Excerpt from Penile Cancer

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Penile carcinoma

Penile malignancies are uncommon, but, when they are diagnosed, they are psychologically devastating to the patient and often present a challenge to the urologist. Benign, premalignant, and malignant conditions must be distinguished from each other. Malignancies are usually squamous cell carcinomas and behave similarly to those occurring elsewhere on the skin.

Patients with carcinoma of the penis tend to delay seeking medical attention. Of these patients, 15-50% delay seeking medical attention for more than 1 year. This delay is attributed to embarrassment, guilt, fear, ignorance, and personal neglect. Patients often try to treat themselves with various skin creams and lotions. These may appear to be effective for a time, which further delays the diagnosis.

Delays may also occur because of the physician. Patients report that they receive various salves and antibiotics from their primary care physicians before they see a urologist. Whether or not delays in diagnosis and therapy affect survival is uncertain, but the ability to eliminate the cancer and retain a functioning and cosmetically satisfactory result is affected.

History of the Procedure

The typical therapy for penile cancer has been surgical. Superficial carcinomas have been managed with local resection, while invasive disease has been managed with partial or total penectomy and some degree of lymphadenectomy.

If men are diagnosed with invasive disease but no evidence of nodal metastases, some can be treated with local resection and penile reconstruction. Radiation therapy is applicable for some of these men.

The presence of a sentinal node has been identified in many of these men. Various imaging techniques have shown increasing sensitivity for finding these nodes and sparing some patients the need for bilateral inguinal lymphadenectomy.

Problem

Penile tumors can originate anywhere on the penis but are most commonly found on the glans (48%) and prepuce (21%). Tumors involve the glans and prepuce in 9%, the coronal sulcus in 6%, and the shaft in less than 2%. The common sites of origin may be related to constant exposure to smegma and other irritants within the prepuce.

Patients who are diagnosed with penile cancer have a variety of treatment options if the tumor is smaller than 2 cm and particularly if it is confined to the prepuce. The cancers tend to remain confined to the skin for long periods, but, when they invade into the deeper tissues, they have a greater propensity to invade lymphatics and blood vessels.

Frequency

Penile cancer is rare in Western countries; approximately 1000 men each year are diagnosed with this disease. This cancer accounts for 0.4-0.6% of all malignancies in the United States and Europe. In the rest of the world, the situation is different and represents an important health problem. Penile carcinoma represents 20-30% of all cancers diagnosed in men living in Asia, Africa, or South America.

In urban India, the age-adjusted incidence varies from 0.7-2.3 cases per 100,000 men. In rural India, the rate is 3 cases per 100,000 men. This accounts for more than 6% of all malignancies in men.

In Brazil the age-adjusted incidence is 8.3 cases per 100,000 people. In Uganda, this is the most commonly diagnosed cancer, with 1% of men being diagnosed by age 75 years.

The disease rarely occurs in circumcised men, particularly if they were circumcised as a neonate.

Penile cancer tends to be a disease of older men, with an abrupt increase in incidence in men aged approximately 60 years; incidence peaks in men aged 80 years. However, the tumor is not unusual in younger men. One study reported that 22% of the patients were younger than 40 years and 7% were younger than 30 years.

Etiology

The frequency of penile carcinoma varies according to hygienic practices and cultural and religious beliefs. Phimosis is present in at least 25-75% of men with this disease. Information about the presence of phimosis is often not recorded in underdeveloped countries.

Circumcision has been well established as an effective prophylactic measure for this type of cancer. Data from most large series have demonstrated that the disease is almost never observed in individuals who are circumcised in the neonatal period. The disease is found more frequently when circumcision is delayed until puberty. Adult circumcision offers little or no protection.

No firm evidence indicates that smegma acts as a carcinogen, although this belief is widely held. The role of viral infection continues to be studied. Both penile cancer in men and cervical cancer in women have been associated with the presence of herpes virus infection and human papilloma virus infection. In women whose sexual partners had penile cancer, the prevalence of cervical cancer is increased 3- to 8-fold. Human papilloma viruses 16 and 18 have been found in one third of men with penile cancer. Whether these viruses are involved with causation of the cancer or are found as saprophytes has not been determined.

Abnormalities considered to be premalignant include cutaneous horns, pseudoepitheliomatous keratotic and micaceous balanitis, balanitis xerotica obliterans, giant condyloma, and bowenoid papulosis (bowenoid papulosis is a benign condition). Penile intraepithelial neoplasia is also considered a precursor, but only 5-15% of these lesions develop into invasive squamous cell carcinoma. When carcinoma in situ (CIS) occurs on the glans, it is termed erythroplasia of Queyrat; however, when it occurs on the follicle-bearing skin of the shaft, it is termed Bowen disease.

The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program was used to gather data on 1605 men diagnosed with squamous cell carcinoma of the penis. CIS was diagnosed in 37% of this population, localized disease was diagnosed in 39%, regional disease was present in 13%, distant disease was present in 2.3%, and unstaged disease remained in 7.9%.

The proportion of men presenting annually with CIS tended to increase, although the number of men with localized disease decreased. Older age at the time of diagnosis was associated with a higher stage of disease.

The mean time until death from cancer was 66.6 months for those with CIS, 50.1 months for those with localized disease, 32.4 months for those with regional disease, and 7.4 months for those with distant metastases. Overall, 22.4% of the patients in this database died of this cancer.

