CARCINOMA PENIS

MODERATOR: DR VIMAL YADAV

PRESENTOR: DR SAMRAT SHRESTHA
 Embroyology
• 3rd week of development-mesenchyme cells originating from
primitive streak migrate around cloacal membrane
• Form a pair of elevated Cloacal folds.
• Cranial to the cloacal membrane, the folds unite
to form genital tubercle.
• Caudally: urethral folds anteriorly and anal folds posteriorly .
• Pair of elevations,Genital swellings on each side of the urethral folds
—>scrotal swellings in the male
• Rapid elongation of genital tubercle- now phallus.
• During elongation, phallus pulls urethral folds
forward-form lateral walls of urethral groove.
• Groove extends along ventral aspect of elongated
phallus but does not reach glans.
• Epithelial lining of the groove, which originates in the
endoderm, forms the urethral plate.
• At the end of the 3rd month,2 urethral folds close
over urethral plate, form penile urethra.
 PENIS PARTS:
• ROOT
• SHAFT/BODY
• GLANS
• PREPUCE
 ANATOMY OF PENIS
• ROOT- attached­in­the­perineum
• SHAFT:Free,­pendulous­body-completely­enveloped­in­skin
• Penile­shaft­contains ­3 erectile­columns­–­the­paired­corpora­
cavernosa­and­the­corpus­spongiosum
• Distal­end­of­penis,­­corpus­spongiosum­again­enlarges­
and­assumes­a­bulbous­shape-glans­penis
• Erectile­tissue,­enclosed­within­a­dense­fibroelastic­sheath­of­
connective­tissue,­the­tunica­albugine
SKIN OF PENILE SHAFT
• Thin highly­elastic­and­devoid­of­appendages
• Exception­-smegma producing ­glands ­located­at ­base­of­­corona.
• Devoid­of­fat­and­quite­mobile­because­of­loose­attachments­
between ­dartos ­fascia­and ­underlying ­Buck’s ­fascia.
• Skin ­of­­glans-immobile-direct­attachment­to ­underlying ­tunica­
albuginea.­
• Blood­supply ­to ­penile­skin- External­pudendal­branches­of­the­
femoral­vessels.
• Superficial­penile­fascia(DARTOS)-Devoid­of­fat,­and­consists­of­
loose­connective­tissue­interspersed­by­fibres­of­­dartos­muscle­
from­­scrotum.­
• Deep­penile­fascia(BUCK’S):Denser­fascial­sheath-envelops­both­
corpora ­cavernosa­& ­splits ­to ­envelop­­corpus­spongiosum­
• Distally,­it ­blends­with­tunica­albuginea­covering­all­3 corporal ­
bodies.­
• Proximally,­it­is ­continuous ­with ­dartos ­muscle­and ­deep­perineal­
fascia.­
• Bleeding­from­a­tear ­in ­corporal ­bodies ­is ­usually ­contained­within­
Buck’s­fascia,­and ­ecchymosis­is­limited­to­penile­shaft.
1. Arteries to corporal­bodies-
• Internal ­pudendal­artery(IPA), branch­of­internal­iliac­.
• As­it­emerges­from­Alcock’s­canal,­IPA gives­off­the­perineal­artery,­to
­supply ­ischiocavernosus­and ­bulbospongiosus,­and­­posterior­
surface ­of ­scrotum.
2. Common­penile­artery­- 3 main­branches:­
A. Bulbourethral­artery,
B. Dorsal­penile­artery­
C. Cavernous­(deep,­cavernosal)­artery­
• Common­penile­artery ­that­supplies ­deep ­structures­of­­penis.
 VENOUS DRAINAGE
 Superficial­veins-
• Drains ­penile s­ haft, ­skin ­and ­prepuce
• Drains­into ­great­saphenous­vein ­via­­superficial­external­pudendal­
veins.

 Intermediate ­drainage­system: Drains glans,­corpus­spongiosum­

and­distal­2/3rd of­penis.­

 Deep­venous­drainage­Drain proximal­third­of­penis.­
• Drains­into ­internal­pudendal­vein.
 Lymphatic drainage
 Superficial­inguinal­nodes: Penile­and ­perineal­skin

 Deep ­inguinal­and External ­iliac­nodes: Lymphatics from­­glans­

penis

 Internal­iliac­nodes: ­Erectile­tissue­and­penile­urethra
 NERVE SUPPLY

 D
­ orsal­nerve-division­of­Pudendal­nerve
• Suppy Glans­penis

 S
­ mall ­branches­from­­perineal­nerve- innervation­to­the­skin­on­the­
ventrum­of ­penis,­as ­far ­distally­as ­glans.

