Urothelial carcinoma is a type of cancer that begins in the urothelium, which is the specialized lining of the urinary tract. This cancer is most frequently found in the bladder, where it accounts for approximately 90% of all bladder cancer cases in the United States. While it is primarily associated with the bladder, urothelial carcinoma can also develop in the renal pelvis and the ureters, which are the tubes connecting the kidneys to the bladder. The cancer starts when urothelial cells, also called transitional cells because of their ability to stretch and change shape, begin to grow without control.
Defining Urothelial Carcinoma and Its Types
Urothelial carcinoma is often referred to by the older medical term, Transitional Cell Carcinoma (TCC), due to the cell type from which it originates. The urothelium lines the inner surface of the bladder, the ureters, and the renal pelvis. Tumors are classified based on how deeply they have penetrated the bladder wall, which determines the overall prognosis and treatment plan.
The two main classifications are Non-Muscle Invasive Bladder Cancer (NMIBC) and Muscle-Invasive Bladder Cancer (MIBC). NMIBC is the more common form, accounting for about 70% to 80% of new bladder tumors, and it remains confined to the inner lining or the connective tissue just beneath it. Although NMIBC has a better prognosis than the invasive type, it has a high rate of recurrence, and about 20% of cases may progress to the more aggressive form.
MIBC is the more serious classification, as it has grown through the inner layers and into the detrusor muscle wall of the bladder. This deeper invasion significantly increases the likelihood of the cancer spreading to lymph nodes or other organs, leading to a poorer outlook. Muscle-invasive disease accounts for approximately 25% of cases and requires more aggressive treatment approaches than non-invasive tumors.
Factors That Increase Risk
Smoking is the most significant risk factor for developing urothelial carcinoma, with an estimated 50% of bladder cancers resulting from tobacco use. Carcinogens found in tobacco smoke, such as aromatic amines, are filtered by the kidneys and concentrate in the urine, exposing the urothelium to these harmful compounds. Current smokers have an approximately three to four times higher risk of developing this cancer compared to people who have never smoked.
Occupational exposure to certain chemicals is the second most significant risk factor after smoking, accounting for an estimated 20% of all urothelial cancers. Workers in industries dealing with dyes, rubber, paint, and petroleum chemicals are exposed to aromatic amines, which are known human bladder carcinogens. Exposure to arsenic in drinking water, particularly at high concentrations, is also strongly associated with an increased risk of developing the disease.
Another factor is chronic irritation and inflammation of the bladder lining, which can be caused by recurrent urinary tract infections or long-term use of urinary catheters. The incidence of urothelial carcinoma also increases with age, with the majority of patients being diagnosed over the age of 50. Furthermore, men are approximately four times more likely to develop the condition than women.
Recognizing Symptoms and Diagnostic Methods
The most common presenting sign of urothelial carcinoma is hematuria, the presence of blood in the urine, often occurring without pain. This blood may be visible (gross hematuria) or only detectable through a laboratory test (microscopic hematuria). Changes in urination habits are also frequently reported, including a painful or burning sensation during urination, a sudden urge to urinate, or urinating more frequently than usual.
The initial diagnostic workup often begins with a urinalysis to check for blood and abnormal cells in the urine. A procedure called cystoscopy is the primary method for confirming the diagnosis, where a thin, lighted tube with a camera is inserted into the bladder through the urethra. This allows the urologist to visually inspect the lining of the bladder and take tissue samples, or biopsies, for pathological examination.
Imaging techniques are employed to determine the extent of the cancer, a process known as staging. Computerized tomography (CT) scans and magnetic resonance imaging (MRI) can provide detailed images of the urinary tract and surrounding tissues to check for spread to lymph nodes or distant organs.
Treatment Approaches
Treatment for urothelial carcinoma is highly dependent on the stage and grade of the tumor, specifically whether it is non-muscle invasive (NMIBC) or muscle-invasive (MIBC). For NMIBC, the standard initial treatment is a transurethral resection of bladder tumor (TURBT), a surgical procedure to remove the tumor through the urethra. Following TURBT, patients with a higher risk of recurrence receive intravesical therapy, which involves introducing liquid medication directly into the bladder.
Bacillus Calmette-Guérin (BCG) is the most common form of intravesical therapy, which is a weakened bacterium that stimulates an immune response in the bladder lining to destroy cancer cells. For patients with high-risk NMIBC that does not respond to BCG, immune checkpoint inhibitors are now approved as a non-surgical option.
For MIBC, the standard approach involves a radical cystectomy, which is the surgical removal of the entire bladder, often along with nearby lymph nodes. Systemic chemotherapy, typically cisplatin-based, is frequently given before the surgery to shrink the tumor and destroy any microscopic spread, a process known as neoadjuvant therapy. Emerging treatment options include immunotherapy, which utilizes drugs to harness the body’s immune system against advanced urothelial cancer.