Urethral cancer is an extremely rare lesion, with only approximately 600 reported cases. Urethral cancer comprises less than 1% of the total incidence of malignancies. Because many medical centers see only a few cases over many years, not enough data are available from large series to dictate the best-accepted treatment.
As with most tumors, early detection affords the best chance of cure. Once invasive cancer is detected, radical surgery is indicated, although the prognosis usually is poor.
History of the Procedure: Urethral carcinoma has certain anatomic and histologic considerations, particularly concerning the differences between the male and female urethra and the respective adjacent structures. In general, however, in both males and females, urethral cancer possesses a tendency to invade locally and to metastasize to adjacent soft tissues. Therefore, most of these tumors are locally advanced at the time of diagnosis, reflecting the generally poor prognosis despite aggressive treatment. Urethral cancer rarely metastasizes to distant loci. Only 14% of female patients with urethral cancer have evidence of metastatic spread.
Problem: Anatomic and histologic considerations exist among cases of urethral cancer because of the uniqueness of the urethra between males and females. The long male urethra is divided into anterior and posterior components, while the female urethra is approximately 3 cm in length and does not require subdivisions. In both the male and female urethra, the histologic pattern of the urethral mucous membrane progresses from transitional epithelium to squamous epithelium as it continues distally. These mucosal cells are what histologically classify urethral cancer as squamous-cell cancer, transitional-cell carcinoma, or even adenocarcinoma because transitional cells can undergo adenomatous metaplasia.
In females, the most common sites of tumor invasion are the labia, vagina, and bladder neck. In males, the most common sites of extension are the vascular spaces of the corpora and periurethral tissues, the deep tissues of the perineum, the urogenital diaphragm, the prostate, and the penile and scrotal skin, where it causes abscesses and fistulae.
Frequency: Again, this is a rare tumor, with only approximately 600 reported cases. In both males and females, the most common type of urethral malignancy is squamous-cell cancer. In men, these lesions comprise 78% of the total cases and occur primarily in the bulbomembranous and penile regions.
Transitional-cell carcinoma is the second most common urethral malignancy in both sexes. In males, this lesion accounts for 15% of total cases and occurs in the prostatic urethra.
Cancers of the meatus and permeatus are rare because the papillomas and condylomata rarely transform into malignant clones. Likewise, melanoma of the urethra is reported in the literature but is clinically rare.
Race: Urethral cancer is more common in whites than in blacks; however, blacks have a worse prognosis after diagnosis.
Sex: Urethral cancer is the only genitourinary malignancy that is more common in females than in males. This finding is surprising considering the complexity and length of the male urethra.
Age: Urethral cancer has been reported within an age range of 13-90 years, thus occurring at any age; however, it is observed most commonly during the seventh decade.
Etiology: The etiology of urethral cancer is obscure. Although cigarette smoking, exposure to aromatic amines, and analgesic abuse are associated with transitional-cell carcinoma of the bladder, no such correlation exists with urethral carcinoma. Patients with a history of bladder cancer have an increased risk of urethral cancer.
Various studies cite infection and chronic irritation as etiologic agents in the tumorigenesis of this malignancy.
Kaplan and Grayhack found that 37% of males with urethral cancer had some history of venereal disease.
Ray et al found a 44% concordance of patients with urethral cancer and a history of sexually transmitted diseases. In addition, human papilloma virus (HPV) recently was associated with urethral cancer.
Chronic inflammation as an etiology of urethral cancer is highly controversial. One study found that 88% of male patients with urethral cancer had a history of stricture; another study found the correlation in only 16% of patients.
No such associations have been established in females, although chronic irritations from parturition, coitus, and infection have been proposed as etiologic agents.
Pathophysiology: Chronic inflammation, infection, or irritation of the urethra usually precedes the development of urethral cancer. Rapid turnover of the urethral mucosal cells predisposes to the development of dysplasia and neoplasia. Inflammation, infection, and irritation may impede the natural DNA repair mechanisms of the urethral mucosal cells. The tumor develops and invades deeply in order to metastasize to adjacent structures. The tumor thus becomes elusive to definitive therapies such as surgery and radiation.
Clinical: The signs and symptoms of urethral cancer vary and are neither diagnostic nor pathognomonic. Generally, the onset is insidious, and symptoms usually are more attributable to benign stricture disease (ie, bladder outlet obstruction, overflow incontinence), rather than malignancy (ie, perineal pain, hematuria). In fact, in both sexes, the cancer may be completely asymptomatic.
The interval between the onset of symptoms and diagnosis may be as long as 3 years because of misdiagnoses and failure by the patient to seek medical consultation. Remember that these tumors have a propensity to be highly advanced locally at the time of diagnosis. A raised index of suspicion is advisable if an elderly man presents with stricture disease, particularly if symptoms are present that are more consistent with malignancy or local extension (ie, urethral fistulae, necrosis and abscess formation).
Early evaluation should include cytologic analysis, imaging, and endoscopic management with biopsy of the strictured area, particularly if it appears abnormal (ie, irregular borders, erythema, macular or papular appearance, surface ulceration and tissue sloughing). This is in contrast to benign urethral stricture disease (USD), which generally appears as smooth gray-white areas of spongiofibrosis.
Symptoms
• Diminished stream, straining to void, and other obstructive voiding symptoms (Although these often are the symptoms of benign stricture disease, a neoplasm may be concealed by the presentation of a routine stricture. Keep a high index of suspicion in patients with a history of USD, and keep a vigilant eye over the proceeding cytological analysis, radiographic imaging, and cystoscopy.)
• Frequency, nocturia, itching, dysuria, and other irritative voiding symptoms (These are reported notoriously in association with carcinoma in situ.)
• Incontinence (Generally, this is overflow incontinence from bladder outlet obstruction due to USD. However, severe urgency may progress to urge incontinence and distortion of the urethral anatomy in females and may lead to stress urinary incontinence.)
• Urinary retention from progressive USD
• Hematuria, urethral or vaginal spotting
• May produce no symptoms except a hard nodular area in the perineum, labia, or along the course of the penis
• Purulent, foul-smelling, or watery discharge
• Hematospermia
• Perineal, suprapubic, or urethral pain
• Dyspareunia
• Swelling
• Tenesmus
Signs and physical examination findings
• Urethral-cutaneous fistula
• Urethral-vaginal fistula
• Urethral diverticula
• Periurethral abscess or areas of tissue necrosis
• Recurrent urinary tract infection
• Penile or vaginal lesions
• Lymphadenopathy
• Palpable mass along the course of the urethra

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