Circumcision early in life is protective. As such, penile cancer is rarely seen in those cultures that
practise circumcision in the neonatal period or in childhood.
HPV- related tumours account for around half of the clinical cases seen in the UK and are
associated particularly with warty carcinomas and with basaloid carcinomas. The commonest
HPV subtypes are types 16 and 18.
There are a number of premalignant penile lesions. Penile intraepithelial neoplasia (PeIN),
which usually presents as a red patch on the glans or in prepuce will progress to carcinoma
in up to a third of cases. In contrast, although lichen sclerosis and Bowenoid papulosis can
progress to invasive cancer, they do so infrequently. Other conditions that can progress to invasive
cancer include giant condyloma (Buschke– Löwenstein tumour), Bowen’s disease, and Paget’s
disease.
2,3
3– 5
2
Clinical tip Staging of penile cancer
Clinical staging of primary penile cancer is based primarily upon clinical examination. The most
important clinical features to identify are whether there is a phimosis and whether the tumour
clinically involves the corpus spongiosum and/ or the corpus cavernosum. The most commonly used
imaging modalities are ultrasound6 and MRI, with the latter having good sensitivity and specificity for
differentiating invasion of corpus spongiosum from invasion of corpus cavernosum.7 MRI is usually
performed following an artificially induced erection.
The procedure for identifying lymph node involvement depends upon whether there is evidence
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of lymphadenopathy on clinical examination of the groins. If there are no palpable nodes in either
groin then dynamic sentinel node biopsy is the preferred staging technique (see later ‘Learning
point’ box on sentinel node biopsy). If there are palpable nodes, an abdominal pelvic computed
tomography (CT) scan will determine the extent of the nodal involvement in the groins and
the pelvis while an 18- fluorodeoxyglucose (FDG) positron emission tomography/ CT scan can
demonstrate metastatic disease.
The tumour, node, and metastasis (TNM) staging of penile cancer (Table 17.1) was updated in 2016
(published in 2017).
of T2 and T3 tumours, with the former reflecting invasion of the corpus spongiosum and the latter
reflecting invasion of the corpus cavernosum.
Table 17.1 TNM penile cancer staging, 2016
Primary tumour
Tx
T0
Tis
Ta
T1a
T1b
T2
T3
T4
Regional lymph nodes
pNx
pN0
pN1
pN2
pN3
Distant metastases
M0
M1
Histopathological grading
Gx
G1
G2
G3
G4
9,10
Although there were a number of changes, the most notable was a redefinition
Primary tumour cannot be assessed
No evidence of primary tumour
Carcinoma in situ
Non- invasive verrucous carcinoma
Tumour invades subepithelial connective tissue
No lymphovascular invasion and not poorly differentiated
Tumour invades subepithelial connective tissue
Either lymphovascular invasion or poorly differentiated
Tumour invades corpus spongiosum with or without urethral invasion
Tumour invades corpus cavernosum with or without urethral invasion
Tumour invades other adjacent structures
Regional lymph nodes cannot be assessed
No regional nodal metastasis
One or two unilateral inguinal lymph node metastases
More than two unilateral nodal metastasis or bilateral inguinal nodal metastasis
Pelvic nodal metastasis or extracapsular spread of any nodal metastasis
No distant metastasis
Distant metastasis
Grade of differentiation cannot be assessed
Well differentiated
Moderately differentiated
Poorly differentiated
Undifferentiated
8
167Case 17 Localized penile cancer
Following multidisciplinary team review, the patient was counselled regarding treatment options. He wished to maintain as much penile length as possible and wished, if
possible, to remain sexually active. Accordingly, he chose to undergo glansectomy with
split- skin grafting of the corpora cavernosa rather than partial penectomy. Surgery was
undertaken successfully without significant complications. A split- skin graft was taken
from the thigh and fixed to the corporal tips with a tie- over dressing (Figure 17.3). The
dressing remained in place, in conjunction with an indwelling catheter for 1 week.
