Epidemiology & Risk Factors
Carcinoma of the penis accounts for less than 1% of cancers among males in the United States, with approximately 1-2 new cases being reported per 100,000 men. There is marked variation in incidence with geographic location. In areas such as Africa and regions of South America, penile carcinoma may compose 10-20% of all malignant lesions. Penile carcinoma occurs most commonly in the sixth decade of life, although rare case reports have included children.
The one etiologic factor most commonly associated with penile carcinoma is poor hygiene. The disease is virtually unheard of in males circumcised near birth. One theory postulates that smegma accumulation under the phimotic foreskin results in chronic inflammation leading to carcinoma. A viral cause has also been suggested as a result of the association of this tumor with cervical carcinoma.
A. Precancerous Dermatologic Lesions
Leukoplakia is a rare condition that most commonly occurs in diabetic patients. A white plaque typically involving the meatus is seen. Histologic examination reveals acanthosis, hyperkeratosis, and parakeratosis. This lesion may precede or occur simultaneously with penile carcinoma.
Balanitis xerotica obliterans is a white patch originating on the prepuce or glans and usually involving the meatus. The condition is most commonly observed in middle-aged diabetic patients. Microscopic examination reveals atrophic epidermis and abnormalities in collagen deposition.
Giant condylomata acuminata are cauliflowerlike lesions arising from the prepuce or glans. The cause is believed to be viral (human papillomavirus). These lesions may be difficult to distinguish from well-differentiated squamous cell carcinoma.
B. Carcinoma in Situ (Bowen Disease, Erythroplasia of Queyrat)
Bowen disease is a squamous cell carcinoma in situ typically involving the penile shaft. The lesion appears as a red plaque with encrustations.
Erythroplasia of Queyrat is a velvety, red lesion with ulcerations that usually involve the glans. Microscopic examination shows typical, hyperplastic cells in a disordered array with vacuolated cytoplasm and mitotic figures.
C. Invasive Carcinoma of the Penis
Squamous cell carcinoma composes most penile cancers. It most commonly originates on the glans, with the next most common sites, in order, being the prepuce and shaft. The appearance may be papillary or ulcerative.
Verrucous carcinoma is a variant of squamous cell carcinoma composing 5-16% of penile carcinomas. This lesion is papillary in appearance and on histologic examination is noted to have a well-demarcated deep margin unlike the infiltrating margin of the typical squamous cell carcinoma.
Patterns of Spread
Invasive carcinoma of the penis begins as an ulcerative or papillary lesion, which may gradually grow to involve the entire glans or shaft of the penis. Buck's fascia represents a barrier to corporal invasion and hematogenous spread. Primary dissemination is via lymphatic channels to the femoral and iliac nodes. The prepuce and shaft skin drain into the superficial inguinal nodes (superficial to fascia lata), while the glans and corporal bodies drain to both superficial and deep inguinal nodes (deep to fascia lata). There are many cross-communications, so that penile lymphatic drainage is bilateral to both inguinal areas. Drainage from the inguinal nodes is to the pelvic nodes. Involvement of the femoral nodes may result in skin necrosis and infection or femoral vessel erosion and hemorrhage. Distant metastases are clinically apparent in less than 10% of cases and may involve lung, liver, bone, or brain.
The staging system used most commonly in the United States was proposed by Jackson (1966), as follows: In stage I, the tumor is confined to the glans or prepuce. Stage II involves the penile shaft. Stage III has operable inguinal node metastasis. In stage IV, the tumor extends beyond the penile shaft, with inoperable inguinal or distant metastases.
The TNM classification of the American Joint Committee (1996) is given in Table 23-3.
The most common complaint at presentation is the lesion itself. It may appear as an area of induration or erythema, an ulceration, a small nodule, or an exophytic growth. Phimosis may obscure the lesion and result in a delay in seeking medical attention. In fact, 15-50% of patients delay for at least 1 year in seeking medical attention. Other symptoms include pain, discharge, irritative voiding symptoms, and bleeding.
Lesions are typically confined to the penis at presentation. The primary lesion should be characterized with respect to size, location, and potential corporal body involvement. Careful palpation of the inguinal area is mandatory because more than 50% of patients present with enlarged inguinal nodes. This enlargement may be secondary to inflammation or metastatic spread.
