IVD Technology Magazine | IVDT Article Index
Originally published July 1996
Bladder cancer diagnostic screening in need of more-precise test
Conventional medical wisdom holds that finding cancer early is the next best thing to a cure. But the U.S. government has decreed that when it comes to bladder cancer, this doesn't apply. The Guide to Clinical Preventive Service, 2nd Edition issued in 1995 by the U.S. Preventive Services Task Force specifically recommends against routine testing for early detection of bladder cancer. The guidelines are available from the US Government Printing office.
Where does that leave two new bladder-cancer diagnostic tests? It keeps them confined to checks for recurrence of disease, a realm only a fraction as effective as more widespread screening.
As the 10-member task force was formulating its new guide, two diagnostics were getting ready to hit the market: the Bard BTA bladder test (Bard Diagnostic Sciences, Redmond, WA), currently available and Matritech's nuclear-matrix protein test (Matritech, Inc., Newton, MA).
But physicians on the task force found little evidence to support urine testing as a routine screen. The reason: like the prostate-specific antigen test, the most reliable marker for prostate cancer, bladder-cancer diagnostic screening doesn't have a strong track record of documented benefit. To be included in the recommendations, such tests need proof of improved morbidity and mortality.
Bard launched its product this spring after the final go-ahead from FDA. The dipstick like test is the "world's first three-minute bladder-cancer test" and the assay "requires no special training to carry out and interpret," according to company descriptions. The test relies on detection of proteins associated with developing cancer; a yellow color-change indicates positive green indicates negative.
Matritech, with approval pending, also has a urine test, also based on a protein marker. It includes antibodies that recognize nuclear-matrix proteins (NMPs). The advantage, say scientists who have worked with the assay, is that NMPs are specific to cancer cells -- they don't seem to appear without the presence of the carcinoma. Scientific literature shows that bladder cancer has increased by about a third over the past decade. The reasons probably are multifactorial, explains Donald Lamm, MD, professor and chair of urology at the Robert C. Byrd Health Sciences Center of West Virginia University in Morgantown.
One reason for the increase is the influence of environmental factors, such as smoking and exposure to chemicals, particularly in industries as varied as truck driving and hair dressing. But another reason is that more than a quarter of patients with bladder cancer -- which generally shows up first as blood in urine -- may yield a negative cytologic result during cytoscopy, the traditional confirmatory measure.
Clearly a better screening tool is needed, Lamm says. Although neither the Matritech nor Bard test is to be used for initial detection, that is precisely what is needed to find cancer early, when intervention is most likely to pay off, he adds.
Lamm and his colleagues are advocating a selective screening process, in which those at risk are carefully followed. A family history of disease, exposure to workplace chemicals, and smoking all fit into that category, Lamm says.
But, to treat this population, "we really need a precise way of detecting the cancer," he stresses.
An even newer, experimental immunoassay, Aura-Tek FDP by Perimmune, Inc. (Rockville, MD), is showing heightened sensitivity in detecting the cancer, when compared to both hemoglobin-based dipsticks and cytologic evaluations, Lamm says. At the University of Southern California School of Medicine, David Esrig, MD, Richard Cote, MD, and Peter Jones, PhD -- along with others -- have developed a histochemical stain that shows promise in predicting a recurrence, which could also aid in narrowing the patient population in need of close monitoring.
A mutation in the p53 gene, which leads to an increase in a related protein, occurs in significantly more patients who experience a recurrence. "These people are twice as likely to recur," Jones, who is director of the university's Norris Comprehensive Cancer Center.
In the future, genetic testing may be used to further divide that pool of higher-risk people, predicts Lance Willsey, MD, a urologist at Massachusetts General Hospital in Boston. Then one of these more-sensitive assays may be applied to actual screening.
This kind of "second-layer selection" is likely to be the first wave of a true clinical application of gene testing, a fit that may go hand-in-glove with in vitro diagnostics down the road. --Anne Scheck
