RESEARCHERS MAKE STRIDES IN URINE TEST FOR BLADDER CANCER.

Byline: Warren E. Leary The New York Times

Scientists said Thursday that they were making significant progress in developing a simple urine test to diagnose bladder cancer, a deadly tumor that can be effectively treated if caught early.

Researchers at the Johns Hopkins University School of Medicine in Baltimore said their experimental test, under development for more than two years, did so well in detecting early bladder cancer in a pilot study with 25 patients that they had started larger-scale human trials.

If the test, which detects abnormal genetic material found in cancer cells, proves valuable in further testing, they said, it could replace or supplement current tests that are effective only half the time in detecting cancer. In addition, they said, the test might be useful in following treated patients to detect if the cancer has recurred.

Dr. David Sidransky, an assistant professor of oncology and urology who was the principle researcher on the study, said results of the tests looked very promising even though they were preliminary and limited because so few patients were in the initial studies.

"We are excited about the results and the prospects of having a reliable, noninvasive and relatively inexpensive diagnostic test for bladder cancer," Sidransky said in an interview. "This is a type of cancer that is highly curable with surgery if it is detected early."

Dr. Barry Kramer of the National Cancer Institute said current bladder cancer tests, which mostly involve looking for cancer cells in tissue samples under a microscope, detected only 20 percent to 30 percent of early cancers. Simpler, more accurate tests that improve this diagnostic ability could lead to earlier treatment and might save lives, he said.

Kramer, director of the early detection and community oncology program at the institute, said: "Tests like the one David Sidransky is working on are promising because they pick up genetic abnormalities, but it remains to be seen if it will result in saving lives. Work like this is extremely important in setting the stage for tests that reveal such a benefit, but this is still a work in progress."

The test developed by the Johns Hopkins researchers, including Dr. Mark P. Schoenberg and Dr. Li Mao, was financed by Oncor Inc., a Gaithersburg, Md., biotechnology company that has an agreement with the university and Sidransky to share sales royalties from products developed from the tests.

In a report appearing Friday in the journal Science, the researchers said bladder cancer was detected with 95 percent accuracy among test subjects in the study. The scientists tested the DNA in 25 urine specimens that were identified only by number, and also tested the samples using the current diagnostic techniques.

Twenty of the specimens came from patients proved by conventional tests to have bladder cancer, and five from control patients who had no evidence of cancer. The genetic tests found the presence of abnormal DNA in the urine of 19 of the 20 cancer patients, and no abnormal DNA in the control patients' urine, the researchers said.

When cancer cells multiply uncontrollably, defects readily occur in areas of the cells' DNA that have no known function, called junk DNA. The researchers use a technique called PCR to multiply this DNA to find more readily the tell-tale defects, known as clonal markers, that indicate cancer.

The test, when first described as promising in 1994, only used these DNA reproduction errors as markers. But Sidransky said that the researchers found that cells from cancer patients also had whole sections of their DNA deleted, and that they could use the absence of these areas as markers, too.

When the researchers tested urine samples against panels of markers representing the DNA errors only, the detection rate of cancer was about 55 percent, Sidransky said. But when DNA deletions were added to the same test panels, detection rates rose to 95 percent.