C. Laboratory Findings
Laboratory evaluation is typically normal. Anemia and leukocytosis may be present in patients with long-standing disease or extensive local infection. Hypercalcemia in the absence of osseous metastases may be seen in 20% of patients and appears to correlate with volume of disease.
Metastatic workup should include CXR, bone scan, and CT scan of the abdomen and pelvis. Disseminated disease is present in less than 10% of patients at presentation.
In addition to the dermatologic lesions discussed previously, carcinoma of the penis must be differentiated from several infectious lesions. Syphilitic chancre may present as a painless ulceration. Serologic and darkfield examination should establish the diagnosis. Chancroid typically appears as a painful ulceration of the penis. Selective cultures for Haemophilus ducreyi should identify the cause. Condylomata acuminata appear as exophytic, soft, "grape cluster" lesions anywhere on the penile shaft or glans. Biopsy can distinguish this lesion from carcinoma if any doubt exists.
A. Primary Lesion
Biopsy of the primary lesion is mandatory to establish the diagnosis of malignancy. Treatment varies depending on the pathology as well as the location of the lesion.
Carcinoma in situ may be treated conservatively in reliable patients. Fluorouracil cream application or neodymium:YAG laser treatment is effective for CIS and is preserving of the penis. Patients must come for frequent follow-up examinations to monitor response.
The goal of treatment in invasive penile carcinoma is complete excision with adequate margins. For lesions involving the prepuce, this may be accomplished by simple circumcision. For lesions involving the glans or distal shaft, partial penectomy with a 2-cm margin to decrease local recurrence has traditionally been suggested. For lesions involving the proximal shaft or when partial penectomy results in a penile stump of insufficient length for sexual function or directing the urinary stream, total penectomy with perineal urethrostomy has been recommended. Less aggressive surgical resections such as Mohs micrographic surgery and local excisions directed at penile preservation are currently being studied (Mohs et al, 1985).
B. Regional Lymph Nodes
As discussed previously, penile carcinoma spreads primarily to the inguinal lymph nodes. However, enlargement of inguinal nodes at presentation does not necessarily imply metastatic disease. In fact, up to 50% of the time this enlargement is caused by inflammation. Thus patients who present with enlarged inguinal nodes should undergo treatment of the primary lesion followed by a 4- to 6-week course of oral broad-spectrum antibiotics. Persistent adenopathy following antibiotic treatment should be considered to be metastatic disease, and sequential bilateral ilioinguinal node dissections should be performed. If lymphadenopathy resolves with antibiotics, observation in low-stage primary tumors (Tis, T1) is warranted. However, if lymphadenopathy resolves in higher-stage tumors, more limited lymph node samplings should be considered, such as the sentinel node biopsy described by Cabanas (1977) or a modified (limited) dissection as suggested by Catalona (1988) (Figure 23-3). If positive nodes are encountered, bilateral ilioinguinal node dissection should be performed. A decision tree for penile carcinoma is presented in Figure 23-4. Patients who initially have clinically negative nodes but in whom clinically palpable nodes later develop should undergo a unilateral ilioinguinal node dissection.
Patients who have inoperable disease and bulky inguinal metastases are treated with chemotherapy (cisplatin and 5-fluorouracil). In some cases regional radiotherapy can provide significant palliation by delaying ulceration and infectious complications and alleviating pain.
C. Systemic Disease
Four chemotherapeutic agents demonstrate activity against penile carcinoma: bleomycin, methotrexate, cisplatin, and 5-fluorouracil. However, no long-term responders have been reported. The rarity of the disease in the United States has resulted in limited clinical trials.
Survival in penile carcinoma correlates with the presence or absence of nodal disease. Five-year survival rates for patients with node-negative disease range from 65% to 90%. For patients with positive inguinal nodes, this rate decreases to 30-50% and with positive iliac nodes decreases to less than 20%. In the presence of soft-tissue or bony metastases, no 5-year survivors have been reported.
Other Penile Tumors
Squamous cell carcinoma accounts for 98% of penile cancers. Sporadic cases of melanoma, basal cell carcinoma, and Paget disease have been reported. The incidence of Kaposi sarcoma of the penis is increasing with the increasing prevalence of the human immunodeficiency virus. It appears as a painful papule on the glans or shaft with bluish-purple discoloration. These lesions tend to be radiosensitive.