3 year study to validate bladder cancer test

Oct 4 2004

A three-year study to validate a test to detect the recurrence of bladder cancer has been initiated by the National Cancer Institute (NCI), at 12 centers across the United States and Canada.

This test was conceived and is being conducted by NCI's Early Detection Research Network (EDRN). By examining genetic changes in DNA obtained through urine samples, the test, if successfully validated, will provide a sensitive and non-invasive method of screening for bladder cancer recurrence.

"This is the first study of its' kind," said Sudhir Srivastava, Ph.D., who heads EDRN as chief of the Cancer Biomarkers Research Group in NCI's 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 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 -- examining the urethra and bladder with a thin lighted scope -- can give patients a false-positive result in addition to being invasive and unpleasant.

The new EDRN-created test looks to improve upon these weaknesses. EDRN, established by NCI in early 2000, is a broad, interdisciplinary consortium whose work is aimed at both identifying and validating cancer biomarkers for use in early cancer detection. Numerous proteins and genes have been linked with a variety of cancers, which can make them targets for therapy, as well as targets for identifying the risk of cancer onset, progression, or recurrence. The validation -- proving that the link accurately signifies the risk for or presence of cancer -- is the critical step to create a truly useful test.

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 to DNA sequences of unaffected cells, such as lymphocytes, from the same patients. Early studies have shown this non-invasive analysis can have over 90 percent accuracy.

In the validation study, overseen by Jacob Kagan, Ph.D., program director of NCI's Cancer Biomarkers Research Group, 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 Commonwealth Biotechnologies Inc., located in Richmond, Va. "The primary goal of this study is to monitor MSA for bladder cancer recurrence," said Srivastava, "but the longer goal is to also use the test for early detection of new bladder cancer occurrence."

This trial will run for three years and final results are expected in September 2007. After Phase III validation, Cangen Biotechnologies Inc., which holds the license for this MSA test, plans to seek Food and Drug Administration approval for this test to make it publicly available. Additionally, EDRN is working on two other early detection tests involving examination of protein biomarkers in blood serum to detect early tumors of the prostate and liver.