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Urethral cancer (cancer of the urethra)
Medical expert of the article
Last reviewed: 12.07.2025
Urethral cancer (urethra cancer) is a rare tumor, accounting for less than 1% of all urinary tract tumors. The low incidence rate means there is no standardized approach to managing patients with urethral cancer.
In this regard, the results of treatment of this disease remain unsatisfactory.
Epidemiology
Primary urethral cancer in men is extremely rare. There are about 600 reports in the literature. The tumor is diagnosed at any age, although men over 50 years of age are more often affected. In women, urethral cancer (cancer of the urethra) accounts for 0.02-0.5% of malignant neoplasms of the female genitourinary system. The disease usually develops in postmenopause. 75% of patients with urethral cancer are over 50 years of age.
Causes urethral cancer (cancer of the urethra).
The etiology of urethral cancer is unknown. An optional precancerous condition is leukoplakia. Risk factors include bladder cancer, chronic urinary tract infection, and long-term trauma to the urethral mucosa.
Histogenesis
The histogenesis of urethral cancer depends on the type of epithelium covering the area of the urethra where the tumor is localized. The distal part of the urethra is lined with squamous epithelium, which is the source of squamous cell carcinoma, the proximal part is covered with transitional epithelium, from which transitional cell tumors originate.
Adenocarcinoma arises from the glandular tissue of the prostate in men and paraurethral glands in women. In women, squamous cell carcinoma accounts for 60%, transitional cell carcinoma - 20%. adenocarcinoma - 10%. melanoma - 2%. rare tumors (sarcomas, neuroendocrine tumor, plasmacytoma, metastases of other tumors) account for 8% of all cases. Among men, tumors of the urethra are represented by squamous cell carcinoma in ox, transitional cell carcinoma - in 15%, adenocarcinoma, melanoma and sarcomas in 5% of cases.
Growth and metastasis
Urethral cancer, especially when its proximal parts are affected, tends to grow locally invasively. In men, it may invade the spongy and cavernous bodies of the penis, urogenital diaphragm, prostate, perineum, and scrotal skin. In women, the tumor tends to invade underlying tissues and spread to the anterior wall of the vagina, bladder, and cervix.
Urethral cancer is characterized by lymphogenous metastasis to the inguinal and iliac lymph nodes. Enlarged inguinal lymph nodes are detected in 1/3 of patients with urethral cancer, and the presence of metastases is confirmed in 90% of cases. At the time of diagnosis, 20% of patients have metastases to the iliac lymph nodes. Subsequently, the appearance of metastases in the pelvic lymph nodes is noted in 15% of patients. Metastasis to distant groups of lymph nodes is rare.
Hematogenous metastases to parenchymatous organs appear late. Cases of damage to the lungs, pleura, liver, bones, adrenal glands, brain, salivary glands, and head of the penis have been described.
Symptoms urethral cancer (cancer of the urethra).
Symptoms of urethral cancer are variable, non-pathognomonic and largely depend on the disease against which the malignant process develops. Symptoms of male urethral cancer include discharge, pain, difficulty urinating up to its retention, palpable compaction, periurethral abscesses and fistulas, malignant priapism. Symptoms of urethral cancer in women include discharge, the presence of a volumetric formation in the area of the external opening of the urethra, difficulty urinating, pain in the urethra and perineum, urinary incontinence, urethrovaginal fistula (bleeding from the vagina).
In one third of patients, enlarged lymph nodes are detected during palpation of the inguinal areas. Tumor thrombosis of the lymphatic vessels of the pelvis and inguinal area can lead to the appearance of edema of the lower half of the body.
The appearance of metastases in parenchymal organs causes the development of corresponding symptoms.
Forms
TNM classification of urethral cancer (cancer of the urethra).
Primary tumor (men and women)
- Tx - the primary tumor cannot be assessed.
- T0 - no signs of primary tumor.
- Ta is a noninvasive papillary, polypoid, or warty (warty) carcinoma.
- Tis - carcinoma in situ (preinvasive).
- T1 tumor extends into subepithelial connective tissue.
- T2 - the tumor extends into the corpus spongiosum of the penis or prostate, or into the periurethral muscle.
- T3 - the tumor extends into the corpus cavernosum or beyond the prostate capsule, or into the anterior vaginal wall, or into the bladder neck.
- T4 - the tumor spreads to other neighboring organs.
Regional lymph nodes
- Nx - regional lymph nodes cannot be assessed.
- N0 - there are no metastases in regional lymph nodes.
- N1 - metastasis in one lymph node no more than 2 cm in greatest dimension.
- N2 - metastasis in one lymph node more than two in greatest dimension or multiple metastases in lymph nodes.
Distant metastases
- Mx - distant metastases cannot be assessed.
- M0 - no distant metastases.
- Ml - distant metastases.
Pathological classification pTNM
Categories pT, pN, pM correspond to categories T, N, M, G - histopathological gradation.
- Gx - the degree of differentiation cannot be assessed.
- G1 - highly differentiated tumor.
- G2 - moderately differentiated tumor.
- G3-4 - poorly differentiated/undifferentiated tumor.
Diagnostics urethral cancer (cancer of the urethra).
