Penile cancer refers to malignant tumors originating from the epithelial cells of the glans penis, coronal sulcus, or inner foreskin. The overall incidence is low, accounting for less than 1% of newly diagnosed male malignancies. There are significant regional variations due to differences in race, religious beliefs, socioeconomic development, and sanitary conditions.
Etiology and Pathology
Recognized risk factors for penile cancer include human papillomavirus (HPV) infection, phimosis or redundant foreskin, smegma accumulation, smoking, chronic balanoposthitis, and radiation exposure.
The majority of penile cancers are squamous cell carcinomas (SCC), which can be further classified based on HPV association. Non-HPV-related types include keratinizing SCC, verrucous carcinoma, papillary carcinoma, adenosquamous carcinoma, sarcomatoid carcinoma, and mixed carcinoma. HPV-related subtypes include basaloid carcinoma, warty carcinoma, and lymphoepithelioma-like carcinoma.
Based on growth patterns, penile cancer can be divided into papillary and nodular types. Papillary carcinomas are predominantly exophytic, may break through the foreskin, and present with uneven tumor surfaces often accompanied by ulcers, foul-smelling purulent discharge, and progression to a typical cauliflower-like appearance. Nodular carcinomas exhibit infiltrative growth and are relatively hard. They may cause ulcers and invade deeply into the penile erectile tissue. However, due to the dense tunica albuginea surrounding the corpus spongiosum, penile cancer rarely invades the urethra to cause urinary obstruction unless in advanced stages.
Penile cancer primarily spreads via lymphatic metastasis to the inguinal and iliac lymph nodes. Hematogenous dissemination may occur, leading to metastasis in the lungs, liver, bones, and brain.
Clinical Presentation
Penile cancer is often seen in men aged 40–60 years with phimosis or redundant foreskin. The tumor typically grows under the foreskin, starting as a small lesion that progressively invades the glans penis, the shaft, and the erectile tissues, making early detection challenging.
If the foreskin can be retracted to expose the glans penis, early lesions may present as papules, warty erythematous plaques, or non-healing ulcers. In cases of phimosis where the glans remains hidden, patients may report itching or burning sensations under the foreskin and may detect a hard mass within. There may also be bloody or purulent secretions from beneath the foreskin. With disease progression, the tumor may protrude through or penetrate the foreskin, adopting a cauliflower-like appearance with necrotic ulcers and a foul-smelling exudate. Advanced tumors may invade the entire penis and corpus spongiosum, leading to urinary difficulties, retention, or fistula formation. Physical examination often reveals enlarged, hard inguinal lymph nodes.
Diagnosis and Differential Diagnosis
Diagnosis of penile cancer is generally straightforward but is often delayed due to patient neglect or embarrassment. For men over 40 with phimosis or redundant foreskin presenting with the aforementioned symptoms, tissue biopsy should confirm the diagnosis. Enlarged, hard, immobile inguinal lymph nodes with no tenderness raise suspicion for lymph node metastasis, which can be evaluated with ultrasound-guided fine needle aspiration biopsy. Imaging studies such as ultrasound, CT, and MRI are helpful in assessing metastasis to inguinal lymph nodes, pelvic lymph nodes, and distant organs.
Penile cancer must be differentiated from conditions like condyloma acuminatum (genital warts), syphilitic chancre, and chronic balanoposthitis.
Treatment
Surgical Treatment
Depending on the stage of the disease, treatment options include local lesion excision, partial penectomy, or total penectomy. Regional lymph node metastasis significantly affects patient survival. Patients with poorly differentiated tumors or regional lymph node metastasis should undergo inguinal lymph node dissection. For cases with three or more inguinal lymph node metastases, extracapsular nodal invasion, or suspected pelvic lymph node metastasis based on imaging, pelvic lymphadenectomy is indicated.
Radiotherapy
Radiotherapy can serve as salvage or palliative treatment for patients who are inoperable, have postoperative recurrence, or exhibit regional lymph node metastasis.
Chemotherapy
Patients with unresectable tumors or extensive metastasis involving multiple inguinal or pelvic lymph nodes should undergo chemotherapy. Commonly used regimens include the TIP protocol (paclitaxel + ifosfamide + cisplatin), BMP protocol (bleomycin + methotrexate + cisplatin), or TPF protocol (paclitaxel + cisplatin + 5-fluorouracil).