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Penile Cancer

EAU-ASCO Collaborative Guidelines on Penile Cancer. Last updated: Mar 2023.

NICE guideline [NG12] Suspected cancer: recognition and referral. 1.6 Urological cancers. Last updated: May 2025.

Histology

95% of penile cancers are squamous cell carcinomas

Aetiology

Penile cancers usually arise from the epithelium of the glans or inner prepuce (foreskin)

 

Risk factors:

  • HPV infection (esp. HPV 16, and also HPV 18) – main risk factor (1/3 cases are attributed to HPV-associated carcinogenesis)
  • Lichen sclerosus
  • Phimosis (due to associated chronic infections)
  • Smoking, low socioeconomic status, and low level of education

Neonatal circumcision reduces the incidence of penile cancer. Circumcision removes the risk of phimosis (and associated chronic infection), and the site of potential carcinogenesis (as penile cancer can arise from the prepuce).

Clinical Features

Note that the appearance of penile tumours can be heterogeneous:

  • Visible or palpable lesions on the penis, often raised or ulcerous
  • Possible local destruction of penile tissue
  • Lesions may be hidden under the foreskin, especially if phimosis is present

Penile cancer first metastasises to the inguinal lymph nodes (check for inguinal lymphadenopathy).

High-yield anatomy + oncology fact:

  • The penis (and scrotum) primarily drains lymph to the inguinal lymph nodes
  • The testis primarily drains lymph to the para-aortic lymph nodes

Red Flags and Referral Criteria

Consider a suspected penile cancer pathway referral if ANY of the following:

  • Penile mass / ulcerative lesions + STI has been excluded
  • Persistent penile lesion after treatment for a STI
  • Unexplained / persistent symptoms affecting the foreskin / glans

Investigation and Diagnosis

Confirmatory test: penile biopsy for histology

 

Other investigations:

  • MRI indicated if there is uncertainty regarding corporal invasion or the feasibility of organ-sparing surgery
  • Assess for inguinal lymphadenopathy 
    • Ultrasound and fine needle aspiration for suspicious nodes
    • Surgical lymph node staging (direct sentinel node biopsy / node dissection) in high-risk patients without palpable nodes
    • Confirm nodal metastasis by biopsy
  • Staging: CT or PET/CT (indicated primarily in those with nodal metastases)

Management

General approach:

Disease Management
Superficial non-invasive disease / invasive disease confined to the glans Penile-preserving surgery (e.g. laser ablation, local excision, radiation therapy)
Locally advanced disease (T3-T4) with involvement of the corpora cavernosa / urethra Partial / total penectomy
  • Distal / midshaft disease → partial penectomy
  • Extensive tumour involving the base / entire penile shaft → total penectomy
+ve Lymph node disease Radical inguinal lymph node dissection

The presence and extent of nodal metastases are the most important prognostic factors for survival

References

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