A three-year Phase III study has been initiated by the US National Cancer Institute’s Early Detection Research Network (EDRN) to validate a test to detect recurrence of bladder cancer through analysis of DNA in cells shed in urine.

"This is the first study of its kind," said Sudhir Srivastava, PhD, who
heads the EDRN as chief of the Cancer Biomarkers Research Group in the Division of Cancer Prevention. "It's the first study testing a marker for bladder cancer, and the first Phase III study for an EDRN-created test."

Bladder cancer, with over 60,000 estimated new cases in the US this year, is both one of the more common cancers and one that has a high recurrence rate. Frequent surveillance of bladder cancer patients is critical, but current procedures have shortcomings. Urine cytology, which checks the number and appearance of cells in urine samples, often fails to detect early tumors. Cystoscopy can give patients a false- positive result in addition to being invasive and unpleasant.

The bladder cancer test uses a technology known as microsatellite DNA
analysis (MSA). Microsatellites, also known as short tandem repeats, are repeating units of one to six nucleotides (e.g. CACACACA) found throughout human chromosomes. These repeating regions are frequently mutated in tumors, either through deletions or by an extension of the number of repeats. For screening for recurrent bladder cancer, DNA can be easily extracted from cells that are normally present in urine and compared with DNA sequences of unaffected cells, such as lymphocytes, from the same patient. Early studies have shown that this non-invasive analysis can have over 90 percent accuracy.

In the validation study, overseen by Jacob Kagan, PhD, 15 different biomarkers in 300 patients diagnosed with bladder cancer will be examined in an effort to predict cancer recurrence. Individuals with healthy bladders and individuals with non-cancerous bladder problems that could be misdiagnosed as cancer, such as kidney stones or urinary tract infections, will be used as controls. The participating institutions will collect samples from patients in this study, and the samples will be analyzed by an independent laboratory.

"The primary goal of this study is to monitor microsatellite analysis for bladder cancer recurrence," said Srivastava, "but the longer goal is to also use the test for early detection of new bladder cancer occurrence."

Final results are expected in September 2007. After Phase III validation, the company that holds the license for the test plans to seek Food and Drug Administration approval to make the test publicly available. In addition, Network researchers are investigating two other early detection tests involving examination of protein biomarkers in blood serum to detect early tumors of the prostate and liver.

For more information about the Early Detection Research Network (EDRN),
visit the EDRN home page at http://www3.cancer.gov/prevention/cbrg/edrn