Urothelial lesions are abnormal growths or changes in the urothelium, the specialized lining of the urinary tract, which includes the bladder, ureters, renal pelvis, and urethra.
Understanding Urothelial Lesions
The urothelium is a stratified epithelium with cell layers that act as a protective barrier. It prevents urine and pathogens from entering the bloodstream and underlying tissues, while also stretching to accommodate varying urine volumes.
Urothelial lesions are classified based on their cellular characteristics and growth patterns, ranging from non-cancerous to malignant. Urothelial papilloma is a benign growth, typically finger-like. These are uncommon and generally do not progress to cancer, though recurrence is possible.
Urothelial dysplasia refers to abnormal cell changes that are precancerous, with the potential to become malignant. It involves abnormalities in urothelial cells without invasion into the basement membrane. Dysplasia is graded as mild, moderate, or severe; severe dysplasia is often synonymous with carcinoma in situ (CIS).
Urothelial carcinoma is a malignancy of the urothelium and the most common type of bladder cancer. These cancers are categorized by invasiveness and grade. Non-muscle invasive bladder cancer (NMIBC) is confined to the mucosa and submucosa, not penetrating the underlying muscle layer. NMIBC includes non-invasive papillary urothelial carcinoma and carcinoma in situ (CIS, a flat, high-grade cancer).
Low-grade tumors are slow-growing and less likely to become invasive, while high-grade tumors and CIS have greater potential for progression. Muscle-invasive bladder cancer (MIBC) has grown into the deeper muscle layer and carries a higher risk of spreading.
Recognizing Symptoms and Diagnosis
Urothelial lesions can manifest with various symptoms. The most common is hematuria, or blood in the urine, which can be visible (gross) or microscopic. Other urinary symptoms include increased frequency, urgency, and painful urination (dysuria). Obstructive symptoms like a reduced urine stream or incomplete voiding may occur if the tumor is near the bladder neck.
Diagnosing urothelial lesions involves a combination of tests. Urinalysis checks for blood or other abnormalities, and urine cytology examines a sample for abnormal cells. While urine cytology has sensitivity for high-grade tumors, a negative result does not rule out malignancy.
Cystoscopy is a primary diagnostic procedure, where a thin, flexible tube with a camera is inserted through the urethra to visually inspect the bladder and urethra for growths. If suspicious areas are found, a biopsy removes tissue for microscopic examination. This tissue analysis definitively diagnoses the lesion’s type, grade, and invasiveness. Imaging tests, such as CT urograms or MRIs, visualize the entire urinary tract and assess for spread. CT urography is an imaging modality for upper tract urothelial carcinoma diagnosis and staging.
Treatment Approaches
Treatment for urothelial lesions depends on the lesion’s type, grade, stage, and location. For non-muscle invasive bladder cancer (NMIBC), the primary treatment is transurethral resection of bladder tumor (TURBT). This surgical procedure removes the tumor through the urethra, serving both diagnostic and therapeutic purposes.
Following TURBT, intravesical therapies may be administered directly into the bladder to reduce recurrence risk. These include chemotherapy agents (e.g., mitomycin C, epirubicin) and immunotherapy with Bacillus Calmette-Guérin (BCG). BCG stimulates an immune response against cancer cells and is a treatment for intermediate and high-risk NMIBC.
When lesions are muscle-invasive (MIBC), more extensive treatments are necessary. Radical cystectomy, the surgical removal of the entire bladder, is a treatment for MIBC, especially without widespread metastasis. In men, this may involve removing the prostate and seminal vesicles; in women, the uterus, fallopian tubes, and part of the vagina may be removed. If the lesion is in the upper urinary tract, a nephroureterectomy (removal of the affected kidney and ureter) may be performed.
For advanced or metastatic urothelial carcinoma, systemic therapies target cancer cells throughout the body. These include chemotherapy (often platinum-based combinations like gemcitabine and cisplatin) and immunotherapy (e.g., pembrolizumab, nivolumab), which helps the body’s immune system fight cancer. Targeted therapies, focusing on specific molecular pathways, are also options for advanced disease.
Long-Term Management and Follow-Up
Long-term management and follow-up are important for individuals with urothelial lesions due to recurrence risk. Even after successful initial treatment, the cancer may return. Regular surveillance is standard to detect new or recurring lesions early.
Follow-up involves periodic cystoscopies to examine the bladder, urine cytology tests for abnormal cells, and imaging studies of the upper urinary tract. The frequency and type of these procedures are tailored to the individual’s risk factors and initial lesion characteristics. For low- and intermediate-risk non-muscle invasive bladder cancers, bladder recurrence rates are around 36.6% within the first five years.
Lifestyle factors also play a role in long-term management and recurrence risk. Smoking cessation is encouraged, as current and former smokers have an increased risk of bladder cancer recurrence and progression. Quitting smoking can lower recurrence risk. Adhering to the follow-up schedule and maintaining a healthy lifestyle contribute to better long-term outcomes.