| disease | Female Urethral Cancer |
Primary urethral tumors are relatively rare in clinical practice, with a higher incidence in women than in men. Malignant tumors include carcinoma, fleshy tumor, melanoma, and others. Early symptoms may include urethral bleeding, frequent urination, urgency, and dysuria. As the tumor grows, it can also cause difficulty in urination. Treatment is challenging, and the prognosis is generally poor.
bubble_chart Pathological Changes
The distal two-thirds of the female urethra is lined by squamous epithelium, while the proximal one-third is covered by transitional epithelium. Occasionally, the entire urethra may be lined by squamous epithelium. Periurethral glands are commonly found near the external urethral orifice, occasionally in the mid-urethra, and rarely near the internal urethral orifice. {|###|}Urethral cancer originates from different tissues, leading to varying pathological types. In a domestic study of 73 cases from 11 groups, the pathological types were as follows: 34 cases of squamous cell carcinoma, 28 cases of adenocarcinoma, 4 cases of transitional cell carcinoma, 4 cases of mixed squamous and adenocarcinoma, 2 cases of undifferentiated carcinoma, and 1 case of malignant melanoma. Clinically, urethral cancer is generally divided into distal and proximal types: distal urethral cancer occurs in the distal third of the urethra and may progress to involve the entire urethra. Tumors located in the mid or proximal urethra often involve other parts of the urethra, especially when large and adjacent structures are affected, warranting consideration as pan-urethral cancer. Urethral cancer may also arise within a urethral diverticulum.
The malignancy of urethral cancer is typically classified into three grades, with grade III being the most aggressive. Distal urethral cancer usually has a lower grade, while pan-urethral cancer tends to be higher.The etiology of urethral cancer remains unclear. Urethral caruncle is unlikely to be a precursor, but early-stage urethral cancer can closely resemble a caruncle, polyp, or papilloma, necessitating differential diagnosis. Urethral leukoplakia may be a precancerous lesion.
Urethral cancer often spreads via direct extension, with proximal invasion involving the bladder neck and distal invasion affecting the vestibule, labia, and vagina, potentially leading to urethrovaginal fistula. Pan-urethral cancer tends to infiltrate deep tissues more rapidly. Advanced urethral cancer may be indistinguishable from vulvar cancer in appearance. Lymphatic metastasis is the primary route of spread: distal urethral cancer metastasizes to the inguinal lymph nodes, with some lymphatic vessels ascending above the pubic symphysis, passing between the pyramidalis muscles to reach the pelvic external iliac lymph nodes. Proximal urethral cancer spreads to the obturator and internal/external iliac lymph nodes. At initial diagnosis, 20–57% of patients present with enlarged inguinal lymph nodes, of which 20–80% are due to metastatic cancer. The lymphatic metastasis rate of pan-urethral cancer is higher than that of distal urethral cancer. Most cases with distant metastases already exhibit regional lymph node involvement. Common distant metastatic sites include the lungs, liver, bones, and brain.
bubble_chart Clinical Manifestations
Female urethral cancer is most common in elderly women, with three-quarters of cases occurring in those over 50 years old. Common symptoms include urethral bleeding and hematuria, along with other symptoms such as frequent urination, painful urination, burning sensation during urination, difficulty urinating, pain, itching, or discomfort during intercourse. A mass may be visible or palpable locally. If the tumor undergoes necrosis, ulceration, or infection, yellow or bloody foul-smelling discharge may be observed from the urethra or vagina. Advanced-stage symptoms include weight loss, pelvic pain, perineal abscess, urinary incontinence, urethrovaginal fistula, or urinary retention. A small number of patients may be entirely asymptomatic, with the tumor discovered incidentally during a physical examination for other reasons.
