ABSTRACT: Often overshadowed by more common genitourinary cancers, such as prostate, testicular, and kidney cancers, penile and urethral cancers nonetheless represent difficult treatment challenges for the clinician. The management of these cancers is slowly evolving. In the past, surgery, often extensive, was the treatment of choice. Recently, however, radiation and chemotherapy have begun to play larger roles as initial therapies, with surgery being reserved for salvage. With these modalities in their treatment armamentarium, oncologists may now be able to spare patients some of the physical and psychological sequelae that often follow surgical intervention without compromising local control and survival. Part 1 of this two-part article focuses on cancer of the penis. Part 2, which will appear in next month’s issue, discusses cancer of the urethra in both females and males. [ONCOLOGY 13(10):1347-1352, 1999]
Penile and urethral cancers, while less common than other genitourinary cancers, such as prostate, testicular, and kidney carcinomas, nonetheless represent difficult treatment challenges. The management of these cancers is slowly evolving as radiation therapy and chemotherapy begin to play larger roles in treatment. Part 1 of this two-part article focuses on cancer of the penis. Part 2, which will appear in next month’s issue, discusses cancer of the urethra in both females and males.
Cancer of the penis is a rare disease in western countries, where it is responsible for fewer than 1% of malignancies in male patients. Worldwide, however, penile cancer constitutes a major health problem, accounting for as many as 10% to 20% of cancers in males living in Asia, Africa, and South America. This cancer is virtually unknown in Jews who practice infant circumcision and is seen only rarely in Moslems who delay circumcision until the age of 3 to 13 years.
Cancer of the penis has been associated with phimosis and poor local hygiene. The human papilloma virus (HPV) may be an etiologic agent[2,3]; HPV-16, in particular, has been identified as a potential causative agent. Ultraviolet radiation also appears to have carcinogenic potential for squamous cell carcinoma of the penis.
The penis is composed of the corpus spongiosum and two corpora cavernosa enclosed within a fascial layer called Buck’s fascia (Figure 1). The corpus spongiosum expands distally into the glans penis, which is covered by the foreskin (prepuce).
Over 95% of cases of penile cancer are squamous cell carcinomas (Figure 2). Bowen’s disease, or carcinoma in situ, is also seen. Erythroplasia of Queyrat is a variant of carcinoma in situ. Approximately 18% of patients with acquired immune deficiency (AIDS)–related Kaposi’s sarcoma have lesions on the penis or genitalia. Other sarcomas, melanomas, basal cell carcinomas, and lymphomas have been reported but are extremely rare.[ 1] A 1992 review of the literature identified 277 cases of lesions metastatic to the penis.
The incidence of lymph node metastases from squamous cell carcinoma of the penis is related to histologic grade. Well-differentiated tumors have a far lower incidence of spread to the nodes than do moderately or poorly differentiated tumors. Verrucous carcinoma, a variant of squamous cell carcinoma, appears to have an especially low potential for metastatic nodal spread.
The skin of the penis and prepuce is drained primarily by the superficial inguinal nodes, while the glans is drained by the superficial inguinal nodes, and, along with the corpora, by the deep inguinal and iliac nodes.  The first site of metastasis from carcinoma of the penis is usually the inguinal nodes, with secondary involvement of the pelvic nodes.  Dessication of the superficial lymphatics at the base of the penis accounts for bilateral involvement.
Approximately 50% of patients with cancer of the penis present with palpable inguinal nodes. A course of antibiotic therapy is indicated in patients with palpable nodes, as only half will contain metastatic disease while the other half are inflamed secondary to infection of the primary tumor. Conversely, approximately 20% of patients with clinically N0 inguinal nodes will be found to have metastases in these nodes if prophylactic node dissection is undertaken.
The most common sites of distant metastatic disease are the lungs, liver, and bone. Clinical Presentation The clinical presentation of penile cancer varies from subtle areas of induration, erythema, or warty growth to obvious extensive carcinoma. The earliest symptoms include itching or burning under the foreskin and ulceration of the glans or prepuce, which can progress to a lump, mass, or nodule. With continued neglect, the lesion advances until a persistent, foul-smelling, purulent discharge exudes from beneath a frequently phimotic, nonretractable, distorted prepuce. Pain usually is not proportional to the extent of local destruction.
Ultimately, neoplastic extension along the entire glans and shaft, invasion of the corpora cavernosa, erosion of the prepuce, bleeding, fistulas, or total destruction of the penis may occur. Occasionally, inguinal ulceration is the initial complaint because of tumor concealed in a phimotic preputial sac. 
The work-up for carcinoma of the penis begins with direct examination and palpation of the penis and inguinal nodes. Cancer of the penis can infiltrate deeply into local tissues. Ultrasonography or magnetic resonance imaging (MRI) of the penis may be useful in delineating the degree of local infiltration.
A computed tomographic (CT) scan of the pelvis and abdomen can help assess the pelvic and para-aortic nodes. A chest x-ray should be obtained in all patients, and a bone scan should be performed when clinically appropriate. A lymphangiogram is not warranted, as it appears to add little information beyond that provided by clinical examination and CT.
The TNM staging system for penile cancer is shown in Table 1. In the literature, the Jackson system is also used extensively, although it lacks the precision of the TNM system. Table 2 compares the two staging systems.
Surgery for treatment of carcinoma of the penis has ranged from circumcision and local excision to radical penectomy, depending on the extent of the lesion. Most authors recommend a 1.5- to 2-cm margin of resection to prevent local recurrence.[9-11] However, a Moh’s micrographic surgical technique has been described; this procedure may offer a less deforming alternative in selected patients and local control rates up to 86%. Erythroplasia of Queyrat usually is managed by circumcision and topical fluorouracil. Bowen’s disease can be managed by local excision or Moh’s surgery. [2,11]
Most relapses occur within the first 12 to 18 months after penectomy. Thus, close follow-up of these patients is important. Montie recommends performing a physical examination of the inguinal nodes monthly for the first 6 months, bimonthly for the next 6 months, and then quarterly for the next year for higher-risk individuals (ie, those with poorly differentiated histology or invasion of the glans or corpus cavernosum). Inguinal CT scans are obtained every 3 to 4 months for the first year.
For patients who develop penile recurrence after initial partial penectomy, further surgical salvage may be possible. Disease that recurs in the urethra is particularly worrisome. Such disease tends to grow quickly through the corpus spongiosum. When faced with this situation, the surgeon should consider resecting the entire urethra and possibly performing an anterior exenteration.
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