CARCINOMA OF PENIS

Dr Hitesh Patel
Associate professor
Surgery Department
GMERS Medical College ,Gotri

Introduction
Incidence worldwide is roughly 1% of
the total cancers in male
Social stigma and reluctant patient
delayes the presentation
Early detection can prevent major
morbidity and mortality

Ca Penis

Epidemiology
Risk factor
Pathology
Premalignant lesion & Mx
Investigation and dx
Staging
Mx of local tumor according to stage
Mx of LN
Metastasis
3

Epidemiology
What is the incidence of Ca penis?
1 case per 100 000
~ 0.5 % of all malignancies Western World
(decreasing)
Higher incidence in South America (Brazil), East
Africa and South East Asia (10% of all male

malignancy)
SEER database: no racial difference between
black and white in US
But poor prognostic factor if African American
ethnicity (Rippentrop et al, 2004)
Overall incidence is decreasing
4

Risk factors
What are the risk factors?

1. Smoking
2. UV radiation
3. Foreskin: phimosis , poor hygiene

neonatal circumcision eliminate risk by 5x [Daling 2005]

But not circumcision in adult (Maden 1993)

4. HPV infection (16, 18): asso in 50%

Sexual transmission causing genital warts, condyloma

acuminate
HPV infects the basal epithelial cell that proliferates
Daling (2005) HPV DNA was detected in 80 % of tumor
specimens
Carcinogenesis : interfering with p53 & pRB
Role in prognosis is unclear
Verrucous carcinoma is not related to HPV infection

5. Penile trauma

Prognostic makers:

. p53, SCC antigen, P16, Ki-67m E-cadherin and MMP-2

7

Pathology

SCC (95%)
1.
2.
3.
4.
5.
6.

Usual type (60-70%)

Papillary (7%)
Condylomatous (7%)
Verrucous (7%)
Basaloid (4%)
Sarcomatoid (4%)

Malignant Melanoma (2%)

Basal cell carcinoma (2%)
Extra-mammary Pagets disease (adenoCa from
penile skin)
Sarcoma
8

What are the growth patterns and

differentiation grading systems?

What is Broders & Maiche

classification?
Broders grading :Divided into 4 grade (1921)
Define the level of differentiation based on

Keratinization
Nuclear pleomorphism
Number of mitosis
+ other factors

80 % of the Ca penis is low grade lesion ( Gd 1 and 2 )

20% Gd 3 and 4

Maiche grading : divided into 3 grade

Maiche 1991

Correlate with 5 year survival

Grade 1
80%
Grade 2,3
50%
Grade 4
30%
10

What is the distribution of Ca penis?

Glans (50%)
Prepuce (21%)
May be related to constant exposure to
irritants within the prepuce

Glans and prepuce (9%)

Coronal sulcus (6%)
Shaft (less than 2%)

11

Risk factor for metastasis

1. Growth pattern

(Cubilla 1993)

Superficiallly spreading, LN met in 42%

Vertical growth, LN met in 82%

2. Basaloid and sarcomatous

histologic pattern [MSKCC review (Cubilla
2001)]

3. Stage
4. Grade
5. Status of vascular invasion

(Slaton 2001)
12

CLINICAL PRESENTATION
Middle aged male with or without a
precancerous condition
Most patients present with mass and
ulceration and / or induration
50% patients have inguinal
adenopathy at initial presentation

How do they present ?

Presentation:
a sore that has failed to heal
a subtle induration in the skin, to a large exophytic growth.
a phimosis may obscures the tumor and allows it to grow undetected.
Rarely, a mass, ulceration, suppuration, or hemorrhage may manifest
in the inguinal area because of nodal metastases.
Pain is infrequent.

Buck fascia, which surrounds the corpora, acts as a temporary

barrier.
Eventually, the cancer penetrates the Buck fascia and the tunica
albuginea, where the cancer has access to the vasculature and
systemic spread is possible
Delay presentation (50%) due to

Embarrassment, guilt, fear, ignorance, and neglect

Self treatment with various skin creams and lotions.
Doctor: confuse with other benign penile lesions

Metastasis :

Dehydration : hypecalcemia in 20% on presentation (PTH like)

[MSKCC]
SOB
14

Natural History
Begins as small lesion, papillary &
exophytic or flat & ulcerative.
Flat & ulcerative lesions >5cm and
extending >75% of the shaft have higher
incidence of metastasis and poor survival.
Pattern in lymphatic spread.
Metastatic nodes cause erosion into
vessels, skin necrosis & chronic infection.
Distant metastasis uncommon 1 10%
Death within 2 years for most untreated
cases.
15

Premalignant lesions

16

What are the premalignant lesions?

