Guidelines Summary
The following organizations have released guidelines for the management of urethral carcinomas:
-
National Comprehensive Cancer Network (NCCN)
-
European Association of Urology (EAU)
Diagnosis
NCCN guidelines recommend referral to a specialized center and require the following for a diagnosis [22] :
-
Cystourethroscopy, including exam under anesthesia and transurethral resection or transvaginal biopsy
-
Chest CT (preferred) or PA and lateral chest x-ray
-
Consider abdominal CT or MRI in high-risk T1 disease or patients with ≥T2 disease
-
MRI of pelvis without and with intravenous contrast
If palpable inguinal lymph nodes are present, a chest/abdominal/pelvic CT scan and lymph node biopsy should be performed. [22]
Similarly, the EAU recommends the following for diagnostic evaluation and staging [10] :
-
Urethrocystoscopy with biopsy and urinary cytology
-
CT of the thorax and abdomen/pelvis to assess for distant metastases
-
Pelvic MRI to assess the local extent of urethral tumor and regional lymph node enlargement
Treatment
Tis, Ta, T1:
-
NCCN guidelines recommend repeat of transurethral resection followed by intraurethral bacillus Calmette-Guerin (BCG) therapy in selected cases. [22]
T2-Women:
-
NCCN guidelines recommend either chemoradiotherapy or urethrectomy and cystectomy or distal urethrectomy (depending on tumor location). [22]
T2-Men
NCCN treatment recommendations are summarized as follows [22] :
-
Pendulous urethra: Distal urethrectomy or partial penectomy; if positive margins are present, additional surgery, chemoradiotherapy (preferred), or RT
-
Bulbar urethra: Urethrectomy with or without cystoprostatectomy
-
pT3/pT4, pN1, pN2 disease: Chemotherapy or chemoradiotherapy
T3/T4
NCCN guidelines recommendations are summarized below. [22]
For patients with regional lymph nodes staged cN0, either:
-
Chemoradiotherapy (preferred) with or without consolidative surgery
-
Neoadjuvant chemotherapy and consolidation with surgery or RT
-
RT
-
Surgery alone for non-urothelial histology
For patients with regional lymph nodes staged cN1/cN2, either:
-
RT with chemotherapy (preferred for squamous cell carcinoma)
-
Systemic therapy with or without consolidative surgery
-
Chemoradiotherapy followed by consideration of consolidation with surgery
Localized primary urethral carcinoma in males
EAU recommendations are as follows [10] :
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Offer distal urethrectomy as an alternative to penile amputation for distal urethral tumors, if surgical margins are negative.
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Ensure complete circumferential assessment of the proximal urethral margin if penis-preserving surgery is intended.
Localized urethral carcinoma in females
EAU recommendations are as follows [10] :
-
Offer urethra-sparing surgery as an alternative to primary urethrectomy for distal urethral tumors, if negative surgical margins can be achieved intraoperatively.
-
Offer local radiotherapy as an alternative to urethral surgery, but discuss local toxicity.
Advanced urethral carcinoma in males and females
EAU recommendations are as follows [10] :
-
Discuss the treatment of patients with locally advanced urethral carcinoma within a multidisciplinary team of urologists, radio-oncologists, and oncologists.
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In locally advanced urethral carcinoma, use cisplatin-based chemotherapeutic regimens with curative intent prior to surgery.
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In locally advanced squamous cell carcinoma of the urethra, offer the combination of curative RT with radiosensitizing chemotherapy for definitive treatment and genital preservation.
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Offer salvage surgery or RT to patients with urethral recurrence after primary treatment.
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Offer inguinal lymph node dissection to patients with limited LN-positive urethral squamous cell carcinoma.
Distant metastasis
NCCN guidelines recommend systemic therapy (chemotherapy or checkpoint inhibitors as subsequent-line therapy). [22]
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Male urethral anatomy from most proximal to distal. Shown is the prostatic urethra (from bladder neck to the urogenital diaphragm [UGD]), membranous urethra (traversing the UGD), bulbous urethra (from the UGD to the penoscrotal junction), and the penile or pendulous urethra (from the penoscrotal junction traversing distally) with its boat-shaped most distal aspect, the fossa navicularis. Note the adjacent structures of the corpus cavernosum, bladder, prostate, pubic symphysis, perineum, and scrotum, which are sites of local extension and often are excised en bloc.
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(A) Normal anatomy. Sagittal T2-weighted image labelling the prostatic, membranous, and bulbous segments of the normal male urethra. (B) Normal anatomy. Illustration of the normal female urethra in axial cross-section. (C) Normal anatomy. Axial T2-weighted image of a normal female urethra. Note the hypointense signal of the mucosa and outer muscular layer and hyperintense submucosa. Image used with permission from Del Gaizo A et al, Magnetic resonance imaging of solid urethral and peri-urethral lesions. Insights Imaging. Aug 2013;4(4):461-9. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731464/.
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Illustration of the male urethra in the sagittal plane highlighting the percentage of urethral carcinoma by location (1st percentage) and the most common histological subtype in that location (2nd percentage). TCC = transitional cell carcinoma, SCC = squamous cell carcinoma. Image used with permission from Del Gaizo A et al, Magnetic resonance imaging of solid urethral and peri-urethral lesions. Insights Imaging. Aug 2013;4(4):461-9. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731464/.
Tables
Primary tumor (T) |
|
Male penile urethra and female urethra |
|
TX |
Primary tumor cannot be assessed |
T0 |
No evidence of primary tumor |
Ta |
Noninvasive papillary carcinoma |
Tis |
Carcinoma in situ |
T1 |
Tumor invades subepithelial connective tissue |
T2 |
Tumor invades the corpus spongiosum or periurethral muscle |
T3 |
Tumor invades the corpus cavernosum or anterior vagina |
T4 |
Tumor invades other adjacent organs (eg, bladder wall) |
Prostatic urethra |
|
TX |
Primary tumor cannot be assessed |
T0 |
No evidence of primary tumor |
Ta |
Noninvasive papillary carcinoma |
Tis |
Carcinoma in situ involving the prostatic urethra or periurethral or prostatic ducts without stromal invasion |
T1 |
Tumor invades urethral subepithelial connective tissue immediately underlying the urothelium |
T2 |
Tumor invades the prostatic stroma surrounding ducts either by direct extension from the urothelial surface or by invasion from prostatic ducts |
T3 |
Tumor invades the periprostatic fat |
T4 |
Tumor invades other adjacent organs (ie, extraprostatic invasion of the bladder wall, rectal wall) |
Regional lymph nodes (N) |
|
NX |
Regional lymph nodes cannot be assessed |
N0 |
No regional lymph node metastasis |
N1 |
Single regional lymph node metastasis in the inguinal region or true pelvis or presacral lymph node |
N2 |
Multiple lymph node metastases in the inguinal region or true pelvis or presacral lymph node |
Distant metastasis (M) |
|
MX |
Distant metastasis cannot be assessed |
MO |
No distant metastasis |
M1 |
Distant metastasis |
Stage |
T |
N |
M |
Stage 0a |
Ta |
N0 |
M0 |
Stage 0is |
Tis |
N0 |
M0 |
Stage I |
T1 |
N0 |
M0 |
Stage II |
T2 |
N0 |
M0 |
Stage III |
T1 |
N1 |
M0 |
T2 |
N1 |
M0 |
|
T3 |
N0 |
M0 |
|
T3 |
N1 |
M0 |
|
Stage IV |
T4 |
N1 |
M0 |
Any T |
N2 |
M0 |
|
Any T |
Any N |
M1 |
