Urethra and Penis

FEMALE URETHRA

Carcinoma of the urethra in women is rare; approximately 1,600 cases have been reported in the literature.

Anatomy

The female urethra is approximately 4.0 cm long and extends from the urinary bladder through the urogenital diaphragm to the vestibule, where it forms the urethral meatus.
The lymphatic drainage of the urethral meatus parallels that of the vulva to the superficial and deep inguinal and external iliac lymph nodes. The primary drainage of the entire urethra is mainly to the obturator and internal and external iliac nodes.

Clinical Presentation

A tumor of the urethral meatus at an early stage may resemble a urethral caruncle or a prolapse of the mucosa through the urethral orifice. As the lesion progresses, it enlarges and eventually ulcerates.
Advanced tumors (stages II and III) of the urethra have been associated with a 35% to 50% incidence of inguinal or pelvic lymph node involvement (10).

Diagnostic Workup

A routine history and general physical examination should be performed in all patients.
A detailed pelvic examination under anesthesia is necessary to fully evaluate the clinical extent of the disease. It can be performed at the time of urethroscopy and cystoscopy.
Routine radiographic evaluation should include chest radiographs, an intravenous urogram, and a computed tomography (CT) scan of the abdomen and pelvis.

Staging Systems

Urethral tumors can be classified as those involving the distal half of the urethra and those located in the proximal or entire urethra. Most authors have found that this classification correctly depicts the feasibility of treatment and the prognosis.
The tumor-node-metastasis staging system of the American Joint Committee on Cancer (2) is shown in Table 34-1.

Prognostic Factors

Tumor size and location are the most important factors in determining prognosis and survival.
Eighty-one percent of patients with lesions less than 2 cm had 5-year progression-free survival, compared with 37% of those with lesions 2 to 4 cm and 7% of patients with lesions greater than 4 cm (p = 0.0001) (15).
Bladder neck involvement, parametrial extension, and inguinal lymph node involvement are poor prognostic factors.

TABLE 34-1 AJCC Staging Tables for Urethra and Penis

*AJCC Staging System for Carcinoma of the Urethra*^a
*Primary Tumor (T) (Male and Female)*
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 any of the following: corpus spongiosum, prostate, periurethral muscle
T3	Tumor invades any of the following: corpus cavernosum, beyond prostatic capsule, anterior vagina, bladder neck
T4	Tumor invades other adjacent organs
*Urothelial (Transitional Cell) Carcinoma of the Prostate*
Tis pu	Carcinoma in situ, involvement of the prostatic urethra
Tis pd	Carcinoma in situ, involvement of the prostatic ducts
T1	Tumor invades urethral subepithelial connective tissue
T2	Tumor invades any of the following: prostatic stroma, corpus spongiosum, periurethral muscle
T3	Tumor invades any of the following: corpus cavernosum, beyond prostatic capsule, bladder neck (extraprostatic extension)
T4	Tumor invades other adjacent organs (invasion of the bladder)
*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 node more than 2 cm in greatest dimension, or in multiple nodes
*Distant Metastasis (M)*
MO	No distant metastasis (no pathologic M0; use clinical M to complete stage group)
M1	Distant metastasis
*Stage Grouping*
Stage 0a	Ta	N0	M0
Stage 0is	Tis, Tis pu, Tis pd	N0	M0
Stage I	T1	NO	MO
Stage II	T2	NO	MO
Stage III	T1	N1	MO
	T2	N1	MO
	T3	NO or N1	MO
Stage IV	T4	NO	MO
	T4	N1	MO
	Any T	N2	MO
	Any T	Any N	M1
*Primary Tumor*
TX	Primary tumor cannot be assessed
TO	No evidence of primary tumor
Tis	Carcinoma in situ
Ta	Noninvasive verrucous carcinoma^b
T1a	Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3-4)
T1b	Tumor invades subepithelial connective tissue with LVI or is poorly differentiated
T2	Tumor invades corpus spongiosum or cavernosum
T3	Tumor invades urethra
T4	Tumor invades other adjacent structures
*Regional Lymph Nodes (N)*
NX	Regional lymph nodes cannot be assessed^c
pNX	Regional lymph nodes cannot be assessed^d
NO	No palpable or visibly enlarged inguinal lymph nodes^c
pNO	No regional lymph node metastasis^d
N1	Palpable mobile unilateral inguinal lymph node^c
pN1	Metastasis in a single inguinal lymph node^d
N2	Palpable mobile multiple or bilateral inguinal lymph nodes^c
pN2	Metastasis in multiple or bilateral inguinal lymph nodes^d
N3	Palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral^c
pN3	Extranodal extension of lymph node metastasis or pelvic lymph node (s) unilateral or bilateral^d
*Distant Metastasis (M)*
MO	No distant metastasis (no pathologic MO; use clinical M to complete stage group)
M1	Distant metastasis^e
*Stage grouping*
Stage 0	Tis NO	MO
	Ta NO	MO
Stage I	T1a NO	MO
Stage II	T1b NO	MO
	T2,3 NO	MO
Stage IIIa	T1-3 N1	MO
Stage IIIb	T1-3 N2	MO
Stage IV	T4 Any N	MO
	Any T N3	MO
	Any T Any N	M1
^aStaging from Edge SB, Byrd, DR, Compton CC, et al., eds. AJCC cancer staging manual, 7th ed. New York, NY: Springer Verlag, 2009, with permission. ^bBroad pushing penetration (invasion) is permitted—destructive invasion is against this diagnosis. ^cBased upon palpation, imaging. ^dBased upon biopsy, or surgical excision. ^eLymph node metastasis outside of the true pelvis in addition to visceral or bone sites.