 Sympathetic­and­parasympathetic
• ­Pelvic­plexus Deep cavernosal nerve- Supply ­corpora­cavernosa
 First­4 sacral­segmentsTravels­via­Pelvic­splanchnic­nerves­(nervi­
erigentes) Pelvic­plexus PNS to penis(Excitatory)
• Parasympathetic­stimulation­produces­vasodilation

 1
­ 1th and­12th Thoracic &­1st­lumbar­segments descends to­Pelvic­
plexus Sympathetic ­input­to­­penis­(inhibitory).
• Sympathetic­innervation­causes­vasoconstriction,­contraction­of­the­
seminal­vesicles­and­prostate,­and­seminal­emission

­.
PREMALIGNANT LESION
 PEIN
• Carcinoma in situ of the penis (penile intraepithelial neoplasia, also
known as PEIN or PIN)-first description by Queyrat in 1911
• Red cutaneous patch on the penis
• Erythroplasia of Queyrat- PEIN of glans
• Bowen’s disease- PEIN of shaft of the penis
• Diagnosis- Biopsy
• Treatment: Topical 5-FU cream, CO2 laser ablation or surgical
excision.
 Erythroplasia of Queyrat
 Red, velvety, well-marginated lesion of
glans penis;less frequently, the prepuce
 May ulcerate
 Discharge and pain.
 HPE: Normal mucosa is replaced by
atypical hyperplastic cells characterized
by disorientation, vacuolation, multiple
hyperchromatic nuclei & mitotic figures
 Progression to invasive carcinoma in
10% to 33%
 BOWENS DISEASE
 Plaques of scaly erythema
on penile shaft.
 Crusted or ulcerated variants
can occur.
 DDX-BP, nummular eczema,
psoriasis, and superficial BCC
 Untreated—>invasive
carcinoma may arise in about 5%
Treatment:
 Lesions of foreskin- circumcision or excision with a 5-mm margin is
adequate for local control.
 Lesions on glans penis
• Technique:Glans resurfacing
1. Epithelium and subepithelial tissue of the glans penis are
completely dissected off underlying spongiosal tissue.
2. Resulting defect is then closed with a skin graft.

 Topical 5-FU cream, 5% imiquimod cream and ablation with Nd:YAG

potassium titanyl phosphate (KTP) 532-nm, or CO2 lasers
 PENILE CARCINOMA
 Accounts for 0.4% to
0.6% of all malignant
neoplasms among men
in US and Europe
 Up to 10% of malignant
neoplasms in men in
some Asian, African,and
South American Countries
 Disease of older men
 Abrupt increase in incidence
in the 5th -7th decade of life
 ETIOLOGY
• Smoking
• HPV types 16 and 18
• Chronic irritative effects of smegma
• Phimosis
• Chronic balanoposthitis -precarcinomatous states
• Leucoplakia of the glans
• Genital warts
• Penile intraepithelial neoplasia (PeIN)
• Penile Trauma
• Lichen sclerosus (Balanitis xerotica obliterans)
 PREVENTION
 Routine neonatal circumcision
• Circumcision soon after birth confers immunity against CA penis.
• Later circumcision does not seem to have same benefit.

 Avoidance of HPV infection

 Avoidance of tobacco products.

