Urine tests can foretell bladder cancers.

Workers exposed to certain chemicals face an increased risk of bladder cancer. U.S. and Chinese scientists monitoring workers handling one such compound, benzidine, now report that two unconventional urine tests can often reveal who is developing bladder cancer long before tumors appear.

Bladder cells that are shed into the urine reflect the condition of the bladder's lining. To assess the two screening tests, the researchers periodically obtained urine samples between 1991 and 1997 from 1,788 Chinese men and women who had worked with benzidine dyes in clothing factories during the 1970s. The researchers also obtained urine samples from 373 unexposed workers.

One of the tests analyzed cells in urine for excess DNA, an early sign of aberrant growth. The other detected the glycoprotein p300, which is frequently present in bladder tumors. The scientists also monitored the workers for warning signs of cancer using conventional means, such as blood in the urine and the presence of abnormal bladder cells in microscopic analysis of urine.

The researchers periodically examined by cystoscopy the most-exposed workers. In this procedure, a physician inserts into the bladder through a patient's urethra a thin tube with a tiny lens and a sampling device at the end. This is how growths inside the bladder are typically diagnosed and sometimes removed.

Of 30 participants who developed bladder cancer during the trial, 28 had been exposed to benzidine on the job and two had not. Workers whose cells from urine tested positive for excess DNA and contained p300 were 81 times as likely to develop cancer subsequently as were people without either marker, the researchers report in the March 21 JOURNAL OF THE NATIONAL CANCER INSTITUTE.

A worker with a positive result in either test, but not both, had 20 times the risk of developing bladder cancer that a worker testing negative to both tests had, says study coauthor George P. Hemstreet III of the University of Oklahoma Health Sciences Center in Oklahoma City. Conventional tests finding abnormal cells or blood in urine indicated a 15-fold increase in risk.

These conventional tests can predict bladder cancer but do so with little lead time, says Hemstreet. Blood in the urine preceded a cancer diagnosis by cystoscopy in the workers by only 3 months on average, and unusual cell growth appeared only 8 months before diagnosis.

In contrast, p300 or extra DNA in cells in the urine showed up an average of 15 months before a diagnosis of cancer in heavily exposed workers and 33 months before diagnosis in moderately exposed workers. "This tells us there are fingerprints normally appearing in cells in the urine that are there years before the tumor develops," Hemstreet says.

"This is some of the most important work on biomarkers in premalignant conditions of the bladder that I'm aware of," says Seth P. Lerner of Baylor College of Medicine in Houston. These tests have added value because urine samples are easily obtained, he says.

The markers could prove particularly useful in monitoring former bladder cancer patients, 60 percent of whom can expect a second bout of cancer, says Fredrick S. Leach of the National Cancer Institute in Bethesda, Md.

David Atkins of the U.S. Public Health Service in Rockville, Md., calls the study promising but cautions that it doesn't prove that biomarkers can catch the most dangerous cancers early enough to help much. Some bladder cancers may grow too fast for detection, leaving physicians to catch mainly slow cancers that they might have spotted by other means, anyway, he says.