Penile Cancer

Benign Penile Lesions

• Papilloma (pearly penile papules) → no treatment
• Condyloma acuminatum → HPV (6 & 11); stays superficial, never invades
• Zoon's balanitis (plasma cell balanitis) → uncircumcised men, 3rd decade+; mimics CIS → → circumcision (curative)

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Premalignant Lesions

Lesion	Key	Progression to invasive
Giant condyloma (Buschke–Löwenstein / verrucous)	HPV 6 & 11; locally invades & destroys by compression, but does NOT metastasize	30%
Bowenoid papulosis	Reddish-brown papules, shaft of young men; HPV 16	1%
CIS — Bowen disease	Penile shaft	5%
CIS — Erythroplasia of Queyrat	Glans / foreskin	30%
BXO (balanitis xerotica obliterans = lichen sclerosus)	—	—

• Non-HPV also includes: penile Kaposi sarcoma (HHV-8 → screen HIV; start HAART first), leucoplakia, pseudoepitheliomatous keratotic balanitis

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Squamous Cell Carcinoma (SCC) of the Penis

• >95% of penile malignancies; abrupt incidence rise in 6th decade

Risk factors

1. Uncircumcised
2. Premalignant lesions
3. HPV 16 & 18
4. Chronic inflammation (lichen sclerosus, phimosis)
5. Tobacco, poor hygiene/low SES, multiple partners, PUVA

Circumcision: before puberty lowers invasive cancer risk; does NOT lower risk of CIS. Adult circumcision offers little/no protection.

Presentation

• Painless penile lesion (pain uncommon; care-seeking delay common)
• Site frequency: Glans (48%) > prepuce (21%) > shaft
• ~50% present with a palpable inguinal node (of palpable nodes, only ~43% are truly metastatic — rest inflammatory)

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Staging (TNM, AJCC 8th)

T stage

Stage	Description
Tis	Carcinoma in situ
Ta	Non-invasive
T1a	Subepithelial; no LVI/PNI and not high grade
T1b	Subepithelial; with LVI, PNI, or high grade (G3-4/sarcomatoid)
T2	Invades corpus spongiosum
T3	Invades corpus cavernosum
T4	Invades adjacent structures

N stage

Stage	Clinical (cN)	Pathological (pN)
N1	One unilateral mobile node	≤2 unilateral positive nodes
N2	≥2 unilateral mobile, or bilateral	≥3 unilateral, or bilateral
N3	Fixed nodal mass	Extranodal extension or pelvic node

• Note: clinically, N3 = fixed mass; pelvic nodes are captured as pN3 pathologically — AJCC separates these. Node >4 cm often = extranodal extension.

M stage

• M1 — distant metastasis (node mets outside true pelvis, or visceral/bone). Most common sites: lung, bone, liver (late). Untreated → death in majority within 2 years.

Pathology variants

• Classic
• Verrucous → excellent prognosis (does not metastasize; observe)
• HPV-related
• Sarcomatoid → very aggressive

Strongest prognostic factor for survival → extent of lymph node metastasis.

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Lymphatic Spread & Inguinal Anatomy

Pattern of spread

Most common metastasis = inguinal lymph nodes (ILN):

Penis → sentinel node → superficial nodes → deep nodes → pelvic nodes → distant mets

Inguinal anatomy (lateral → medial): "NAVEL"

Letter	Structure
N	Nerve
A	Artery
V	Vein
E	Empty space
L	Lymphatics (→ lymph nodes)

• Fascia lata divides superficial from deep lymph nodes
• Node of Cloquet = most cephalad deep node; marks the inguinal/pelvic boundary

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Workup

• History & physical (incl. inguinal node exam — number, fixed vs mobile per side)
• Biopsy → assess depth, vascular invasion, grade (Broder 1–4; G1-2 = 70-80% at dx)
• Imaging → small glanular lesion = none; larger/invasion = US (Doppler US > MRI for corporal invasion); CT/PET for pelvic nodes; CT C/A/P + bone scan for distant
• Non-palpable inguinal node → DSNB (dynamic sentinel node biopsy) if ≥pT1b
• Palpable inguinal node → FNAC/biopsy (see node algorithm)

DSNB = Tc-99m nanocolloid lymphoscintigraphy + patent blue dye + intraop gamma probe; target false-negative rate ≤5%; preferred for cN0 staging. ~20% of cN0 groins harbor occult mets.

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Management of the Primary Tumour

Before choosing, identify:

• T stage: Tis/Ta · T1a/T1b · T2/T3 · T4
• Node status: non-palpable · palpable mobile <4 cm · fixed or >4 cm or N3 (= pelvis)
• Penile-sparing desired? Yes / No
• Lesion location: glans · distal · proximal

Scenario	Treatment
Tis, Ta · N0–N2 <4 cm	Topical 5-FU, laser, wide local excision, Mohs
T1a, T1b · N0–N2 <4 cm · penile-sparing	Radiation or wide local excision
T2, T3 · N0–N2 <4 cm · penile-sparing	Radiation
T1–T3 · N0–N2 <4 cm · no sparing · glans	Glansectomy (if no urethral/cavernosal involvement); partial penectomy if urethra/cavernosum involved
T1–T3 · N0–N2 <4 cm · no sparing · distal	Partial penectomy
T1–T3 · N0–N2 <4 cm · no sparing · proximal	Total penectomy
T4, N3 or >4 cm, or M1	Chemotherapy

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Inguinal Lymph Node Management Algorithm

Step 1 — Identify: primary risk (Tis/Ta · T1a = low | T1b–T4 = high) · node exam (none · mobile <4 cm · fixed/>4 cm) · laterality

POSITIVE pathway = ipsilateral dissection: superficial inguinal + deep + pelvic

Step 2 — Choose row by primary risk + node exam

Primary	Node on exam	Management
Tis / Ta	Palpable	Antibiotics ×4 wk → if persists, FNAC → see Step 3
T1a	Palpable	FNAC → see Step 3
T1b–T4	None (cN0)	Bilateral superficial ILND + frozen → if +ve, complete deep
T1b–T4	Unilateral mobile <4 cm	POSITIVE pathway (ipsilateral) + contralateral superficial (frozen)
T1b–T4	Bilateral mobile	FNAC → −ve: bilateral superficial ILND + frozen · +ve: neoadjuvant chemo OR bilateral dissection
Any	Fixed (cN3) / >4 cm	Neoadjuvant chemo → radical ILND in responders

Step 3 — FNAC outcome (low-risk primary: Tis/Ta, T1a)

FNAC result	Next step	Then
Positive	→ POSITIVE pathway	—
Negative	→ Excisional biopsy	+ve → POSITIVE pathway · −ve → OBSERVE

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Adjuvant Chemotherapy — Indications

1. ≥2 positive nodes
2. Bilateral metastases
3. Pelvic nodes
4. Extranodal extension