Tumors located in the distal urethra may initially present as a papillary mass or superficial small ulcer, gradually progressing to a cauliflower-like mass protruding from the urethral orifice. The tumor's hardness varies, and its surface may show ulceration and bleeding. Tumors in the proximal urethra may cause local swelling, induration, and tenderness. Vaginal palpation can help estimate the extent of the lesion. Tumors in the proximal urethra sometimes manifest as diffuse infiltration, and a pathological biopsy is necessary for definitive diagnosis.It is generally believed that female urethral cancer originates from the periurethral glands. Immunohistochemical staining shows positive PSA expression. Serum PSA levels in patients are elevated and rapidly decline after surgical tumor removal. Therefore, monitoring serum PSA levels before and after surgery aids in diagnosis and assessing treatment efficacy.
Staging of female urethral cancer: - **Stage O**: Carcinoma in situ. - **Stage A**: Invasion of the submucosal layer. - **Stage B**: Invasion of periurethral muscles. - **Stage C**: Periurethral involvement (C1 vaginal muscle layer, C2 vaginal muscle and mucosa, C3 adjacent structures such as the bladder, labia, or clitoris). - **Stage D**: Metastasis (D1 inguinal lymph nodes, D2 pelvic lymph nodes below the aortic bifurcation, D3 lymph nodes above the aortic bifurcation, D4 distant metastasis).
bubble_chart Treatment Measures
Early treatment is an important measure to improve therapeutic efficacy. The following treatment plan can be referenced:
1. Distal urethral cancer
⑴ Low-stage (O, A, B) tumors: Radiotherapy with radium needles or iridium implants (60Gy) or external radiation (65Gy) is recommended. The efficacy for stages O and A is excellent. Complications of radiotherapy include urethral or meatal stenosis, paraurethral ulcers, urinary incontinence, small intestine inflammation, and intestinal obstruction. Some stage B patients may require surgical treatment due to residual tumors or complications. In the absence of radiotherapy equipment, partial urethrectomy can be performed. For tumors with extensive involvement but no vaginal infiltration, total urethrectomy and bladder flap urethral reconstruction may be considered.
⑵ Stage C and D tumors: Stage C tumors without bladder involvement may undergo bladder-sparing surgery. Stage C tumors involving the bladder and stage D tumors should undergo anterior pelvic exenteration. Preoperative radiotherapy of 40–50Gy should be administered within 4–6 weeks before surgery. Tumors with extensive infiltration should undergo en bloc resection of the entire vagina and vulva. If necessary, the inferior pubic ramus or even the lower half of the pubic symphysis may be resected. For stage D tumors with inguinal lymph node metastasis, inguinal lymphadenectomy should be performed.⑶ For stage O, A, B, and C tumors, close observation of inguinal lymph nodes is recommended; lymphadenectomy should only be performed when metastasis is detected.
⑷ For distal urethral cancer that recurs repeatedly after partial resection or radiotherapy, radical surgery should be performed.
2. Whole-layer urethral cancer: Small lesions in stages O, A, or B may be cured with radiotherapy/local excision, but most cases have already metastasized extensively at diagnosis. Preoperative radiotherapy followed by anterior pelvic exenteration may be considered.
For malignant melanoma, radical surgery is generally advocated. Since many patients die from widespread hematogenous dissemination, the necessity of lymph node dissection remains controversial. For cases with lymph node metastasis, surgical outcomes are poor, and chemotherapy should be administered. Doxorubicin, bleomycin, and dacarbazine (DTIC) have shown some efficacy against certain solid tumors and melanomas and can be used as adjuvant therapy to radiotherapy. For pelvic lymph node metastasis, stirred pulse chemotherapy followed by radiotherapy/surgery may improve therapeutic efficacy.
The prognosis is related to tumor size and location but is more closely associated with tumor stage. Tumors larger than 3 cm and those involving the entire urethra have a poor prognosis. A report from Sun Yat-sen University Cancer Hospital on 15 follow-up cases showed that 9 patients (60%) survived for more than 5 years. Lesions confined to the urethra that can be completely resected have a higher survival rate.
