Abstract

Penile cancer is a malignant growth found on the skin or in the tissues of the penis. Around 95% of penile cancers are squamous cell carcinomas. Other types of penile cancer such as Merkel cell carcinoma, small cell carcinoma, melanoma and other are generally rare.

Classification

Around 95% of penile cancers are squamous cell carcinomas. They are classified into the following types:

- basaloid (4%)

- warty (6%)

- mixed warty-basaloid (17%)

- verrucous (8%)

- papillary (7%)

- other SCC mixed (7%)

- sarcomatoid carcinomas (1%)

- not otherwise specified (49%)

Other types of carcinomas are rare and may include small cell, Merkel cell, clear cell, sebaceous cell or basal cell tumors. Non-epithelial malignancies such as melanomas and sarcomas are even more rare.

Classification | Staging

Like many malignancies, penile cancer can spread to other parts of the body. It is usually a primary malignancy, the initial place from which a cancer spreads in the body. Much less often it is a secondary malignancy, one in which the cancer has spread to the penis from elsewhere. The staging of penile cancer is determined by the extent of tumor invasion, nodal metastasis, and distant metastasis.

The T portion of the AJCC TNM staging guidelines are for the primary tumor as follows:

- TX: Primary tumor cannot be assessed.

- T0: No evidence of primary tumor.

- Tis: Carcinoma "in situ".

- Ta: Noninvasive verrucous carcinoma.

- T1a: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3–4).

- T1b: Tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated.

- T2: Tumor invades the corpus spongiosum or cavernosum.

- T3: Tumor invades the urethra or prostate.

- T4: Tumor invades other adjacent structures.

Anatomic Stage or Prognostic Groups of penile cancer are as follows:

- Stage 0—Carcinoma "in situ".

- Stage I—The cancer is moderately or well differentiated and only affects the subepithelial connective tissue.

- Stage II—The cancer is poorly differentiated, affects lymphatics, or invades the corpora or urethra.

- Stage IIIa—There is deep invasion into the penis and metastasis in one lymph node.

- Stage IIIb—There is deep invasion into the penis and metastasis into multiple inguinal lymph nodes.

- Stage IV—The cancer has invaded into structures adjacent to the penis, metastasized to pelvic nodes, or distant metastasis is present.

Classification | HPV positive tumors

Human papillomavirus prevalence in penile cancers is high at about 40%. HPV16 is the predominant genotype accounting for approximately 63% of HPV-positive tumors. Among warty/basaloid cancers the HPV prevalence is 70–100% while in other types it is around 30%.

Pathogenesis

Penile cancer arises from precursor lesions, which generally progress from low-grade to high-grade lesions. For HPV related penile cancers this sequence is as follows:

- A. Squamous hyperplasia;

- B. Low-grade penile intraepithelial neoplasia (PIN);

- C. High-grade PIN (carcinoma in situ—Bowen's disease, Erythroplasia of Queyrat and bowenoid papulosis (BP));

- D. Invasive Carcinoma of the Penis.

However, in some cases non-dysplastic or mildly dysplastic lesions may progress directly into cancer. Examples include flat penile lesions (FPL) and condylomata acuminata.

In HPV negative cancers the most common precursor lesion is lichen sclerosus (LS).

Treatment

There are several treatment options for penile cancer, depending on staging. They include surgery, radiation therapy, chemotherapy, and biological therapy. The most common treatment is one of five types of surgery:

- Wide local excision—the tumor and some surrounding healthy tissue are removed

- Microsurgery—surgery performed with a microscope is used to remove the tumor and as little healthy tissue as possible

- Laser surgery—laser light is used to burn or cut away cancerous cells

- Circumcision—cancerous foreskin is removed

- Amputation (penectomy)—a partial or total removal of the penis, and possibly the associated lymph nodes.

Radiation therapy is usually used adjuvantly with surgery to reduce the risk of recurrence. With earlier stages of penile cancer, a combination of topical chemotherapy and less invasive surgery may be used. More advanced stages of penile cancer usually require a combination of surgery, radiation and chemotherapy.

In addition to all the above, treatment of the underlying disease like brucellosis, is important to limit disease recurrence.

Prognosis

Prognosis can range considerably for patients, depending where on the scale they have been staged. Generally speaking, the earlier the cancer is diagnosed, the better the prognosis. The overall 5-year survival rate for all stages of penile cancer is about 50%.

Epidemiology

Penile cancer is a rare cancer in developed nations with annual incidence varying from 0.3 to 1 per 100,000 per year accounting for around 0.4–0.6% of all malignancies. The annual incidence is approximately 1 in 100,000 men in the United States, 1 in 250,000 in Australia, and 0.82 per 100,000 in Denmark. In the United Kingdom, fewer than 500 men are diagnosed with penile cancer every year.

However, in the developing world penile cancer is much more common. For instance, in Paraguay, Uruguay, Uganda and Brazil the incidence is 4.2, 4.4, 2.8 and 1.5–3.7 per 100,000, respectively. In some South American countries, Africa, and Asia, this cancer type constitutes up to 10% of malignant diseases in men.

The lifetime risk has been estimated as 1 in 1,437 in the United States and 1 in 1,694 in Denmark.