- Squamous cell carcinoma accounts for >95% of penile malignancies; incidence rises abruptly in the 6th decade.
- Neonatal circumcision almost eliminates the risk of invasive penile cancer; adult circumcision offers little to no protection and circumcision does not provide the same level of protection against CIS.
- HPV is a major risk factor: subtype 16 most frequently involved; oncogenic subtypes are 16 and 18, non-oncogenic subtypes are 6 and 11.
- HPV status is mandatory to determine when a patient is diagnosed with penile cancer.
- Progression rate to invasive cancer by premalignant lesion: bowenoid papulosis 1%, verrucous carcinoma (Buschke-Löwenstein) 30%, erythroplasia of Queyrat 30%, Bowen's disease 5%.
- Verrucous carcinoma exhibits progressive local growth but does not metastasize; palpable adenopathy in verrucous carcinoma is very likely reactive and should be initially observed.
- AJCC 8th edition: T1a is without LVI, perineural invasion, and not high-grade; T1b is with any of those features; T2 invades corpus spongiosum; T3 invades corpus cavernosum; T4 invades adjacent structures.
- Pathological N staging: pN1 = up to 2 unilateral positive inguinal nodes; pN2 = ≥3 unilateral or bilateral inguinal nodes; pN3 = extra-nodal extension or pelvic lymph node(s); a lymph node >4 cm is often associated with extranodal extension.
- Risk factors for nodal metastases: high-grade disease, depth of invasion (pT stage), sarcomatoid tumors, perineural invasion, and vascular invasion.
- Most common sites of distant metastases are lung, bone, and liver; priapism is the most frequently encountered sign of metastatic involvement of the penis.
- Lymph node involvement is the most important prognostic factor for survival; 5-year survival is higher without nodal involvement (~73%) than with it (~60%), and the node-positive figure ranges widely (0–86%) by extent of involvement.
- ≈20% of patients with clinically nonpalpable inguinal nodes harbor occult metastases; cross-sectional imaging cannot reliably detect them.
- Immediate resection of clinically occult lymph node metastases is associated with improved survival compared with delayed resection at clinical detection.
- Dynamic sentinel node biopsy (DSNB) is the preferred surgical staging option for cN0 high-risk patients and should be performed with a target false-negative rate of ≤5%.
- Indications for ipsilateral pelvic lymph node dissection during ILND: ≥2 positive inguinal nodes OR extracapsular nodal metastasis (pN3); PLND includes the distal common iliac, external iliac, and obturator nodes.
- Long-term survival is <10% if cancer has spread to the pelvic nodes; no anatomic or lymphangiographic studies demonstrate direct lymphatic drainage from the penis to the pelvic nodes (no skip lesions reported).
- Fixed inguinal lymph nodes (cN3) are managed with neoadjuvant chemotherapy followed by radical inguinal lymphadenectomy in responders.
- Adjuvant chemotherapy is indicated in pN2/pN3 patients after radical lymphadenectomy; cisplatin-containing regimens are used for advanced metastatic disease.
- Penile lymphatics: the superficial system drains the prepuce and penile shaft skin to the superficial inguinal nodes; the deep system drains the glans penis to both the superficial inguinal nodes and the deep inguinal nodes of the femoral triangle.
- Standard radical ILND boundaries: superior = inguinal ligament; medial = adductor longus aponeurosis; lateral = sartorius muscle; inferior = apex of femoral triangle/fossa ovalis; floor = pectineus for deep dissection (fascia lata for superficial).
- Modified ILND limits dissection by excluding the areas lateral to the femoral artery and caudal to the fossa ovalis, preserves the saphenous vein, eliminates the need for sartorius transposition, and uses thicker skin flaps.
- The node of Cloquet is the most proximal node in the femoral canal and is considered the margin between the inguinal and pelvic lymph nodes.
- Skin flaps should leave a 6–8 mm thickness of subcutaneous tissue in contact with the skin to avoid necrosis; Camper's fascia can be preserved to protect the superficial blood supply.
- Modified dissection should be converted to a radical inguinal lymphadenectomy if positive inguinal lymph nodes are found on frozen section.
- Perioperative low-dose heparin may increase lymphatic leakage in ILND; compression boots alone are recommended for DVT prophylaxis.
- Complication rates of ILND are reported to be as high as 50%; complications include wound infection, skin flap necrosis, wound dehiscence, seroma/lymphocele, lymphedema, DVT, and sepsis.
- For melanoma, sarcoma, basal cell, and extramammary Paget disease of the penis, surgery is the primary mode of treatment; extramammary Paget disease may be associated with other GU malignancies (prostate, bladder, renal) which should be evaluated.