General Management

Anterior Urethral Cancer

Open excision, electroexcision, fulguration, or laser coagulation can be used to treat tumors at the meatus or in situ involvement of the distal urethra (stage 0).
For larger and more invasive lesions (stage I), interstitial irradiation or combined interstitial and external-beam irradiation are alternatives to surgical resection of the distal third of the urethra.
Anterior urethral lesions that recur after treatment by local excision or radiation therapy may require anterior exenteration and urinary diversion.
If no inguinal adenopathy exists, node dissection is not recommended, but prophylactic groin irradiation is recommended for patients with invasive lesions (15).

Posterior Urethral Cancer

Cancers of the posterior or entire urethra (stages II, III, and IV) are usually associated with invasion of the bladder and a high incidence of inguinal and pelvic lymph node metastases.
The best results have been achieved with preoperative irradiation with exenterative surgery and urinary diversion.
A report on 97 patients with urethral carcinoma who were treated using radiotherapy either in the adjuvant or the definitive setting showed 5- and 10-year survival rates of 41% and 31% respectively. Five-year local control was 64%. Forty-nine percent of those who achieved local control developed complications including urethral stenosis, fistula, necrosis, hemorrhage, or cystitis (13).

Radiation Therapy Techniques

Interstitial implant is the usual method for treating meatal carcinomas. Radioactive needles forming a double-plane or a volume implant have been used. After radiographs are used to verify needle placement, a dose of 60 to 70 Gy with low-dose rate (LDR) brachytherapy can be given in 6 to 7 days (0.4 Gy per hour to the target volume) when an implant alone is used.
Large tumors extending into the labia, vagina, entire urethra, or base of the bladder cannot be treated with an implant alone. A combination of external-beam irradiation and implant is recommended (23). The external-beam portal should flash the perineum to cover the entire urethra. The portal should be wide enough to cover the inguinal nodes (11) and extend cephalad to the L5-S1 interspace to include the pelvic nodes. A bolus, appropriate for the photon energy used, should be added to the groins when inguinal nodes are positive. The whole pelvis is treated to a dose of 50 Gy. A boost of 10 to 15 Gy is delivered to positive nodes through reduced anterior photon or en face electron fields (16).
For advanced disease, the primary tumor is treated with a vaginal cylinder to bring the dose to the entire urethra to approximately 60 Gy. An interstitial implant is used to raise the total tumor dose to 70 to 80 Gy LDR brachytherapy. Intracavitary irradiation simultaneously with a vaginal cylinder and an interstitial implant should be used with caution because of the resultant high dose rate at the vaginal mucosa interface of the intracavitary and interstitial implants (16).
A limiting factor in the use of external-beam irradiation is the tolerance of the perineal skin (confluent moist desquamation).

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