Scientists Begin Validation Study of Test to Detect Recurrence of Bladder Cancer
A three-year study to validate a test to detect the recurrence of bladder cancer has been initiated by the National Cancer Institute (NCI),
part of the National Institutes of Health (NIH), at 13 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." The leading investigator and the coordinator of this study is Dr. Mark Schoenberg, form the James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD..
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.
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For more information about the Early Detection Research Network (EDRN), visit the EDRN home page at http://www3.cancer.gov/prevention/cbrg/edrn
For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer
Information Service at 1-800-4-CANCER (1-800-422-6237).
* The institutions and principal investigators include:
- Johns Hopkins University, James Buchanan Brady Urological Institute, (Mark Schoenberg, M.D.)
- University of Alabama-Birmingham; Birmingham, Ala. (Donald Urban, M.D.)
- Baylor College of Medicine; Houston, Texas (Seth Lerner, M.D.)
- University of Chicago Center for Advanced Medicine; Chicago, Ill. (Gary Steinberg, M.D.)
- Carolina Urologic Research Center; Myrtle Beach, S.C. (Neal Shore, M.D.)
- MD Anderson Cancer Center; Houston, Texas (Colin Dinney, M.D.)
- Memorial Sloan Kettering; New York, N.Y. (Guido Dalbagni, M.D.)
- University of Michigan; Ann Arbor, Mich. (Cheryl Lee, M.D.)
- University of Rochester; Rochester, N.Y. (Edward Messing, M.D.)
- Stanford University; Stanford, Calif. (Joseph Presti Jr., M.D.)
- University of Texas Health Science Center; San Antonio, Texas (Joseph Basler, M.D., Ph.D.)
- University of Toronto; Toronto, Ontario (Laurence Klotz, M.D.)
- Washington University; St. Louis, Mo. (Adam Kibel, M.D.)
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