A 3-year study to validate a sensitive and noninvasive 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, conceived and conducted by NCI's Early Detection Research Network (EDRN), examines genetic changes in DNA obtained through urine samples. "This is the first study of its kind," says Dr. Sudhir Srivastava, 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." 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 makes them potential targets for identifying the risk of cancer onset, progression, or recurrence. The validation - proving that this link accurately signifies a risk for or presence of cancer - is the critical step in creating a truly useful test.

Bladder cancer is fairly common in the United States (around 60,000 new cases estimated for 2004) and 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.

EDRN's 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 found throughout human chromosomes. These repeating regions are frequently mutated in tumors, either through deletions or by an extension of the number of repeats. To screen 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 from the same patients. Early studies have shown this noninvasive analysis to be accurate more than 90 percent of the time.

In the validation study, overseen by Dr. Jacob Kagan, program director in 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 those with noncancerous 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.

Final results of this study 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 to make the test available commercially. "While the primary goal of this study is to monitor MSA for bladder cancer recurrence," says Dr. Srivastava, "the longer term goal is to use the test for early detection of new bladder cancer occurrence."

EDRN is also working on two other early detection tests involving examination of protein biomarkers in blood serum to detect early tumors of the prostate and liver.