 Prophylactic HPV vaccines are available

• HPV 16/18 vaccine Cervarix
• Quadrivalent HPV 16/18/6/11 vaccine Gardasil
• Gardasil 9 HPV 16/18/6/11/31/33/45/52/58
 CLINICAL PRESENTATION
• Papule, pustule, warty growth OR exophytic lesion
• Shallow erosion or as a deeply excavated ulcer with elevated or
rolled-in edges.
• Erosion through the prepuce, foul odor, and discharge with or
without bleeding.
• Rarely, a mass, ulceration, suppuration, or hemorrhage in the
inguinal area by nodal metastases from a lesion concealed within a
phimotic foreskin.
• RARELY: Urinary retention or urethral fistula from local corporeal
involvement
 Common Location
 Glans (48%)
 Prepuce (21%)
 Glans and prepuce (9%)
 Coronal sulcus (6%)
 Shaft (<2%)
 SYMPTOMS
• Pain does not develop in proportion to the extent of the local
destructive process
• Weakness
• Weight loss
• Fatigue
• Systemic malaise occur secondary to chronic suppuration.
 DIAGNOSIS
• EXAMINATION
• ACESSEMENT with regard to size, location, fixation, and
involvement of the corporeal bodies.
• Inspection of the base of the penis and scrotum-To rule out
extension.
• Rectal and bimanual examination for perineal body involvement and
presence of a pelvic mass.
• Careful bilateral palpation of the inguinal area for adenopathy is
extremely important
 BIOPSY
• Confirmation of the diagnosis
• Assessment of the depth of invasion, the presence of vascular
invasion, and the histologic grade of the lesion
• Classified the histologic types:
1. SCC 48-65%
2. Papillary 5-15%
3. Mixed Carcinoma 9-10%
4. Warty (condylomatous) 7-10%
5. Basaloid 4-10%
6. Verrucous 3-8%
7. Sarcomatoid 1-3%
 SCC - Graded using Broders classification
 Define - Level of differentiation on the basis of keratinization,
nuclear pleomorphism, number of mitoses
1. Low-grade lesions (grade 1 and grade 2):
• Well-differentiated
• Cords of atypical squamous cells projecting downward from a
hyperkeratotic epidermis.
• Lower-grade carcinomas typically demonstrate keratin, prominent
intercellular bridges, and keratin pearls, characteristics that are
absent in high-grade tumors.
2.High grade-poorly differentiated (grade 3 and grade 4)- tumors
originating in the shaft
 Laboratory Studies
• Laboratory tests- often normal.
• Anemia
• Leukocytosis
• Hypoalbuminemia-if chronic illness
• Malnutrition.
• Azotemia: secondary to urethral or ureteral obstruction
• Hypercalcemia without detectable osseous metastases
• PTH and related substances may be produced by tumor and
metastases that activate osteoclastic bone resorption.
 Radiologic Studies
 Penile USG:
• Invariably hypoechoic
• Tunica albuginea separating the corpus cavernosum from the glans-
easily identified : sensitivity for detecting corpus cavernosum
invasion was 100%
 MRI
• Technique of artificial erection (by intracorporeal injection of
prostaglandin E1)
• Augment the use of contrast-enhanced MRI in staging of the
primary tumor.
• Lesions thought to invade the corpus cavernosum, contrast-
enhanced MRI may provide unique information,
•
• CT and lymphangiography offer no useful additional information
over physical examination, especially in patients with no palpable
adenopathy.
• SCC was shown to take up the fluorodeoxyglucose (FDG) and to
be amenable to detection using combination PET and CT
• Physical examination of inguinal region-Clinical gold standard for
evaluating the presence of metastasis.
 METASTASIS
• Most common metastatic sites are the lung, bone, and liver.
STAGING
 SURGICAL MANAGEMENT
 ORGAN PRESERVING
 GOAL
– TO PRESERVE GLANS SENSATION
– TO MAXIMIZE PENILE SHAFT LENGTH

 INDICATION
1. Penile primary tumors exhibiting favorable histologic features
2. Stages Tis, Ta, T1; grade 1 and grade 2
 CIRCUMCISION AND LIMITED EXCISION
STRATEGIES
• Surgical management of carcinoma in situ of glans penis is glans
resurfacing, AKA glans stripping
• 2-cm surgical margin is required for all patients undergoing partial
penectomy.
• Maximum proximal histologic extent of 5mm for Grade 1& 2 and 10
mm for grade 3 tumors.
• LIMITATIONS
1. Proximal and distal deeply invasive tumor
2. High grade tumor
3. skip lesion