Pathophysiology

Penile cancers begin as small lesions on the glans or prepuce. They gradually grow laterally along the surface, covering the entire glans and prepuce and invading the corpora and shaft of the penis. The cancers may be papillary and exophytic or flat and ulcerative. Untreated, penile autoamputation can occur.

The growth rates of the papillary and ulcerative lesions are similar, but the flat ulcerative lesions have a tendency to metastasize to the lymph nodes earlier and, therefore, are associated with a lower 5-year survival rate. Cancers larger than 5 cm and those involving more than 75% of the shaft are associated with a high prevalence of nodal metastases and a lower survival rate, but a consistent relationship among the size of the cancer, the presence of inguinal node metastases, and survival has not been identified.

The Buck fascia, which surrounds the corpora, acts as a temporary barrier. Eventually, the cancer penetrates the Buck fascia and the tunica albuginea, where the cancer has access to the vasculature and from which systemic spread is possible.

Metastasis to the femoral and inguinal lymph nodes is the earliest path for tumor dissemination. The lymphatics of the prepuce join with those from the shaft. These drain into the superficial inguinal nodes.

The lymphatics of the glans follow a different path and join those draining the corpora. A circular band of lymphatics that drains to the superficial nodes is located at the base of the penis.

The superficial inguinal nodes drain to the deep inguinal nodes, which are beneath the fascia lata. From here, drainage is to the pelvic nodes. Multiple cross connections exist at all levels, permitting bilateral penile lymphatic drainage.

Untreated, metastatic enlargement of the regional nodes leads to skin necrosis, chronic infection, and, eventually, death from sepsis or hemorrhage secondary to erosion into the femoral vessels. Clinically apparent distant metastases to the lung, liver, bone, or brain are unusual until late in the course of the disease, often after the primary disease has been treated. Distant metastases are usually associated with regional node involvement.

Penile carcinoma follows a relentless and progressive course that is fatal for most untreated patients within 2 years. Spontaneous remission has not been reported.

Clinical

Patients present with a lesion that has failed to heal, a subtle induration in the skin, a small excrescence, a papule, a pustule, a warty growth, or a large exophytic growth. A cancer may be a shallow erosion or a deep ulceration with rolled edges. Because most of these patients are uncircumcised, they may have a phimosis that obscures the tumor and allows it to grow undetected. Many men do not seek medical attention until the cancer has eroded through the prepuce and become malodorous because of infection and necrosis. Occasionally, this cancer is found incidentally on histopathology during a circumcision.

Rarely, a mass, an ulceration, a suppuration, or hemorrhage may manifest in the inguinal area because of nodal metastases.

Few symptoms are associated with the development of these cancers. Even when significant local destruction of tissue occurs, pain is infrequent. Patients with advanced metastatic cancer may report weakness, weight loss, and fatigue; the penile lesion may bleed.

The presence of a nonhealing penile lesion usually prompts the patient to visit a physician. While a carcinoma may manifest as a hyperemic patch on the glans characteristic of erythroplasia of Queyrat or as an ulcerated growth on the inner surface of the prepuce, the differential diagnosis includes benign and premalignant lesions.

Penile lesions can be categorized as benign, premalignant, and malignant neoplasms.

Benign lesions include pearly penile papules, hirsute papillomas, and coronal papillae. These lesions do not require treatment and are usually found on the glans in uncircumcised males. Rashes, ulcerations from irritation, and allergic reactions or infections must be considered.

Some histologically benign lesions are potentially malignant (premalignant) or have been associated with the presence of squamous cell carcinoma. The most common is balanitis xerotica obliterans. This is a variation of lichen sclerosis et atrophicus and manifests as a white patch on the prepuce or glans, where it usually involves the urethral meatus.

Leukoplakia manifests as solitary plaque or multiple whitish plaques, which often involve the meatus. Leukoplakia has been associated with squamous cell carcinoma.

Viral lesions include condyloma acuminata, which are soft papillomatous growths. They are known as venereal warts and have a predilection for the genital and perineal regions. These lesions are usually sexually transmitted by the human papilloma virus (see Human Papillomavirus for more information). Viral types 6, 11, 42, and 44 are associated with low-grade dysplasia. Types 16, 18, 31, 33, 35, and 39 are associated with neoplastic changes.

Kaposi sarcoma manifests as a cutaneous neovascular lesion that is raised, usually painful, and often ulcerated with a bluish discoloration. Patients with AIDS are predisposed to develop this condition.

Giant condyloma acuminata or a Buschke-Löwenstein tumor differs from the standard condyloma in that it displaces, invades, and destroys adjacent structures by compression, whereas the standard condyloma remains superficial and never invades. Despite their large size and invasive potential, Buschke-Löwenstein tumors show no signs of malignant change upon histologic examination.

Malignant carcinomas include variants of squamous cell carcinoma such as CIS, erythroplasia of Queyrat, or Bowen disease. The diagnosis depends on their appearance and the site of origin. Erythroplasia involves the glans, prepuce, or penile shaft, while similar lesions on the remainder of the genitalia and perineum are termed Bowen disease. Regardless of the terminology and clinical presentation, these are carcinomas with the same malignant potential; biopsies should be performed, and the carcinoma should be staged and treated.

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