Urethral Cancer

Urethral cancer is a rare type of cancer affecting the male or female urethra that comprises approximately 1 to 2 percent of all urological cancers. Urethral cancer is the only urological cancer that affects women more frequently than men. To date, the number of persons diagnosed with this condition each year has remained stable. Although some people with urethral cancer do not complain of any symptoms, most do. What are these symptoms? How should this malignancy be treated? What is the chance of recovery? The following information should help answer these questions.

What happens under normal conditions?

The urethra is a hollow tube that allows urine to pass from the bladder, the organ that stores urine until ready for release, to the outside of the body. In men the urethra is approximately eight inches long, and passes through the prostate and the penis before it opens to the outside at the end of the penis. In women the urethra is approximately one and a half inches long and opens to the outside just above the vaginal opening.

A layer of cells called epithelium lines the urethra. In both men and women there are several glands located along the length of the urethra. A supportive network of connective tissue, elastic and muscle fibers and blood vessels surrounds the urethra.

What causes urethral cancer?

The exact cause of urethral cancer is not known. However, chronic inflammation and infection have been identified as factors that may increase the risk for developing this condition. Many men with urethral cancer have previously been treated for urethral stricture disease or sexually transmitted infections (STIs). Many women with urethral cancer have previously been treated for urethral caruncle, urethral diverticulum or chronic urinary tract infection. In both men and women the presence of human papilloma virus (HPV) has been linked to urethral cancer.

What are the symptoms of urethral cancer?

In its early stages, there are usually few symptoms associated with urethral cancer. As the cancer grows, some patients may notice a lump or growth on the urethra. Others may notice pain or bleeding that accompanies urination. If the tumor grows so that it narrows the diameter of the urethra, patients may have difficulty urinating or pass blood from their urethra.

How is urethral cancer diagnosed?

The diagnostic investigation begins with a thorough medical history and physical examination. The urologist will ask the patient about medical conditions that may be associated with urethral cancer, such as urethral stricture, STIs, bladder cancer, urethral caruncle, urethral diverticulum and urinary tract infection. The urologist will examine the urethra, feeling for any abnormalities.

An important diagnostic instrument that the urologist will use is the cystoscope, which is a thin, lighted scope that allows the urologist to view the inside of the urethra. Cystourethroscopy is most commonly performed as an office procedure under local anesthesia. If the urologist observes any abnormalities, the patient will require a biopsy.

A tissue biopsy is essential to diagnose urethral cancer. It is difficult to perform this procedure under local anesthesia, so the patient is usually scheduled to return for biopsy. Under general anesthesia or regional anesthesia, the urologist will biopsy any suspicious areas identified. Certain patients may also require a biopsy technique that involves passing a needle through the skin or vagina into the urethral growth. The biopsy tissue is then sent to the pathologist for examination under a microscope to confirm the diagnosis. Before the patient awakens from anesthesia, the urologist will perform a thorough examination to determine the local extent of the tumor.

Once urethral cancer is found, the extent of disease is categorized (i.e. staged) based on how deeply the tumor has penetrated the tissues surrounding the urethra (Table 1). More tests will be performed to find out if cancer cells have spread to other parts of the body. A CT scan of the abdomen and pelvis may be performed in order to examine the lymph nodes that collect drainage from the urethra. An MRI may be performed in order to examine the local extent of the tumor. A chest X-ray is usually obtained to ensure that the tumor has not spread to the lungs, and select patients may require a bone scan to look for bony metastases. If the urethral cancer is classified as transitional cell carcinoma, the patient will undergo either excretory urography or retrograde pyelography to image the lining of the kidney and ureter to ensure there are no other sites of cancer.

In men, the part of the urethra that is closest to the bladder and prostate is more likely to originate from the cells that line the urinary tract (urothelial or transitional cells), whereas the part of the urethra inside the penis is more likely to originate from cells more like the skin (squamous cells), This difference may impact the way the disease is treated.

How is urethral cancer treated?

There are treatment options for all patients diagnosed with urethral cancer. These options may be divided into three categories: surgery, radiation and chemotherapy. Surgery is the most common treatment for cancer of the urethra. There are several surgical techniques that may be used. For so-called "superficial" cancers, where the tumor has not invaded into surrounding tissues, the tumor may be removed by inserting an instrument such as a cystoscope into the urethra and using a loop electrocautery to remove the tumor, thereby avoiding an incision. For tumors that demonstrated invasion, some patients may require conventional surgery to remove the affected area. Certain men with a tumor that involves only part of the urethra inside the penis (anterior urethra) may require removal of part of the penis that contains the tumor (partial penectomy) or even removal of the entire penis (penectomy). A decision about whether to remove part or all of the penis depends on the location of the tumor and whether the entire tumor can be removed (with an adequate margin of normal tissue (usually 1-2 centimeters) to still allow a man to stand to urinate. In addition, if the tumor is invading into the erectile tissues of the penis itself, the entire penis may need amputation. If this procedure is done, a small hole on the underside of the scrotum is created (perineal urethrostomy) that allows urination. Of course, this procedure results in a situation where the patient must sit to void.