• Recurrence rate is 4-6%

 Mohs Micrographic Surgery
• For penile CIS and small, superficially invasive tumors
• Involves layer-by-layer complete excision of the penile lesion in
multiple sessions, with microscopic examination of the undersurface
of each layer.
• Sequential microscopic guidance offers improved precision and
control of negative margin while maximizing organ preservation
 Laser Ablation
 4 most widely used laser energy sources are
1. CO2 Argon
2. Nd:YAGB: M/C used
3. KTP lasers
 PENILE AMPUTATION
 For deeply invasive or high-grade cancers.
 INDICATION
1. Tumors of size 4 cm or more
2. Grade 3 lesions,
3. Invading deeply into glans, urethra or corpora cavernosa.
 PARTIAL PENECTOMY
• M/C for treatment of primary tumor in patients with invasive SCC
• Initially -Amputation of penis at least 2 cm proximal to the tumor-
now no longer mandatory.
• Goals: Preserve ability to void in a standing position and possibly to
allow sexual function
• Urethral stump is created 1-2cm longer than corporal stump to
create neourethral meatus.
• 10-mm clearance is adequate for grade 1 and 2 lesions
• 15 mm for grade 3 tumour.
 TOTAL PENECTOMY
• Misnomer
• Penis is amputated at or near level of suspensory ligament of penis
without removal of corpora cavernosa more proximally.
• Indicated in penile tumors whose size or location would not allow
excision with an adequate surgical margin and preservation of a
remnant sufficient for upright voiding.
 COMPLICATION
 Local recurrence rate after partial or total penectomy 0% to 8%
 COMPLICATIONS
1. Urethral metal stenosis
2. Inability to void in upright position
3. Inadequate sexual function
 v

 URETHRAL FLAP GLANULOPLASTY PERFORMED IN CASE OF URETHRAL

STENOSIS AFTER PARTIAL PENECTOMY.
A. Suprapubic catheter insertion due to urethral meatal stenosis after primary partial
penectomy.
B. Urethral dissection and mobilization up to penoscrotal junction
C. Ventral urethral spatulation and advancement over corpora cavernosa
D. Tension-free suture of urethral flap to tunica albuginea.
E. Suture of urethral flap to skin and 18Fr urethral catheter permanence during 72 hrs to
keep area dry.
 SENTINAL LYMPH NODE
BIOPSY
• Penile cancer only very rarely presents distant metastasis without
prior dissemination via the lymphatic vessels to the inguinal regions.
• Because of this characteristic, Penile CA was an ideal model
disease for the development of sentinel lymph node concept
 TREATMENT OF THE
INGUINAL NODES
• Metastasis to inguinal region are most important prognostic factors
for survival
• Lymphadenectomy alone can be curative.
• Biology of squamous penile cancer is such that it exhibits a
prolonged loco regional phase before distant dissemination,
providing a rationale for the therapeutic value of lymphadenectomy
 European Association of Urology (EAU) and the National
Comprehensive Cancer Network (NCCN) penile cancer guidelines
recommend Pelvic LND in patient with >=2 positive LN or
extracapsular extension in any inguinal lymph node.

 Bilateral PLND is required only if bilateral inguinal nodes are

involved.
• PLND entails removal of obturator, external iliac and internal
iliac nodes
• Anatomical extent is bounded by
1. Inguinal ligament distally
2. Iliac bifurcation proximally
3. Obturator nerve medially
4. Ilioinguinal nerve laterally.
 RADIATION THERAPY
 External-Beam Radiotherapy
1. Primary external-beam radiotherapy affords at least a 50% chance
to control the primary tumor and avoid penile amputation
2. Minimum tumor dose should be at least 66 Gy in 2-Gy fractions
over a period of 6.5 weeks (45 days)

 Brachytherapy:
• Isotope iridium-192
• Temporary implantation of interstitial needles in a parallel array
through and around the tumor
• manually loaded with iridium-192 wire or seeds to deliver a classic
low-dose rate (LDR; 50–60 cGy/h) treatment
• Radiation therapy is ideal for patients with T1 and T2 primary
cancers of the penis.
• Pre-operative RT is useful for patients with mobile lymph nodes ≥4
cm in size in the groin.
• RT provides effective palliation in patients with advanced regional
disease and/or distant metastases.
• Palliative RT useful in alleviating pain from bony mets or inguinal
nodal mass
 CHEMOTHERAPY
INDICATIONS
1. Advanced penile cancer presenting as either bulky or unresectable
regional disease
2. Visceral metastases
3. Disease recurrence

 Single-Agent Chemotherapy(BMP):
1. Low-dose (50 mg/m2) cisplatin
2. Bleomycin
3. Methotrexate
 COMBINATION THERAPY
• Fluorouracil + Cisplatin
• Paclitaxel+Ifosfamide+Cisplatin
• Irinotecan+Cisplatin
• Docetaxel+Cisplatin+Fluorouracil

