Urethral Cancer Specialists  William Aronson, MD Arie Belldegrun, MD Jean B. deKernion, MD Mark S. Litwin, MD, MPH Allan Pantuck, MD, MS, FACS Robert E. Reiter, MD Christopher Saigal, MD, MPH Robert B. Smith, MD Ongoing Clinical Trials No Current Trials... Related Research Projects No Current Research Projects...

General Information

The urethra is the structure that carries urine, and in men, semen from the body. It is located within the penis (organ for reproduction and urination) in men and in front of the vagina (passageway to the uterus, birth canal) in women. Urethral cancer is rare and is often associated with invasive bladder cancer. It tends to spread (metastasize) to adjacent soft tissue and is often locally advanced when diagnosed.

Types
Different types of urethral cancer develop within different types of cells and in different portions of the urethra. In women, the urethra is lined with squamous cells near the urethral opening and transition cells near the bladder. In men, transitional cells line the proximal portion and squamous cells line the urethra within the penis.

Squamous cell carcinoma develops in flat, scaly surface cells and is the most common type of urethral cancer. Other types include the following:

• Transitional cell carcinoma (develops in surface cells of the urethra)
• Adenocarcinoma (develops in glands located near the urethra)
• Melanoma (extremely rare; develops in pigment-producing skin cells)
• Sarcoma (extremely rare; develops in blood vessels, smooth muscle, and connective tissue)

In women, urethral cancer often spreads to the labia, vagina, and bladder neck. In men, the condition may spread to the tissues of the penis and perineum, the prostate gland, the ligament that surrounds the urethra (urogenital diaphragm), the regional lymph nodes, and the penile and scrotal skin.

Incidence and Prevalence
Urethral cancer is more common in women. It can occur at any age, but the incidence is highest in patients in their 60s.

In men, 80% of cases are squamous cell carcinomas, most of which occur in the urethra at the base of the penis. In women, 60% of cases are squamous cell carcinomas.

Risk Factors and Causes

The cause of urethral cancer is unknown. The primary risk factor is a history of bladder cancer.

Infection with human papillomavirus (HPV) and other sexually transmitted diseases (STDs) is also a risk factor. HPV is a group of more than 70 viruses that are transmitted sexually and cause anogenital warts. Two types of HPV are associated with warts that develop on the mucous membrane of the urethra. Having unprotected sexual intercourse with multiple partners increases the risk for HPV infection.

Additional risk factors include the following:

• Age (over age 60)
• Chronic irritation (from childbirth, sexual intercourse)
• Chronic urinary tract infection (UTI)
• Smoking (increases the risk for bladder cancer, which is a risk factor for urethral cancer)

Signs and Symptoms

Early cancer of the urethra often does not produce symptoms. As the disease progresses, symptoms include the following:

• Blood in the urine (hematuria)
• Diminished urine stream and straining to void (caused by urethral stricture)
• Frequent urination and increased nighttime urination (nocturia)
• Hardening of tissue in the perineum, labia, or penis
• Itching
• Incontinence
• Pain during or after sexual intercourse (dyspareunia)
• Painful urination (dysuria)
• Recurrent urinary tract infections
• Urethral discharge and swelling

Diagnosis

Diagnosis of urethral cancer is made by physical examination and biopsy. The urethra and the bladder are thoroughly examined using a thin, lighted tube (called a cystoscope) that is inserted into the urethra. If a suspicious lesion is located, a small piece of tissue is removed surgically and examined under a microscope for cancer cells. Biopsy is performed under local anesthesia, usually in a physician's office or an outpatient surgical center.

If the biopsy is positive, imaging tests are performed to stage the cancer. These tests include x-ray, ultrasound, computed tomography (CT scan), and magnetic resonance imaging (MRI scan). MRI is the preferred method to evaluate urethral cancer.

Treatment

Treatment for urethral cancer depends on the stage and location of the disease, and the patient's age, sex, and overall health. Options include chemotherapy, radiation, and surgery. Because urethral cancer is often invasive, surgery is the primary method of treatment. Chemotherapy and radiation are often used as adjuvant therapies.

Surgery
Surgical treatment options depend on the stage and location of the cancer. Surgery is usually performed under general anesthesia. Early urethral cancer is treated using fulguration (destruction of cancer cells using high-frequency electric current) and laser therapy (destruction of cancer cells using a narrow beam of intense light).

Procedures performed for advanced cases include the following:

• Removal of the bladder and urethra (cystourethrectomy)
• Removal of part of the penis (partial penectomy)
• Removal of the penis, urethra, and penile root (radical penectomy)
• Removal of the bladder and prostate (cystoprostatectomy)
• Removal of cancerous lymph nodes (lymph node dissection)
• Removal of the bladder, urethra, and vagina (anterior exenteration)

Complications of surgery include the following:

• Adverse reaction to anesthesia
• Bowel obstruction
• Incontinence
• Infection
• Mortality (approx. 1- 2% of cases)
• Recurrence (in approx. 50% of cases)
• Tissue death (necrosis)
• Urethral narrowing (stricture) or abnormal passage (fistula)

External beam radiation usually involves treatment 5 days a week for approximately 6 weeks. Brachytherapy involves surgical implantation of the seeds, which become inactive over time and remain in place.

Side effects of radiation are caused by the destruction of healthy tissue and include the following:

• Abnormal healing resulting in abnormal passage in the urethra (fistula)
• Burning of the skin (similar to sunburn)
• Diarrhea
• Fatigue
• Inflammation of the bladder (cystitis)
• Narrowing of the urethra (stricture; causing urination difficulty)
• Nausea

• Anemia (causing fatigue, weakness)
• Nausea and vomiting
• Loss of appetite (anorexia)
• Hair loss (alopecia)
• Mouth sores
• Increased risk for infection
• Shortness of breath
• Excessive bleeding and bruising

Five-year survival rates for noninvasive urethral cancer treated surgically or with radiation are approximately 60%. Recurrence rates for invasive urethral cancer treated with surgery, chemotherapy, and radiation combined are higher than 50%. Early diagnosis and treatment offers the best chance for cure.

Prevention

Urethral cancer cannot be prevented.

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