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Figure 17.3 Post- glansectomy image. Tie- over dressing (soaked in povidone- iodine) following glansectomy
and skin graft with urethral catheter. Both dressing and catheter remain in situ for about 7 days.
Expert comment Rationale for conservative surgery in localized penile cancer
Until the early years of this century, the traditional view was that a clear margin of at least 2 cm
was required to achieve a cure for men with penile cancer. In recent years, it has become clear
that conservative surgery is both effective and safe in the treatment of localized penile cancer, with
a number of recent studies confirming that conservative surgery can achieve safe outcomes with
resection margins of only a few millimetres. Local recurrence rates of 5– 10% are typically reported
following conservative surgery.
Accordingly, circumcision can effectively treat tumours affecting the prepuce while tumours that are
confined to the glans penis (Ta, T1, and T2 tumours) can be treated by glansectomy with skin grafting
of the corporal tips. For patients with small superficial Ta tumours, perhaps associated with penile
intraepithelial neoplasia, glans resurfacing is an option.
More radical surgery is required for more proximal tumours. For tumours invading the corpora
cavernosa a partial penectomy will usually suffice. For more proximal tumours a total penectomy may
be necessary in order to achieve complete tumour resection, combined with a perineal urethrostomy.
In some cases, where the extent of the tumour within the corpora cavernosa is unclear, perioperative
frozen section can be a useful adjunct.
Clinical tip Glansectomy and glans resurfacing technique and outcomes
Glansectomy takes advantage of the plane between the corpora cavernosa and the glans penis. Using
a circumcising incision, it is possible to enter this plane, and to remove the glans penis from the
corporal tips with division of the urethra ventrally. Following spatulation of the urethra the corporal
tips can receive a split- skin graft, usually taken from the thigh. The graft is quilted in place, and fixed
11– 13
with a tie- over dressing that stays in place for around 7 days. Urinary drainage is achieved using an
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indwelling catheter that remains in situ until the glans dressing has been removed. Such surgery can be
performed either as a day case or with overnight stay.
More proximally invading tumours can still benefit from reconstruction providing that the tumour is
confined to the tips of the corporate cavernosa. Excision of the corporal tips in continuity with the
glans can be followed by primary repair of the corpora with skin grafting over the top.
Glans resurfacing involves removal of the skin from the glans penis, usually undertaken in conjunction
with a circumcision. A split skin graft can be used to cover the spongiosal tissue. Spatulation of the
meatus is necessary and the postoperative care is as described for glansectomy.
Expert comment Conservative surgery
The primary purpose of conservative surgery is to maintain penile length and penile function.
Although the functional outcomes of conservative surgery are relatively poorly documented, what
literature is available suggests that the outcomes are good. The cosmetic appearances are reasonable,
and a significant number of men are able to retain sexual function, although there is inevitably
some loss of sensation. Urinary function is retained with full continence, although urinary spraying is
common, such that some men need to sit down in order to pass urine while others use disposable
funnels to hold over the phallus when standing to pass urine, thereby directing the urinary stream.
Histology showed a T2G3 SCC, basaloid type, with negative surgical margins. The
tumour extended to 7 mm from the resection margin.
169Case 17 Localized penile cancer
Learning point Histological types of penile cancer
Penile cancer is almost always a SCC. There are multiple different histological subtypes of penile
cancer. The commonest is the so- called common or usual type of SCC, which accounts for around
50% of cases. Less common types include warty carcinoma (around 10%), verrucous carcinoma
(around 5%), and papillary carcinoma (around 10%), which all tend to have a good prognosis.
Both basaloid (around 5%) and sarcomatoid (around 2%) types have a poor prognosis.
There are multiple rare variants including pseudohyperplastic carcinoma, carcinoma cuniculatum,
pseudoglandular carcinoma, adenosquamous carcinoma, and clear cell carcinoma.
Subsequently, the patient underwent a CT scan of the abdomen and pelvis that
showed no evidence of inguinal nodal disease. He then underwent sentinel lymph
node biopsy to assess the inguinal nodes. Surgery was performed under general anaesthesia as a day case with a single node being obtained from each groin.