 ADJUVANT THERAPY
• Combination VBM Vincristine, Bleomycin, and Methotrexate therapy
was administered in 12 weekly courses
• Neoadjuvant chemotherapy-valuable treatment option for patients
with irresectable penile carcinoma, which is otherwise considered
incurable.
• Surgery should be performed only in patients showing clinical
response to chemotherapy
• Prognosis for nonresponding patients who underwent surgery was
dismal and local control was not improved.
 TARGETED THERAPY

• Second-line treatment in metastatic penile cancer

• Majority cases of penile SCC are associated with over-expression of
EGFR and loss of expression of RASSF1A, a potential tumor
suppressor
• EGFR expression in penile CA prompted use of EGFR targeted
monotherapy using anti-EGFR monoclonal antibodies,
Panitumumab and Cetuximab.
• A number of studies have demonstrated a high expression of
Programmed death ligand1(PD-L1) in metastatic penile cancers
• A phase Il trial in metastatic penile cancer patients comparing
cabozajnib/nivolumab/ipilimumab to cabozantinib/nivolumab
demonstrated a partial response in 50% of the patients (2/4) and a
stable disease in the other 50% (2/4).
• Several key trials are currently underway to evaluate role of immune
checkpoint inhibitors, mainly nivolumab and pembrolizumab, in
advanced penile cancer patients.
 NONSQUAMOUS PENILE MALIGNANT
NEOPLASMS
 BASAL CELL CARCINOMA
• Rare
• Highly curable variant with
low metastatic potential
• Treatment is by local excision

 MELANOMA
• Blue-black or reddish brown pigmented
papule, plaque,
• ulceration on glans penis.
• Prepuce less frequently.
• Surgery-primary mode of treatment;
• Radiation therapy & chemotherapy
are of only adjunctive or palliative benefit.
 SARCOMA
• Malignant lesions –on proximal shaft
• Benign lesions-often located distally.
• M/C malignant lesions: vascular origin
(hemangioepithelioma) followed by neural,
myogenic, and fibrous origin
• Surgery treatment of choice
• Local recurrences are characteristic of
sarcomas
 EXTRAMAMMARY PAGET DISEASE

• Erythematous, eczematous, well-demarcated

area
• HPE: Large, round or oval, clear-staining
hydropic cells with hypochromatic nuclei
(Paget cells).
• In most cases only the skin and dermis
must be resected with a gross margin
of up to 3 cm.
 METASTASES

• Bladder ,Prostate, and Rectum

• Most frequent sign of penile metastasis is priapism; penile swelling,
nodularity, and ulceration
• Prognosis is poor
• Therapy directed toward primary tumor's histology or local palliation
is advised
RECENT ADVANCES
• WHO classification of tumors of the penis

Non-HPV-related HPV-related
SCC, usual type Basaloid SCC
Pseudohyperplastic carcinoma Papillary basaloid carcinoma
Verrucous carcinoma Warty carcinoma
Carcinoma cuniculatum Warty-basaloid carcinoma
Papillary carcinoma NOS Clear-cell carcinoma
Adenosquamous carcinoma Lymphoepithelioma-like carcinoma
Sarcomatoid carcinoma
Mixed squamous cell carcinoma
 Primary
Trial/drug Phase Setting Intervention
endpoint

Locally
advanced or
metastatic,
Avelumab Objective
Alpaca Phase II after
alone response rate
progression or
unfit for
chemotherapy

Advanced Maintenance
disease. avelumab Progression-
Pulse Phase II
Maintenance after free survival
therapy chemotherapy
 Primary
Trial/drug Phase Setting Intervention
endpoint
Arm A:
Arm A: Locally atezolizumab 
advanced + radiotherapy Progression-
Pericles Phase II (inoperable) free survival
Arm B: at 1 year
Metastatic Arm B:
atezolizumab

Pembrolizumb
Advanced Overall
 + standard-of-
Hercules Phase II disease first- response rate
care
line therapy at week 24
chemotherapy
 REFERENCES
• CAMPBELL WALSH UROLOGY; Pg1742-1775
• Bailey and Love Pg
• LANGMAN’S Medical Embryology
• GRAY’s Anatomy
• Google Scholar
• Roshanlal recent advances Pg 192-216
THANK YOU