For Your Patients: Urothelial Cancer 101

— What is it, and who's at risk?

Illustration of a stethoscope with an electrocardiogram in a circle over a bladder with Urothelial Cancer
Key Points

Urothelial cancer is the most common form of bladder cancer, but the term also encompasses cancers of the urethra, ureters, and renal pelvis. Other cancers that start in the bladder are squamous cell carcinoma, adenocarcinoma, small cell carcinoma, and sarcoma, but these represent less than 5% of bladder cancers. The terms urothelial cancer (also called transitional cell cancer) and bladder cancer are often used interchangeably

Who is at risk?

About 83,000 new cases of bladder cancer and 16,700 deaths attributable to bladder cancer are expected in the U.S. in 2023, according to the American Cancer Society. Approximately three to four times as many men as women develop bladder cancer -- mostly in those older than 55. Whites are more likely to be diagnosed with bladder cancer than Blacks or Hispanic Americans.

Smoking and exposure to certain environmental toxins called aromatic amines are the two most common risk factors for the disease. Approximately 30-50% of bladder cancers can be ascribed to smoking, and the longer a person smokes, the greater the risk of bladder cancer. People who have ever received radiation to the pelvis are also at an increased risk of developing bladder cancer.

What are the signs?

The presence of either microscopic or visible ("gross") blood in the urine, called hematuria, is often the first sign of bladder cancer. Microscopic blood in the urine (i.e., that which can be seen only by examination under a microscope) may be a sign of other health problems, such as urinary tract infection, kidney infection, bladder or kidney stones, or an enlarged prostate, but can also be present in some patients with urothelial cancer.

In a patient with bladder cancer, microscopic hematuria usually means the cancer is at an early stage, before it invades the bladder muscle, when about half of bladder cancers are detected. This category of bladder cancer is referred to as non-muscle-invasive bladder cancer. Other signs and symptoms include frequent or painful urination and difficulty with urination (that is, a weak stream). In an advanced stage, lower back pain on one side may also be present.

In contrast, the risk of advanced bladder cancer is much greater with gross hematuria. About one fourth of patients diagnosed with bladder cancer have muscle-invasive bladder cancer -- meaning that the cancer has grown into the muscle wall of the bladder.

How is a patient evaluated if bladder cancer is suspected?

The most common methods to diagnose bladder cancer are cystoscopy and biopsy, urine cytology, and imaging tests, with the first two considered the "gold standard" to diagnose bladder cancer. Fluorescence in situ hybridization (FISH), and tests that look for tumor markers (biomarkers) in the urine may also be evaluated.

Cystoscopy allows the physician to examine the lining of the bladder and the urethra with a thin camera called a cystoscope. Although this is the most sensitive and specific method for identifying bladder cancer, it is an invasive modality accompanied by a risk of complications such as bleeding, infection, and pain. Urinary biomarker tests, while non-invasive, have limited diagnostic value because they are not sensitive enough.

Urine cytology has been the most common initial test performed when a patient has visible blood in the urine. In this instance, a pathologist will analyze the urine sample, looking for cells shed from the bladder lining that appear oddly shaped on examination under the microscope, a feature of malignancy.

If a patient has microscopic blood in the urine, however, urine cytology may have limited value because patients with microscopic blood in their urine rarely have high-grade cancer, and cytology will not reveal a low-grade bladder cancer.

The American Urological Association recently endorsed a personalized strategy for evaluating persons with microscopic hematuria based on certain factors including the patient's age, sex, smoking history, other urothelial cancer risk factors, and the degree and persistence of microhematuria.

Are there additional diagnostic tests beyond cytology?

The evaluation of a person with microscopic blood in the urine may also involve imaging of the upper urinary tract. Imaging is noninvasive and may be sufficient, because the risk of high-grade malignancy is low with microscopic hematuria. The primary imaging technique is a computed tomography (CT) scan of the abdomen and pelvis, called a CT urogram. A CT urogram can usually identify the source of the blood, which could be from the kidney, ureter, bladder or urethra.

CT urography has proven to be accurate in detecting bladder cancer and is useful when a patient presenting with hematuria does not necessarily need further investigation with cystoscopy. For a person who presents with gross hematuria, in addition to urine cytology, a CT urogram is recommended.

In a patient with hematuria, radiology findings on CT urography strongly suggestive of cancer may include presence of a bladder mass, filling defects in the ureter, or in some cases, abnormal lymph nodes near the urinary tract.

If a tumor in the bladder is visible, the next step is transurethral resection of the bladder tumor (TURBT), which is a shaving of the tumor within the bladder. It is performed to confirm the diagnosis and evaluate the extent of the disease and depth of invasion into the bladder wall. TURBT is also a treatment for early-stage (non-muscle-invasive) bladder cancer, and is used to define the depth of invasion of the tumor, which will influence treatment options beyond TURBT.

A tumor identified in the urinary collecting system requires a biopsy for diagnosis. This involves placing a cystoscope through the urethra into the bladder and inserting a guide wire through the cystoscope into the ureter. A ureteroscope inserted over the guide wire allows the doctor to visualize the ureter and kidney, and a biopsy is obtained with a brush placed through the ureteroscope.

Additional workup with a positron emission tomography (also called PET) scan may be performed when the findings on CT scan are indeterminate.

The role of FISH in bladder cancer diagnosis is not clearly defined. The technique fluorescently labels the DNA shed into the urine for abnormalities in specific chromosomes involved in bladder cancer, and is used more to monitor a cancer for a recurrence than it is for diagnosis.

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.