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Urethral cancer
Background
Overview
Definition
Urethral cancer is a rare malignancy originating from the epithelial cells of the urethra, with histological types including SCC, transitional cell carcinoma, and adenocarcinoma.
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Pathophysiology
The pathogenesis of urethral cancer involves the malignant transformation of urethral epithelial cells, often preceded by dysplastic changes. SCC is more common in the distal urethra, while transitional cell carcinoma typically arises in the proximal urethra. The tumor can invade adjacent tissues, including the bladder, vagina, or prostate.
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Epidemiology
The incidence of primary urethral carcinoma in the US is estimated at 4.3 per million in males and 1.5 per million in females, with a higher incidence observed in the elderly and African Americans.
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Risk factors
Chronic inflammation of the urethra, such as recurrent UTIs and urethral strictures, is a recognized risk factor for urethral cancer. HPV 16 infection, STIs, and prolonged catheter use are also risk factors for urethral cancer.
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Disease course
Clinical manifestations of urethral cancer vary according to tumor location and size. Common symptoms include hematuria, urethral bleeding, dysuria, and obstructive symptoms. A palpable urethral mass, perineal pain, and discharge may also be present. Advanced disease can present with pelvic pain, weight loss, and symptoms related to metastasis.
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Prognosis and risk of recurrence
The prognosis of urethral cancer is generally poor, largely due to late diagnosis and high rates of local recurrence and metastasis. Early-stage disease has a better prognosis, with localized tumors amenable to surgical resection. Advanced or metastatic disease carries a poorer prognosis.
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Guidelines
Key sources
The following summarized guidelines for the evaluation and management of urethral cancer are prepared by our editorial team based on guidelines from the European Association of Urology (EAU 2025) and the American Urological Association (AUA 2023).
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Classification and risk stratification
Staging: as per EAU 2025 guidelines, use the 2017 TNM classification and 2022 WHO grading system for pathological staging and grading of primary urethral carcinoma.
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TNM classification for primary urethral carcinoma
Tumor classification
Tx: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
Ta: Noninvasive papillary, polypoid, or verrucous carcinoma
T1. Tumor invading subepithelial connective tissue
T2: Tumor invading corpus spongiosum, prostate, or periurethral muscle
T3: Tumor invading corpus cavernosum, beyond prostatic capsule, anterior vagina, or bladder neck (extraprostatic extension)
T4: Tumor invading other adjacent organs (invasion of the bladder)
Lymph node classification
Nx: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single lymph node
N2: Metastasis in multiple lymph nodes
Metastasis classification
M0: No distant metastasis
M1: Distant metastasis present
Stage cannot be fully assessed
Diagnostic investigations
Diagnostic procedures
Medical management
Management of localized disease, males
As per EAU 2025 guidelines:
Offer distal urethrectomy as an alternative to penile amputation in male patients with localized distal urethral tumors, if negative surgical margins can be achieved intraoperatively.
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Ensure complete circumferential assessment of the proximal urethral margin if penile-preserving surgery is intended.
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Management of localized disease (females)
Management of locally advanced disease
Specific circumstances
Patients with urothelial carcinoma of the prostate
As per EAU 2025 guidelines:
Offer a urethra-sparing approach with transurethral resection and BCG in patients with noninvasive urethral carcinoma or carcinoma in situ of the prostatic urethra and prostatic ducts.
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Perform cystoprostatectomy with extended pelvic lymphadenectomy in patients not responding to BCG or in patients with extensive ductal or stromal involvement.
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