17

Cutaneous horn:

extreme hyperkeratosis with base malignant txn with wide

local excision

Pseudo-epitheliomatous micaceous and keratotic balanitis

(PEMKB)
Unusual hyperkeratotic gorwth of the glans
Txn: Excision , may recur

Leukoplakia:

Whitish glanular plaque involve meatus

Asso with CIS
Txn: Excision and FU

Bowenoid papulosis have high risk of progression to SCC

(90% long term)

Giant condyloma acuminata or Buschke-Lwenstein

tumor

Displaces, invades, and destroys adjacent structures by

compression, whereas the standard condyloma remains
superficial and never invades
Does not metastasis

18

Premalignant lesion: CIS

Erythroplasia of Queyrat: [non keratinising CIS]

CIS: as oppose to Bowens disease, occur in glans or inner part of

prepuce
Red velvety circumscribed painless lesion , may ulcerate and painful
Histology:

Atypical hyperplastic mucosal cell with malignant features

Hyperchromatic nuclei & multi-level mitotic figures
Submucosa : proliferation of capillaries & inflammatory infiltrate of plasma
cell

10x more likely to progress then Bowens disease

Treatment
Penile preserving:

Topical 5-FU or imiquimod

5-FU: block DNA synthesis (structure similar to thymine) SE: erythema , weeping
5% Imiquimod (imidazoguinonin tetracyclicamine): induce IF-alfa

Laser (CO2) , photodynamic therapy , cryotherapy , Mohs MS

If affect large area or recurrence: Total glans resurfacing + skin graft +
deep biopsy

High risk of local recurrence in penile preserving txn

Bowens disease: [Keratinising CIS ]

CIS in the genital and perineal skin
Txn : WLE , laser, cryoablation

19

Balanitis Xerotica Obliterans (BXO)

Lichen sclerosis et atrophicus
>10% asso with future Ca penis
Location: White patch on Glans and prepuce, may affect
meatus or fossa navicularis
Aetiology: Infection/ chronic antigenic stimulation,
phimosis
Histology :
1.
2.
3.
4.
5.

epidermal atrophy,
loss of rete pegs,
chronic inflammatory change,
hyperkeratosis with collagenized dermis
perivascular infiltration of dermis

Treatment:

. Steroid cream 4-6/52 for mild scarring and retractable

foreskin
. Surgical excision (circumcision), reconstruct if stricture.
. Remember not to use genital skin for reconstruction
(recurrence)

If still not responsive > biopsy to rule out other causes

like erythroplasia of Queyrat
Koebner phenomenon: BXO recur on split skin graft

20

DIAGNOSING Ca PENIS
Histology forms the cornerstone of
diagnosis
Incisional biopsy of the lesion is the
preferred modality
Biopsy provides opportunity to grade
the tumor at the time of initial
diagnosis

History

Age
Previous duration of phimosis
LUTS
Smoking history
Sexual history: HPV infection
Exposure to UV radiation

22

PE

23

IMAGING MODALITIES
Recommended for :
Staging the disease
Follow up of patient
To assess spread and resectability

IMAGING MODALITIES
USG:
To assess extent and resectability of T4
disease
Assessment of lymph nodes

CT SCAN:
Assessment of lymph nodes
Limited utility in primary lesion

MRI:
Most accurate in detecting primary and
nodal disease

IMAGING MODALITIES
FLUOROSCENCE STUDIES:
For accurate planning of treatment plan
for laser ablation

Lymphoscintigraphy:
Most accurate in identifying need of LN
dissection

Penile biopsy
The most important diagnostic test
Circumcision and excisional biopsy if the
cancer is small
Incisional biopsy should contain tissue
beneath and beside the tumor in order to
help stage the disease

Confirm histological diagnosis

Determine the depth of invasion
Detect the presence of vascular invasion
Evaluate the grading of the tumour ( Broders
classification )
27

How would you stage the

tumor?