A thorough examination, palpation of the external genitalia, perineum and bimanual palpation are necessary to assess the local prevalence of the tumor. The main diagnostic method is urethrocystoscopy, which allows determining the location, size, color, nature of the tumor surface, and the condition of the surrounding mucosa. Urethral cancer (urethra cancer) is characterized by the presence of a solid tumor on a broad base, with an easily bleeding and often ulcerated surface. With significant narrowing of the urethra by a tumor, the presence of a filling defect in the urethra on ascending and micturition urethrograms allows indirectly judging the localization, shape and size of the neoplasm. The degree of local prevalence of the tumor process and the condition of regional lymph nodes are assessed using transabdominal and transvaginal ultrasound, CT and MRI. In order to identify distant metastases, all patients undergo chest X-rays, ultrasound and CT scans of the abdominal organs, retroperitoneal space and pelvis.
Bone scanning is performed only for patients who present the corresponding complaints. Morphological confirmation of the diagnosis is obtained by histological examination of the tumor biopsy. Cytological examination of smears-prints, scrapings from the neoplasm, discharge from the urethra is possible.
What do need to examine?
What tests are needed?
Differential diagnosis
Errors in urethral cancer diagnostics occur in 10% of cases. In men, differential diagnosis of urethral cancer should be carried out with benign tumors, stricture, chronic urethritis, tuberculosis, prostate cancer, and stones. In women, urethral cancer should be distinguished from tumors of the vulva and vagina, benign neoplasms and inflammatory diseases of the urethra, paraurethral cysts, as well as prolapse of the mucous membrane of the urethra, combined with pubescence of the vaginal walls. The only reliable criterion that allows excluding urethral cancer (cancer of the urethra) is morphological verification of the diagnosis.
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Treatment urethral cancer (cancer of the urethra).
Treatment of urethral cancer depends on the stage and location of the tumor. Due to the small number of observations, a standard method for managing patients with this disease has not been developed.
Below are the most commonly accepted approaches.
Treatment of urethral cancer in women
In case of small superficial tumors of the distal urethra T0/Tis, Ta, it is possible to perform TUR or open resection, fulguration, destruction with a neodymium Nd:YAG or carbon CO2 laser. Detection of large superficial (Ta-T1) and invasive (T2) neoplasms serves as an indication for interstitial or combined (interstitial and external beam) radiation therapy. In case of cancer of the distal female urethra at stage T3, as well as in case of relapses after surgical treatment or irradiation of this area, anterior pelvic exenteration is performed with or without preoperative radiation therapy. Palpable inguinal lymph nodes serve as an indication for their removal with urgent histological examination. In cases of confirmation of their metastatic lesion, ipsilateral lymphadenectomy is performed. Routine lymph node dissection in case of non-enlarged regional lymph nodes is not indicated.
Proximal urethral cancer in women is an indication for neoadjuvant radiotherapy and anterior pelvic exenteration with bilateral pelvic lymphadenectomy. Ipsilateral inguinal lymph node dissection is performed with positive cytological or histological results of a biopsy of enlarged lymph nodes in this location.
Massive neoplasms may also require resection of the symphysis and lower branches of the pubic bones with reconstruction of the perineum with a skin-muscle flap. In case of tumors of the proximal part of the urethra less than 2 cm in the largest dimension, an attempt at organ-preserving radiation, surgical or combined treatment is possible.
Treatment of urethral cancer in men
Superficial cancer of the distal urethra T0/Tis-Tl can be successfully treated by TUR or open resection, fulguration, destruction with a neodymium Nd:YAG or carbon CO2 laser. Invasive tumors of the scaphoid fossa are an indication for amputation of the glans, infiltrative neoplasms (T1-3), located more proximally, for amputation of the penis, retreating 2 cm proximal to the edge of the tumor. Radiation therapy for tumors of the distal male urethra is considered as a forced alternative to surgical treatment in patients who refuse penectomy.
Cancer of the bulbomembranous and prostatic urethra in men is an indication for neoadjuvant radiotherapy followed by cystoprostatectomy with urinary diversion, penectomy, bilateral pelvic lymph node dissection with ispsilateral inguinal lymph node dissection (or without it) in the presence of verified metastases in enlarged inguinal lymph nodes. In locally advanced tumors, the symphysis and lower branches of the pubic bones are removed to increase the radicalism of the intervention.
Disseminated urethral cancer is an indication for chemoradiation therapy. If a pronounced clinical response to therapy is obtained, subsequent radical intervention may be attempted. The chemotherapy regimen is determined by the histogenesis of the tumor.
- For transitional cell carcinoma, the M-VAC regimen is used (methotrexate 30 mg/m2 - days 1, 15, 22; vinblastine 3 mg/m2 - days 2, 15, 22; adriamycin 30 mg/m2 - day 2; and cisplatin 70 mg/m2 - day 2).
- For squamous cell carcinoma - chemotherapy including 5-FU (375 mg/m2 - days 1-3), cisplatin (100 mg/m2 - day 1) and calcium folinate (20 mg/m2 - days 1-3).
- For adenocarcinoma - regimens based on 5-FU (375 mg/mg - days 1-3), cisplatin (100 mg/m2 - day 1).
Combined treatment of urethral cancer (urethra cancer) and chemotherapy prevent cell reparation after sublethal doses of radiation. Surgery is performed 4-6 weeks after completion of neoadjuvant treatment.