For patients with tumors that involve the part of the urethra that connects to the bladder and prostate (posterior urethra) more extensive surgery may be required. In men with this type of tumor the bladder and prostate, part of the bony pelvis, as well as the penis, may be removed. If this surgery is done, a piece of bowel is utilized to create a pouch into which the kidneys drain. This pouch can either be incontinent (thus, requiring wearing a stoma bag) or continent (requiring that the patient pass a small catheter 3-4 times a day to drain the pouch). Determining which type of reconstruction is right for you depends on what other medical conditions you have and your personal preference and circumstances.

In women with this type of tumor surgery to remove the urethra, bladder and part of the vagina may be required. Because the female urethra is so much shorter than the male urethra, it is rare to have a tumor small enough and distant enough from the urethral continence mechanism (sphincter) to remove the tumor with a margin of normal tissue and maintain urinary continence. Only the outer-most 1/3 (or about 7 mm) of urethra can be removed without compromising the continence mechanism. For this reason, the majority of women diagnosed with urethral cancer undergo removal of the urethra, bladder, and a portion of the vagina and the creation of a pouch with bowel into which the kidneys drain (see above).

For the men and women undergoing these extensive surgeries lymph nodes in the pelvis are often removed as well. When this is done, some patients may experience leg swelling owing to the fact that the lymphatic nodes that are removed are responsible for the drainage of fluid that seeps out of the blood vessels into the legs.

Radiation therapy destroys cancer cells with high-energy radiation. Radiation therapy may be used alone or in conjunction with surgery or chemotherapy. Although radiation therapy may allow the patient to retain his or her urethra and surrounding organs, this method of treatment is not without complications. Radiation to this region can result in bladder irritation, incontinence, or bleeding, rectal (or vaginal in women) pain and bleeding, as well as stricture to the urethra, causing obstructive urinary symptoms.

Chemotherapy kills cancer cells with drugs. Chemotherapy is generally reserved for situations where the cancer has escaped the urethra, so called metastatic tumors. Usually it is utilized either before surgery or radiation or after to help kill cells outside of the area targeted by the surgery or radiation. The type of drugs used for the treatment of each cancer depends on the risk that patient has for having metastasis, the burden of metastatic disease, and the specific histologic subtype of the tumor (urothelial or squamous). Each chemotherapy drug has a different side-effect profile, but most patients are monitored very closely by an oncologist during and after treatment with these drugs to prevent major problems with the medications.

What to expect after treatment?

Despite aggressive therapy with chemotherapy, radiation therapy and surgery, recurrence of urethral cancer following treatment is not uncommon. For this reason, patients with this condition require life-long follow-up with a physician. Follow up generally entails having a physical exam, lab work, CT scan and a chest x-ray on a semi-annual or annual basis. Only with early recognition of recurrence and prompt initiation of appropriate therapy in such cases is prolonged survival possible.

Frequently asked questions:

What determines if urethral cancer can be treated with local excision vs. a more radical surgical procedure?

In general, urethral cancers that involve the anterior urethra (part of the urethra closest to the outside) are more often successfully treated with local surgery. Tumors that involve the posterior urethra (part of the urethra closest to the bladder) often require more radical surgery to ensure optimal outcome.

What are the chances of urethral cancer coming back following treatment?

The likelihood of urethral cancer recurring following treatment depends on both the stage and location of the initial tumor. For patients with low stage disease, the five-year disease specific survival rate approaches 90 percent; patients with high stage disease have a survival rate of 33 percent. For patients with tumor located in the anterior urethra (the portion of the urethra in the penis for men, and the outermost 7-10 mm for women) regardless of stage, the five-year disease specific survival is 60 to 70 percent, whereas for patients with tumor located in the posterior urethra (the area that traverses the prostate in men and the innermost 1.5-2 cm in women) regardless of stage, the five-year survival rate is less than 25 percent.

If my bladder was surgically removed due to bladder cancer, can I still develop urethral cancer?

Yes, patients who undergo cystectomy for bladder cancer may still develop cancer of the urethra. For this reason, it is important for these patients to maintain close follow-up with their urologist. These patients will require periodic cytologic evaluation of urethral washings, and if cancerous cells are found in these washings a urethrectomy may be required.

Table 1 - TNM Staging of Urethral Cancer

Primary Tumor (T)

Tx: Primary tumor cannot be assessed

T0: No evidence of primary tumor

Ta: Noninvasive papillary, polypoid or verrucous carcinoma

Tis: Carcinoma in situ

T1: Tumor invades subepithelial connective tissue

T2: Tumor invades corpus spongiosum, prostate or periurethral muscle

T3: Tumor invades corpus cavernosum, beyond prostatic capsule, anterior vagina or bladder neck

T4: Tumor invades other adjacent organs (i.e. bladder)

Regional Lymph Nodes (N)

Nx: Regional lymph nodes cannot be assessed

N0: No regional lymph node metastasis

N1: Metastases in a single lymph node, 2 cm or less in greatest dimension

N2: Metastases in a single node >2 cm but <5 cm in greatest dimension, or in multiple nodes (none greater than 5cm)

N3: Metastases in lymph node greater than 5 cm in greatest dimension

Distant Metastases (M)

Mx: Distant metastases cannot be assessed

M0: No distant metastases

M1: Distant metastases