Local staging
1. USG, 7.5 MHz
Tumor appear as hypoechoic
Adv : detect corpus cavernosal invasion with sensitivity of
100 %

Disadv: Could not differentiate Ta from T1

2. MRI penis with intracavernosal
prostaglandin
Accurate in demonstrating invasion of the
corpora, and the extent of the cancer
3. CT:
Not useful in local tumour staging because of
poor soft tissue resolution
For LN status
28

STAGING Ca PENIS:
JACKSONS SYSTEM
Jackson classification for SCC of the penis
Stage I - Tumor confined to the glans or the
prepuce
Stage II - Invasion into the shaft or the corpora;
no nodal or distant metastases
Stage III - Tumor confined to the penis;
operable metastases of the inguinal nodes
Stage IV - Tumor involves adjacent structures;
inoperable inguinal nodes and/or distant
metastasis or metastases

STAGING Ca PENIS:
TNM SYSTEM

Tumor

Tis - Carcinoma in situ (Bowen disease, erythroplasia of Queyra

Ta - Noninvasive verrucous carcinoma
T1 - Tumor invading the subepithelial connective tissue
T2 - Tumor invading the corpus spongiosum or cavernosum
T3 - Tumor invading urethra or prostate
T4 - Tumor invading other adjacent structures

Node

N1 - Involvement of a single superficial inguinal node

N2 - Involvement of multiple or bilateral superficial inguinal no
N3 - Involvement of deep inguinal or pelvic nodes, unilateral or

Metastasis

M1 - Distant metastasis present

M1a - Occult metastasis (biochemical and/or other tests)
M1b - Single metastasis in a single organ
M1c - Multiple metastasis in a single organ
M1d - Metastasis in multiple organ sites

STAGING Ca PENIS:
INVESTIGATIONS

Biopsy

Depth of invasion
Histological grading

USG abdomen

Assessment of lymph nodes

Detectable metastases

CT Scan

Lymph nodes
Metastases

MRI

OTHER INVESTIGATIONS
Routine blood investigations:
Anaemia
Raised ESR
Leucocytosis

CXR
Others depending on metastatic
suspicion

INVESTIGATIONS FOR METASTATIC

DISEASE
CXR / CT Scan chest
LFT
CT Head
Bone scan

LNs staging

34

What is the lymphatic drainage of

penis?
First to the inguinal LN and then to the
pelvic LN
Bilateral drainage of the penis to the LN
The inguinal LN

Superficial group that lie deep to the Scarpas

fascia but superficial to the fascia lata (8-25
LNs)
The deep group (deep to the fascia lata) is a
smaller group that lie around the junction of
the long saphenous and femoral veins

The commonest detected group of LN

which include the LN of cloquet lies
cranimedial to the junction between the
long saphenous and femoral veins

35

What is the accuracy of P/E of

lymadenopathy?
High (90%) sensitivity but a low specificity
(20%) of clinical examination detecting
pathologically positive inguinal
lymphadenopathy
50% of patients with penile cancer will
have clinically palpable inguinal LN at
presentation
50% of patients with pathologically
positive unilateral inguinal LN will have
contralateral metastatic disease
36

What is the imaging investigation

for LN?
CT / MRI
Predict LN involvement by size only
Sensitivity : 35 %, specificity : 100 %

Strongest predictor for survival is the

presence or absence of nodal
metastases

37

TREATMENT OPTIONS
SURGICAL TREATMENT
MINIMALY INVASIVE SURGERY
LASER THERAPY
RADIOTHERAPY
CHEMOTHERAPY

SURGICAL TREATMENT OF
PRIMARY DISEASE
Surgery forms the cornerstone of
therapy
Length of healthy stump is the
most important determinant in
deciding the extent of resection
Urinary diversion (Perineal
Urethrostomy) should accompany
total amputation

What are options of organ preserving therapy?

Circumcision
Small tumors confined to the prepuce
But with recurrence 40%
Local wedge excision
Margin of 5 mm
50% recurrence rate
Glansectomy : T1 (not involving the CC)
Tourniquet control
subcoronal incision down to Bucks fascia
proximal margin at least 5mm
the glans cap is mobilized off the head of the corpora
cavernosa
Urethra is transected and split and fixed
Shaft skin is anchored to the new corona
Raw surface is covered with partial thickness skin graft
T1G3 - lowest recurrence rate of 2%
40

SURGICAL TREATMENT OF
PRIMARY DISEASE

What is organ preserving therapy?

Laser surgery

For local and limited invasive disease

Four types of lasers have been used
1.
2.
3.
4.

The carbon dioxide laser

.
.
.

vaporizes tissue
penetrates only to a depth of 1mm
coagulate blood vessels less than 0.5 mm

The ND:YAG laser

.
.

Carbon dioxide
Neodymium:yttrium-aluminum-garnet (ND:YAG)
Argon
Potassium-titanyl-phosphate (KTP) lasers

penetrate 5 mm depending on the power

Can coagulate vessels up to 5 mm

The argon and KTP lasers have less tissue penetration

than the carbon dioxide laser and are rarely used
Result : 7% recurrence in 4yr FU [Frimberger 2002]
42

What are the problems of

conservative treatment?
Not be suitable in cases of multifocal
lesions
Mohs micrographic surgery,
photodynamic and topical therapy
with 5-fluorouracil ( 5-FU) or 5%
imiquimod cream have been
reported for superficial lesions with
relatively high recurrence rate
Best results are achieved with laser
surgery

43

What is Partial penectomy?

