The urethra is a narrow, muscular tube that serves as the final passageway for urine to exit the body from the bladder. In males, the urethra is significantly longer and also acts as the conduit for semen during ejaculation. Urethral cancer is an exceptionally rare malignancy, accounting for less than one percent of all cancers of the urinary and reproductive systems. This rarity makes the disease challenging to study and understand fully, as most information comes from small patient studies.
Physical Manifestations and Tumor Types
Observable Symptoms
The most common sign prompting medical evaluation is hematuria, which is the presence of blood in the urine or a bloody discharge from the urethra. This bleeding may be visible or microscopic, and it often occurs without pain in the early stages. Another frequent symptom is dysuria, or pain during urination, which can sometimes be mistaken for a urinary tract infection.
As the tumor grows, it can physically obstruct the passageway, leading to a weakening or interruption of the urine stream. Patients may also notice a palpable mass, lump, or thickening along the urethra or in the perineum, the area between the genitals and the anus. In more advanced cases, the cancer may cause enlarged lymph nodes in the groin or pelvic pain, signifying regional spread.
Cellular Classification
Urethral cancers are categorized based on the cell type where the tumor originates, with location influencing the specific type. Transitional cell carcinoma, also known as urothelial carcinoma, is the most common type overall and typically develops in the upper urethra near the bladder. This is the same cell type that lines the bladder, and it is often seen in patients with a history of bladder cancer.
Squamous cell carcinoma is the second most frequent type and tends to form in the squamous cells lining the lower, or distal, segment of the urethra near the external opening. Adenocarcinoma is a less common form that arises in the mucous-secreting glands within the urethral wall, or in urethral diverticula. The specific cell type and location guide both the diagnostic workup and the selection of the treatment strategy.
Key Risk Factors
While the precise cause of urethral cancer remains unknown, several factors are associated with an increased likelihood of developing the disease. A history of chronic inflammation or irritation in the urethra is a significant contributor, often resulting from conditions like urethral strictures or repeated urinary tract infections. Men are three times more likely to develop urethral cancer than women, and incidence rises after the age of 75.
Infections with the human papillomavirus (HPV), a sexually transmitted infection, are recognized as a risk factor, particularly for squamous cell carcinoma. Exposure to previous pelvic radiation therapy for other cancers can also increase risk by damaging healthy cells in the urethra. A personal history of bladder cancer is a strong predictor, as the same urothelial cells line both the bladder and the proximal urethra.
Confirming the Diagnosis
The definitive identification of urethral cancer requires a combination of clinical assessment and specific procedural tests. The process begins with a thorough physical and pelvic examination to check for masses, lumps, or enlarged lymph nodes in the groin. A flexible or rigid cystoscopy is then performed, which involves inserting a thin, lighted tube into the urethra to visually inspect the lining of the urethra and bladder for abnormal growths.
Any suspicious tissue seen during the cystoscopy must be sampled through a biopsy, as this microscopic analysis is the only way to confirm malignant cells and determine the specific cancer type. Once the diagnosis is confirmed, imaging studies are used for staging, which determines the tumor’s size, depth, and spread. Computed tomography (CT) scans, magnetic resonance imaging (MRI), and sometimes positron emission tomography (PET) scans assess local invasion and check for metastasis to regional lymph nodes or distant organs. The Tumor, Node, Metastasis (TNM) staging system classifies the disease, with T describing the primary tumor, N describing lymph node involvement, and M indicating distant spread, which is a primary determinant of prognosis.
Overview of Treatment Modalities
Treatment for urethral cancer is individualized and depends on the tumor’s stage, cell type, and location within the urethra. For early-stage or superficial tumors, surgery is often performed through the urethra using a cystoscope, a technique known as transurethral resection or laser surgery. These minimally invasive, organ-sparing procedures aim to remove the tumor while preserving healthy urethral tissue to maintain urinary function.
More invasive tumors, especially those that have grown deep into the urethral wall or surrounding tissues, require extensive surgical intervention. In males, this may involve a partial or radical penectomy (removal of part or all of the penis), along with a lymph node dissection in the groin. In females, advanced tumors may necessitate an anterior exenteration, which removes the urethra, bladder, and sometimes the front portion of the vagina.
Radiation therapy is a common treatment, used alone for tumors that are not surgically removable or in combination with other modalities. It can be delivered externally (External Beam Radiation Therapy) or internally through brachytherapy, where radioactive sources are placed near the tumor. For locally advanced disease, chemotherapy is often administered before surgery (neoadjuvant therapy) to shrink the tumor and improve the chances of successful surgical removal.
Chemotherapy drugs, often including platinum-based agents, may be used after surgery (adjuvant therapy) to eliminate remaining cancer cells and reduce recurrence risk. For cancer that has spread to distant sites, systemic chemotherapy is the primary approach for disease control. Patients who undergo surgery requiring the removal of the bladder or a significant portion of the urethra will need urinary diversion, such as creating a urostomy, to provide a new pathway for urine exit.