Urethral Cancer: Basics of Diagnosis, Staging and Treatment

The urethra is a tube that connects the urinary bladder to the urinary meatus for the removal of fluids from the body.  Urethral cancers grow from the lining of the urethra.  Urethral cancers are rare in both men and women, although they have slightly different epidemiology and etiology depending on sex.  The diagnosis and staging of disease is similar among men and women, however the treatment can be dramatically different.  This blog will review the basics of urethral cancer.

Clinical Presentation

The ratio of male-to-female urethral cancers is believed to be 2:1.[1]  Differences in presentation between men and women are demonstrated in Table 1.

Male Urethral Cancer

Typically presents in middle-aged men in their 40's or later.    Upwards of 50% present with urethral stricture disease and 25% have a history of sexually transmitted infection -- HPV (human papilloma virus) 16 plays a role in the formation of SCC (squamous cell carcinoma) of the urethra.  Greater than 95% of men are symptomatic with symptoms including: urethral bleeding, palpable urethral mass or obstructive voiding.  The symptoms are often slowly progressive, starting with minor symptoms and progressing to major problems -- making early diagnosis a challenge.

Female Urethral Cancer

Urethral cancer is even more rare in women and usually affects women in their 40-50's.  The list of etiologies or related-factors is larger for women and includes: leukoplakia, chronic irritation, caruncles, polyps, parturition, viral infection (HPV) and urethral diverticula (5%) may be related to adenocarcinoma.  Similar to men, >95% of women are symptomatic at presentation with symptoms including: obstructive symptoms (urinary retention is rare in women and malignancy should always be considered in this circumstance), dysuria, urethral bleeding, urinary frequency and/or a palpable urethral mass.

Table 1.

Histology and Pathology 

Urethral cancers are usually urothelial cancers (TCC, transitional cell cancer), SCC or rarely adenocarcinoma.  The prevalence of disease and histology varies by sex and location of tumor.

Male Urethral Cancer

Overall, 80% of urethral cancers in men are SCC with urothelial cancer (15%) and adenocarcinoma (5%) rounding out the remainder of tumors.  Proximal tumors in men are most likely to be urothelial in origin, with rates of SCC increasing with distance from the bulbar urethra (Figure 1).

Figure 1.  Adapted from Cambell-Walsh Urology.

Female Urethral Cancer

In women, 50-70% of urethral cancers are SCC with adenocarcinoma being the second most common tumor type (25%) and urothelial cancer being the most rare (10%).  Histology does not vary by location as it does in men.  Several historical studies indicate that urethral diverticuli have an increased incidence of adenocarcinoma.[2,3]

Figure 2.  Adapted from Cambell-Walsh Urology.

Patterns of Spread

Urethral cancers can be locally invasive and spread into the soft tissues surrounding the urethra.

Male Urethral Cancer

Patterns of lymphatic spread are analagous for male and
female urethral cancer: anterior tumors drain to the
superficial and deep inguinal lymph nodes, posterior
tumors drain to the pelvic lymph nodes.

Local invasion can occur through the spongy tissues of the penis or the corporal bodies.  Tumors that originate in the anterior urethra disseminate through the superificial and deep inguinal lymph nodes, occasionally to the external iliac lymph nodes in the pelvis.  Tumors of the posterior urethra disseminate through the pelvic lymphatic channels, similar to urothelial carcinoma of the bladder.  In men, palpable lymph nodes are present in approximately 20% of patients and always represent metastatic disease (as opposed to penile cancer where these nodes can be inflammatory in nature).

Female Urethral Cancer

Urethral cancers of the female urethra can grow directly into the vulva (skin) of the external genitalia, or when more proximal, invade into the vagina or bladder.  Analagous to male drainage patterns, tumors of the anterior urethra (and labia) drain to the superficial and deep inguinal lymph nodes while tumors of the posterior urethra drain to the external and internal iliac lymph nodes.  Similar to men, most palpable nodes (90%) are malignant.

Diagnosis, Evaluation and Staging

Diagnosis, Evaluation and Staging are identical for men and women and should include:

• Exam under anesthesia
• Cystoscopy
• Bimanual examination
• External genitalia
• Urethra
• Rectum
• Perineum
• Transurethral or needle biopsy
• Cytology is NOT reliable for SCC
• Imaging: CT or MRI
• Abdomen, pelvis to include the genitals and inguinal region.
• Chest radiography

Staging follows the TNM System and prognosis is based on the depth of invasion and presence of lymphatic or distant metastases.

Primary Tumor (T)

TX: cannot be assessed

T0: no evidence of tumor

Ta: Noninvasive papillary, polypoid, or verrucous carcinoma

Tis: carcinoma in situ

T1: Tumor invades subepithelial connective tissue

T2: Tumor invades any of the following: corpus spongiosum (male), prostate (male), periurethral muscle

T3: Tumor invades any of the following: corpus cavernosum (male), beyond prostatic capsule (male), anterior vagina (female), bladder neck

T4: Tumor invades other adjacent organs

Regional Lymph Nodes (N)

NX: Regional lymph nodes cannot be assessed

N0: No regional lymph node metastasis

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

N2: Metastasis in a single lymph node, more than 2 cm but less than 5 cm in greatest dimension; or in multiple nodes, none greater than 5 cm

N3: Metastasis in a lymph node greater than 5 cm in greatest dimension

Distant Metastases (M)

MX: cannot be assessed

M0: no distant metastases

M1: distant metastases

Treatment and Prognosis will be addressed in later blogs.

Summary

• While epidemiology, etiology and treatment of male and female urethral cancer is different, the evaluation and staging are very similar.
• SCC is the most common histology in both men (80%) and women (50-70%).
• 20-33% of patients will have positive lymph nodes at presentation.
• ≥90% of palpable nodes are malignant.
• The anterior urethra drains to inguinal nodes, posterior urethra to pelvic nodes.
• Evaluation should involve:
• Thorough physical examination
• Cystoscopy and biopsy
• Adequate staging by imaging (CT or MRI) +/- chest imaging
• Staging is identical for male and female urethral cancers.

REFERENCES
Sharp, Angermeier.  Surgery of Penile and Urethral Carcinoma.  In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, Novick AC, editors. Campbell-Walsh Urology. 10th ed. Philadelphia: Elsevier; 2012. chapter 35, Pages 934-955.  Eds, Wein, Kavoussi, Novick, Partin and Peters.  

[1] Swartz MA, Porter MP, Lin DW,et al: Incidence of primary urethral carcinoma in the United States. Urology 2006; 68: 1164-1168.
[2] Gheiler EL, Tefilli MV, Tiguert R,et al: Management of primary urethral cancer. Urology 1998; 52: 487-493.
[3] Rajan N, Tucci P, Mallouh C,et al: Carcinoma in female urethral diverticulum: case reports and review of management. J Urol 1993; 150: 1911-1914