When the cancer involves the glans and distal shaft

T1a to T2 (not for T3 !!!!)
Traditionally, partial amputation has required removal of 2-cm
tumour-free margins, to lower risk of local recurrence T (50%
reduced to 6%)
Pathological confirmation a surgical margin of 5-10 mm is safe
Frozen sections at the time of surgery are often helpful, and a
careful review of the specimen and permanent sections with the
pathologist help to determine if the resection has been adequate
If margin + ve: local recurrence in 10%
Patient should be counsell about poor cosmetic and functional result
He will need to sit to void
He cannot have sexual intercourse

If surgical resection by either wedge or partial penectomy does not

provide an adequate margin, a total penectomy should be
considered
If the amount of residual penis and urethra is inadequate to allow
the patient to urinate while standing, a perineal urethrostomy can
be performed

Berry suggested to have 3cm penile functioning length and 2cm clear margin
before consideration of partial penectomy

Recurrence of partial or total penectomy: 0-8%

44

What is total Penectomy ?

Total amputation of penis + excision
of scrotum and its content
Formation of perineal urethrostomy
Complication:
Urethral meatal stenosis

45

 CIS, Ta-1 G1-2 (i.e T1a)

Penis-preserving strategy for those guarantee regular FU
(70%)
local excision + reconstructive syrgery / glansectomy
(depend on size and location of tumor)
Laser , cryoablation, RT & brachytherapy
Mohs MS or photodynamic therapy for (CIS, TaG1)
Local 5-FU (for CIS only)

No difference in local recurrence rate between

micrographic surgery, EBRT, insterstitial brachy and
laser
Overall recurrence 15-20%
Partial amputation for those who dont comply with
regular FU.

T1b G3, T2 (glans only)

V. carefully selected patients with tumour less than half
of glans & close FU can be carried out conservative
strategy
Glansectomy +/- Tip amputation or reconstruction
46
Margin 3mm is consider safe

 T2 (invasion to corpora)
Partial amputation
Margin 5-10mm
If no LN on presenstation 5yr survival 66%

T3 (invasion to urethra)
Total amputation with perineal urethrostomy

T4 (invasion to other structure)

Neo-adj chemo + surgery in responsive patient
(selected)
Others: RT

Local disease recurrence

2nd conservative procedure if < T2
If large or deep infiltrating recurrence partial / total
amputation
External beam radiotherapy / brachytherapy for lesions < 4cm47

What are treatment strategies for

penile cancer?

48

What are treatment strategies for

penile cancer?

49

INDICATIONS OF LYMPH NODE

DISSECTION
All patients with palpable non
responding adenopathy
All patients with cytologically proven
disease
All patients with T2 disease or more
should undergo prophylactic dissection
Minimum dissection is bilateral
superficial inguinal group dissection

MANAGEMENT OF NODAL
DISEASE
Bilateral superficial inguinal node
dissection is the treatment of choice
Deep nodes to dissected on the side
where the superficial nodes are positive
Iliac nodes to be dissected if deep
nodes are positive
Para-aortic adenopathy contraindicates
lymph node dissection

LYMPH NODE DISSECTION: COMPLICATIONS

AND CONTRAINDICATIONS

COMPLICATIONS:

Lower limb lymphoedema

Flap necrosis
Seroma
Infections

CONTRAINDICATIONS

Para-aortic lymphadenopathy
Verrucous carcinoma
Metastatic disease
Major surgery contraindicated

ROLE OF RADIOTHERAPY
INDICATIONS:

Small exophytic lesion if patient does not

want surgery
Inguinal node irradiation if surgery is not
planned

External beam irradiation or mould may

be used
Circumcision should be done prior to
radiation
Stenosis and fistula are the major
complications

ROLE OF CHEMOTHERAPY
Topical 5 FU may be used for very
superficial lesions
Systemic chemotherapy (VBM) has
limited role after node dissection
to prevent metastases
Neo adjuvant therapy is being
investigated for advanced lesions
with unresectable or fixed nodes

CONCLUSION
Surgery is the mainstay of treatment of
carcinoma penis
Histological confirmation is the easiest
and most effective mode of diagnosis
Nodal dissection improves survival and
is hence indicated
Chemotherapy and radiotherapy have
limited indications
Penile reconstructive procedures may
be offered to young males with good