Incidence by Age

Primary carcinoma of the male urethra is extremely rare. Although cases have been reported in the literature as young as age 13, the SEER database records no cases in patients younger than the age of 20. The incidence increases with advancing age from 0.1 per 100,000 in patients ages 20 to 34, to a peak incidence of 2.6 per 100,000 in patients older than age 85.²

Etiology

No specific causal factors have been identified. However, chronic inflammation likely plays a role in the development of urethral cancers. Patients diagnosed with urethral cancers often have a history of prior sexually transmitted disease, urethritis, or urethral stricture. The incidence of urethral stricture in men diagnosed with carcinoma of the urethra ranges from 24% to 76%.³ The site of stricture is also the most likely site of malignancy.⁴ Approximately 10% of patients who undergo cystectomy for invasive bladder cancer also develop a urethral cancer distal to the urogenital diaphragm.

Anatomy

The male urethra, composed of a mucosa and submucosa, is approximately 20 cm in length and extends from the neck of the bladder to the external meatus of the glans penis. The prostatic urethra begins at the bladder neck and lies within the prostate. It is usually 3 cm long. It is the widest and most readily dilated portion of the urethra. It typically emerges anterior to the prostatic apex and merges with the membranous urethra. The membranous urethra lies within the urogenital diaphragm surrounded by the sphincter urethrae muscle and is the least dilatable portion of the urethra. The prostatic and membranous urethra are lined with transitional epithelium. The spongy (cavernous) urethra is enclosed in the corpus spongiosum. It is further subdivided into urethra confined by the penile bulb (bulbous urethra) and urethra distal to the bulb (penile or pendulous urethra). The narrowest portion of the urethra is the external meatus. The bulbomembranous urethra is known as the posterior urethra, while the penile urethra is referred to as the anterior urethra. Pseudostratified columnar epithelium lines the bulbous and penile urethra. Stratified squamous epithelium lines the urethra defined by the glans penis (Fig. 47-1). Numerous glands can be found in the submucosa of the urethra.

FIGURE 47-1 • Anatomy of the penis and urethra.

The bulbomembranous urethra is the most common site of primary malignancies (60%). Of these, 30% occur in the penile urethra, and 10% originate in the prostatic urethra.⁵

The anterior urethra drains into the superficial and deep inguinal lymph nodes. The bulbomembranous and prostatic urethra drain into the pelvic lymph nodes. Posterior lesions may drain to the external and internal iliac, obturator, and presacral lymph nodes.⁶

Pathologic Conditions

Transitional cell carcinomas that arise in the prostatic urethra are clinically and histologically similar to those that arise in the bladder. Transitional cell carcinomas that originate in the bladder neck that extend into the urethra may be mistaken for a primary urethral cancer. Of male urethral cancers, 80% are squamous cell carcinomas, and 15% of male urethral cancers are transitional cell carcinomas. Only 5% are either adenocarcinomas, which are thought to arise in the submucosal glandular tissue, or undifferentiated tumors.

Natural History

Primary urethral cancers are often insidious, and symptoms are often present only when the disease is locally advanced.⁷ The most common presenting symptoms include a palpable urethral mass, obstructive urinary symptoms, pain, urethral fistula or abscess, hematuria, or a palpable inguinal mass.⁸ Because many symptoms are not specific, symptoms have been reported to be present on average 5 months before diagnosis (range, 1 day to 15 years).⁹ Urethral carcinoma often directly invades adjacent structures such as the corpus spongiosum and periurethral tissues. Bulbomembranous lesions can extend into the urogenital diaphragm and prostate. Invasion into the corpora cavernosa is common at the time of diagnosis. Hematogenous spread (lung, brain, bone, lymph nodes) is relatively uncommon, except in locally advanced cases.¹⁰

Prognosis of male urethral carcinomas depends primarily on location and the degree of invasion. Anterior superficial lesions generally present earlier and carry the best prognosis, while deeply invasive lesions or those located posteriorly are rarely curable. Posterior lesions tend to be deeply invasive at the time of diagnosis. Histologic findings are thought to be less significant as a prognostic factor.¹¹

Staging

Diagnosis is established with a transurethral biopsy. Urine cytologic examination may also be helpful. The extent of disease is determined by careful inspection and palpation of the external genitalia and perineum as well as cystourethroscopy. Bimanual examination under anesthesia may also be indicated for posteriorly located lesions. Computed tomography (CT) and magnetic resonance imaging (MRI) of the pelvis may help to evaluate the extent of disease and the status of lymph nodes. MRI should be performed whenever possible to document the extent of local soft tissue extension. Positron emission tomography and lymphangiograms may also help in evaluating the true extent of disease.

The tumor-node-metastasis (TNM) staging system set forth by the American Joint Committee on Cancer allows data collected by both physical examination and imaging in the staging of urethral cancers. T staging is determined mainly by the depth of invasion. Regional lymph nodes are considered to be the pelvic and inguinal nodal beds. Laterality does not affect the N status (Table 47-1).¹²

Table 47-1 Classification of Primary Urethral Carcinomas

Rights were not granted to include this table in electronic media. Please refer to the printed book.

Management

The primary modalities of therapy for male urethral carcinomas include surgery, radiation therapy, and chemotherapy.

In most cases, surgery is the primary therapy for urethral carcinomas. Surgical approaches include transurethral resection (TUR), local excision, partial amputation, or radical amputation of the penis. For superficial papillary or in situ disease, TUR and fulguration are deemed adequate therapy. For anterior lesions in the distal half of the penis, a partial resection with 2-cm margins should be attempted. Local recurrences after partial amputation are uncommon. Conservative surgical therapy is generally only considered for solitary, low-grade, low-stage lesions. For invasive lesions in the more proximal portion of the penis, a radical amputation is indicated. If the lesion is extensive and involves the scrotum, emasculation may be necessary. Ilioinguinal lymph node dissection is carried out if the nodes are palpable or appear to be involved on imaging studies (after confirmation in frozen sections). In cases of limited regional lymph node involvement, node dissection may still be curative. In cases in which no lymph node involvement is evident, groin dissection is not indicated, but should still be watched carefully in follow-up visits.

The role of radiation therapy alone for lesions in the distal urethra is not well defined but provides the option of organ preservation. Radiation therapy alone can be curative for distal lesions, with long-term cure rates similar to those reported for surgery. The most common approach uses external-beam radiotherapy with doses between 50 and 75 Gy.¹³

Various techniques for treating male urethral cancers with radiotherapy have been described. The “crossfire” technique, commonly used for distal lesions, involves positioning the penis vertically by suspending it with a Foley catheter and using parallel opposed external-beam fields without bolus. Prophylactic lymph node irradiation is generally not advocated. Prostatic urethra patients can be treated in similar fashion to prostatic adenocarcinomas.

Penile radiotherapy often produces a brisk acute skin reaction and edema. These effects generally subside during a 2- to 4-week period. Skin necrosis or ulceration is uncommon. Significant edema and strictures can develop as a result of radical radiotherapy.

Local control may be more difficult to achieve in the bulbomembranous urethra because these lesions tend to be more locally aggressive (Fig. 47-2). Because metastasis tends to be a late event, aggressive combined approaches to local therapy should be considered.

FIGURE 47-2 • Conformal external-beam radiotherapy for a lesion of the bulbomembranous urethra.

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