Learning point Rationale for lymph node assessment
Penile cancer spreads primarily via the lymphatic system in a stepwise and sequential fashion. From
the midline, penile tumour spread will occur to the inguinal nodes (in both groins) before spreading
further (via the femoral canal) to the pelvic nodes and then on to the para- aortic notes. It is extremely
unusual for tumour to ‘skip” past one set of nodes to a higher set of lymph nodes. Blood- borne
metastasis is also extremely unusual and typically only occurs in late- stage disease.
For patients such as this man, with impalpable inguinal nodes, a number of approaches can be
considered. The likelihood of nodal spread is largely dictated by the stage and grade of the primary
tumour. Overall, around 20– 25% of men with clinically impalpable disease will have micro- metastatic
disease with the greatest risk being in those with poorly differentiated (G3) or invasive (T2 or greater)
disease. Most guidelines have identified these criteria as representing patients with high- risk disease.
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For patients with a low risk of disease (T1 or less, G1 tumours), most guidelines suggest surveillance
combining clinical examination and radiological surveillance.
For patients with high- risk disease (T2 or greater and/ or G3 tumours), a number of approaches have
been advocated. Some advocate bilateral inguinal lymphadenectomy in all high- risk cases (so- called
prophylactic inguinal lymphadenectomy), while others support clinical and radiological surveillance.
The difficulty with surveillance is that current imaging techniques cannot consistently identify disease
in lymph nodes <1 cm in diameter. The difficulty with prophylactic lymphadenectomy is the morbidity
associated with that operation.
For these reasons, a ‘middle way’ using sentinel node biopsy has become generally accepted as the
most appropriate approach for staging impalpable inguinal nodal disease, although there are no
prospective randomized control trials confirming either safety or efficacy.
Learning point Sentinel node biopsy
Sentinel lymph node biopsy relies upon the concept that lymphatic spread occurs in a sequential,
stepwise manner. Using this hypothesis, penile tumours spread from the midline via the lymphatic
channels to a ‘sentinel’ node in each groin. Isolation and examination of this node allows prediction of
whether the rest of the nodes in that groin (or basin) are at risk.
To localize the sentinel node, an intradermal injection of colloid particles labelled with technetium99m is made in the penis to facilitate imaging of the sentinel node on a lymphoscintigram. A few
hours later, under general anaesthetic, a further injection of patent blue dye is made into the penis,
which complements the radioactive colloid injection. Using a Geiger counter, it is possible to explore
both groins to identify radioactive blue sentinel notes. Typically, one or two nodes are found in
each groin.
If the sentinel node shows no evidence of tumour, then it is assumed that there is no tumour spread
in that groin and no further treatment is required. If the sentinel node does show evidence of tumour,
then full inguinal lymphadenectomy is undertaken at a separate operation.
The results of sentinel lymph node biopsy suggest a false- negative rate of 5– 10%.14 The morbidity
of sentinel lymph node biopsy is low with occasional wound infections and occasional small
lymphoceles.
On the right side, histology of the lymph node showed SCC within the node (no
extracapsular spread) while the left side showed no tumour. As a consequence, the
patient subsequently underwent a right inguinal lymphadenectomy from which he
made a recovery complicated by wound infection and persistent lymphatic drainage
with temporary lymphocele formation. There was no additional tumour in the resected
lymph nodes. No further adjuvant treatment was necessary.
Learning point Inguinal lymphadenectomy
Inguinal lymphadenectomy is a morbid surgical procedure that involves removing all the superficial
inguinal and deep inguinal lymph nodes that lie within the femoral triangle. The surgical margins are
the inguinal ligament proximally, the adductor muscles medially, the sartorius muscle laterally, and the
crossover of the sartorius muscle and the adductor longus muscle distally. In most cases such as this, a
modified surgical approach can be taken with preservation of the long saphenous vein.
