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TNM-Stages, Diagnosis and Treatment of Female Urethral Cancer

Urethral cancer is a rare malignant tumor of the urethra, which most commonly occurs in women over 70 years old (Amin and Young, 1997) (Krieg and Hoffman, 1999) (Rajan et al., 1993). Primary urethral carcinoma is defined as the first manifestation at the urethra without further involvement of other parts of the urinary tract. Secondary urethral carcinoma occurs as a recurrence after diagnosis and therapy of bladder carcinoma or carcinoma of the upper urinary tract. EAU Guidelines: Urethral carcinoma. For men, please see the section male urethral cancer.

Epidemiology

Rare, the incidence is 1.5 per million. Half of the patients present with advanced tumor stages.

Etiology of Urethral Carcinoma

Risk factors include chronic inflammation or infection, diverticula, caruncle, papillomas, adenomas, leukoplakia, and bladder cancer.

Pathology of Urethral Carcinoma

Histology:

Most common is urothelial carcinoma (45%), followed by adenocarcinoma (29%) and squamous cell carcinoma (19%). Exceptional: melanoma (Derksen et al., 2013).

Metastasis:

Urethral cancer of the distal urethra spreads into the inguinal lymph nodes and tumors of the proximal urethra spread in the pelvic lymph nodes. The lymph node drainage is variable. Hematogenous metastases occur relatively late in squamous cell carcinomas, in contrast to transitional cell cancer.

TNM Tumor Staging of Female Urethral Carcinoma

T:

Local tumor stage.

• Ta: non-invasive papillary carcinoma.
• Tis: carcinoma in situ, flat high-grade tumor without polarity and without invasion.
• T1: infiltration into the subepithelial connective tissue.
• T2: infiltration into the periurethral muscles.
• T3: infiltration of the anterior vaginal wall and the bladder neck.
• T4: infiltration of neighboring organs.

N:

Regional lymph nodes.

• N0: No lymph node metastases.
• N1: Metastasis in a singular lymph node.
• N2: Metastasis in multiple lymph nodes.

M:

Distant metastases.

• M0: No distant metastasis.
• M1: Distant metastasis.

G:

Grading of adenocarcinoma or squamous cell carcinoma.

• G1: Well differentiated.
• G2: Moderately differentiated.
• G3: Poorly to undifferentiated.

G:

Grading of urothelial carcinoma.

• Low-grade: Well differentiated.
• High-grade: Poorly differentiated.

Signs and Symptoms of Urethral Carcinoma

Urethral bleeding, dysuria, frequency, urinary retention, and palpable tumor or induration on pelvic examination.

Diagnosis of Female Urethral Carcinoma

• Cystoscopy and transurethral biopsy/resection of the tumor.
• Staging for invasive tumors: CT of the abdomen and chest, if necessary, MRI of the pelvis.

Treatment of Female Urethral Cancer

Local excision or resection:

Suitable for well-differentiated, non-invasive urethral tumors.

Complete urethrectomy with closure of the bladder:

Complete urethrectomy with closure of the bladder is an option for invasive tumors without infiltration of the bladder neck. Urinary diversion is possible with suprapubic catheter or, e.g., appendicovesicostomy.

Anterior exenteration with complete urethrectomy:

Radical cystectomy with urethrectomy and resection of the anterior vaginal wall are treatment options for invasive tumors. Only a heterotopic urinary diversion is possible.

Lymphadenectomy:

Lymphadenectomy is indicated for invasive tumors and is performed comparable to bladder carcinoma. In the case of distal invasive urethral cancer, inguinal lymphadenectomy is also necessary.

Neoadjuvant chemotherapy:

Trials for urethral carcinoma are not available. Options for neoadjuvant therapy exist by analogy in patients with urothelial carcinoma or squamous cell carcinoma of the bladder.

Radiochemotherapy:

Especially for squamous cell carcinoma, neoadjuvant radiochemotherapy leads to a high response rate (80%); some authors even refrain from curative resection (Kent et al., 2015). Adjuvant radiochemotherapy after curative resection of advanced tumors is also a therapeutic option, especially for patients with positive surgical margins or lymph node metastases.

Chemotherapy for metastatic urethral carcinoma:

Trials for urethral carcinoma are not available. By analogy, the choice of chemotherapy is based on the underlying histology; see also section chemotherapy of metastatic bladder carcinoma.

References

Amin und Young 1997 AMIN, M. B. ; YOUNG, R. H.: Primary carcinomas of the urethra.
In: Semin Diagn Pathol
14 (1997), Nr. 2, S. 147–60

Derksen, J. W.; Visser, O.; de la Rivière, G. B.; Meuleman, E. J.; Heldeweg, E. A. & Lagerveld, B. W. Primary urethral carcinoma in females: an epidemiologic study on demographical factors, histological types, tumour stage and survival.
World journal of urology, 2013, 31, 147-153

Kent, M.; Zinman, L.; Girshovich, L.; Sands, J. & Vanni, A. Combined chemoradiation as primary treatment for invasive male urethral cancer.
The Journal of urology, 2015, 193, 532-537.

G. Gakis, H. M. Bruins, and Comp&eacute, “EAU Guidelines: Primary Urethral Carcinoma,” 2022. [Online]. Available: https://uroweb.org/guidelines/primary-urethral-carcinoma/.

Krieg und Hoffman 1999 KRIEG, R. ; HOFFMAN, R.: Current management of unusual genitourinary cancers. Part 2: Urethral cancer.
In: Oncology (Williston Park)
13 (1999), Nr. 11, S. 1511–7, 1520; discussion 1523–4

Rajan u.a. 1993 RAJAN, N. ; TUCCI, P. ; MALLOUH, C. ; CHOUDHURY, M.: Carcinoma in female urethral diverticulum: case reports and review of management.
In: J Urol
150 (1993), Nr. 6, S. 1911–4

  Deutsche Version: Harnröhrenkarzinom der Frau