Although cytology has long been the gold standard for bladder cancer screening, including monitoring for recurrences, it is far from perfect (see Question 33), and there is great interest in finding an even better test. Currently, at least four other markers are approved by the Food and Drug Administration (FDA), although none of them are clearly better than cytology. In addition to these four, many new tests are being developed. The four listed here are those that are currently available to patients.
NMP 22: NMP 22 (Matritech, Newton, MA) is a protein that undergoes changes when a bladder cell becomes cancerous. A test for this protein has been developed that looks for the altered protein in the urine; 70% to 80% of patients with bladder cancer will have a positive result, but only 64% of patients with a positive result have cancer. A positive result in a patient without cancer is called a false-positive result. The high false-positive result, often caused by simple inflammation in the bladder, limits its utility.
BTA: BTA (Polymedco, Cortlandt Manor, NY ) is another protein found in bladder cancer cells but not in normal cells. Tests to detect BTA in the urine are also available. The test identifies 50% to 80% of patients with bladder cancer, but the false-positive rate is similar to NMP 22, limiting its use.
ImmunoCyt: ImmunoCyt tests for the presence of three different proteins at the same time. Its ability to detect bladder cancer has varied in different studies from 40% to 100%. The false-positive rate is somewhat better than NMP 22 or BTA at approxi-mately 20%. ImmunoCyt appears to be somewhat better in detecting low-grade tumors.
FISH (fluorescent in situ hybridization) (UroVysion kit, Visys, Inc./Abbott Laboratories, Downers Grove, IL): This test is able to look directly at the DNA of a cell, searching for malignant cells. Under the microscope, malignant cells light up like a neon sign. It is able to detect more cases of bladder cancer than conventional cytology (73% for FISH vs. 63% for cytology) with a false-positive rate of close to 0%. It may detect a tumor up to a year before it can be seen with a cystoscope. Even more, it continues to work well in patients after they have had intravesical therapy with BCG or mitomycin C, situations in which cytology and ImmunoCyt do not work well at all.
Both ImmunoCyt and UroVysion use fluorescent dyes, are time consuming, and require trained personnel to perform.
There are a number of investigational tests for bladder cancer being evaluated in clinical studies including: urinary bladder cancer test, BLCA-1, BLCA-4, hyaluronic acid, hyaluronidase, Lewis X antigen, microsatellite analysis, QuantiCYt, soluble Fas, survivin, and telomerase.
These tests are currently best used to decrease the frequency of cystoscopy. None of them are yet able to replace cystoscopy.