Despite preservation of the saphenous vein, there is considerable morbidity with wound infection,
lymphoedema, and lymphocele formation all being common. Less frequently, complete wound
breakdown can occur. Significant complications occur in 30% or more of patients.
receive adjuvant radiotherapy, the lymphoedema is typically permanent and severe and in patients
who need to undergo bilateral lymphadenectomy, the oedema can affect the scrotum and penis.
15
15
Indeed, in patients who have undergone a partial penectomy followed by bilateral lymphadenectomy,
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the penile stump can occasionally end up buried within the lymphoedematous scrotum.
Lymphoedema is best managed by massage and compression stockings and, if it affects the
scrotum, by the use of supportive cycling shorts. Surgical treatment is rarely effective. Patients with
lymphoedema are potentially prone to subcutaneous streptococcal infections.
Persistent lymphatic drainage and lymphocele is a common complication that is best treated in the
early stages by use of a perioperative surgical drain. Following drain removal, intermittent aspiration
of the lymphocele, perhaps twice a week, will ultimately lead to resolution, although this may take
several weeks.
In patients with extensive nodal disease (pN2) or with extracapsular spread,16 adjuvant radiotherapy
can be used, although there are no randomized trial data to confirm efficacy.17 While some
advocate prophylactic pelvic node resection in such cases, again, there are no trial data to confirm
benefit.
Following treatment, the patient remained under follow- up for 5 years, with
regular clinical examination and CT scanning. There was no clinical or radiological
evidence of recurrence during that time and he was then discharged. Functionally,
he was able to stand when passing urine with occasional spraying of urine. Erectile
function was maintained despite the glansectomy although there was loss of sensation as a consequence of the skin grafting and accordingly, while he was able to
achieve sexual intercourse with penetration, he did have difficulty in achieving an
orgasm.
171Case 17 Localized penile cancer
Expert comment Minimally
invasive approaches to
lymphadenectomy
One approach to reducing the
morbidity of lymphadenectomy
is to perform the procedure
endoscopically either using
a laparoscope or even using
robotic- assisted techniques.18
By minimizing the size of the
skin incision, the reported
complications appear to be much
less frequent.
19
Expert comment Follow- up and prognosis
The outcome of treatment for men with penile cancer is generally good. The overall cancer- specific
5- year survival rate is around 70– 80% in most modern series. Adverse prognostic features include
tumour histological type, tumour stage, and tumour grade but overall the most important adverse
prognostic feature is the presence of nodal disease at presentation.
Local or regional nodal recurrence typically occurs within 2 years of the primary treatment.
Accordingly, most centres pursue an intensive (3– 4- monthly) follow- up regimen for the first 2 years
with regular clinical examination and regular imaging. Follow- up continues for at least another 3 years,
albeit with a less intensive regimen (6– 12- monthly).
Local recurrence can occur with organ- sparing surgery, and when it does so, is treated by more
aggressive surgical excision of the recurrent tumour. Regional recurrence is often less amenable
to treatment, but if identified early can be treated by radical surgery with or without adjuvant
radiotherapy or chemotherapy.
14
A final word from the expert
Penile cancer is rare in the Western world and it may be that it becomes even less common
in the future with the advent of population immunization programmes against HPV. Modern
management entails initial primary local surgical treatment of the primary tumour with
subsequent nodal staging and treatment as appropriate.
It is now clear that the primary surgery can be conservative with surgical margins of only a
few millimetres being acceptable. This provides for better functional outcomes. In patients
without palpable nodal disease in the groin, sentinel node biopsy has become the mainstay
of nodal staging with relatively low false- negative rates. This has reduced the need for radical
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lymphadenectomy with all its associated morbidity. At present, there is no place for adjuvant
therapy in patients with localized penile cancer.
The outlook for most men with penile cancer is good, with long- term survival being the norm.
Men with inguinal disease at presentation have a less good prognosis and current research is
focused on identifying the role of adjuvant therapy.
References
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features, and human papillomavirus status of 103 patients with penile carcinoma. World J
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173Case 17 Localized penile cancer
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