New bladder cancer tests may aid detection

Less-invasive screening procedures have the potential to increase patient compliance and lower costs.

By Victoria Stagg Elliott, amednews staff. Dec. 25, 2000.

Improved urine tests for bladder cancer are promising to make surveillance for this disease easier and may make screening feasible.

Current posttreatment monitoring includes at least a year of quarterly cystoscopy -- which besides being uncomfortable and expensive, is also associated with a higher risk of urinary tract infections -- and urine cytology. After the first year, frequency is reduced according to physician judgment, but patients must be monitored in some way for the rest of their lives.

"For many patients, particularly those who are being surveyed quite frequently, this is at best a nuisance," said Edward Messing, MD, chair of the urology department at the University of Rochester School of Medicine in New York.

Tests for nuclear matrix proteins (NMP22) and human complement factor H-related protein (BTA stat) in urine have been on the market for the past few years, although they have had limited impact on the use of cystoscopy. In November, Dako Corp., of Carpinteria, Calif., launched its new ImmunoCyt cytopathology test, which uses fluorescence microscopy to look for tumor antigens.

Researchers are also studying other ways of using urinalysis to find the cancer. These include the detection of certain enzymes including telomerase, which is believed to extend the life of a cancer cell; genes that repair mismatched DNA; as well as other molecular markers.

They are all noninvasive tests looking for different signs that point to the same disease. None are expected to eliminate cystoscopy, which would still be needed if the test results were positive. Still, the hope is that newer tests will reduce the frequency with which cystoscopy is done and increase patient compliance with monitoring requirements.

"It appears that NMP22 is a more sensitive test than BTA stat, but they both suffer from insufficient specificity and a false-positive rate that is problematic," said Arthur Sagalowsky, MD, chief of urologic oncology at the University of Texas Southwestern Medical Center in Dallas. "The data on ImmunoCyt are a little newer ... but there's not sufficient experience yet to rank it. It's part of a whole panel of marker studies, some of which are going to turn out to be winners to help us streamline follow-up in the low-risk people and hone in on the high-risk people."

Making screening more feasible

It is also possible that these tests may make screening for bladder cancer more feasible and improve the rate of early detection -- vital because prognosis declines rapidly as time passes and the tumor extends beyond the surface of the bladder.

"Early detection of these tumors has tremendous advantage," said Dr. Messing, speaking at the launch for ImmunoCyt. "They can be scraped out and sometimes medicines can be administered into the bladder to make it less likely to recur."

The disease is the sixth most common malignancy in the United States, resulting in 55,000 cases and 12,000 deaths annually. The relatively low numbers, combined with the lack of an easy test for the disease, has made screening of asymptomatic individuals impractical. It is not recommended by any institution or advocacy organization, although the Food and Drug Administration approved the use of the NMP22 test for screening purposes last January.

Experts say, however, that easier tests, particularly if they are combined with careful selection of patients, may make screening cost-effective. Men older than age 50 who are also smokers or who have had significant exposure to some toxic chemicals are at highest risk and may benefit the most from screening efforts.

Most doctors, though, say screening specifically for the disease is not really the issue. Most bladder cancers are caught when blood in the urine is detected and a cystoscopy is done, but as many as 20% of cases are not diagnosed until they are in the late stages. Specialists said that delays in diagnosis were caused by doctors and patients whose index of suspicion was not high enough and assumed the blood in the urine was from a urinary tract infection, prostate enlargement or kidney stones.

"You have to evaluate those patients to rule out bladder cancer," said Robert Di Loreto, MD, a urologist with the Michigan Institute of Urology in St. Clair Shores, Mich. "All these tests do are adjuncts to a cystoscopic, but they may create a situation where there will be a more cost-effective way to evaluate these people."