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 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.
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:
- 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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