Test Package Insert - Part 1
A Rapid Test For the Qualitative Detection of Bladder Tumor
Antigen in Human Urine
U.S.A. Federal law restricts this device to sale and distribution by or on
the order of a physician, or to a clinical laboratory, and use is
restricted to, by or on the order of a physician.
CONTENTS OF THIS SITE IS FOR INFORMATION ONLY. When performing assay
please refer to the most current package insert which accompanies
BTA stat test is an in vitro immunoassay intended for the
qualitative detection of bladder tumor associated antigen in urine of
persons diagnosed with bladder cancer. This test is indicated for use as
an aid in the management of bladder cancer patients in conjunction with
AND EXPLANATION OF THE TEST
Bladder cancer is the fourth most common form of cancer in men and ninth
most common form in women in the United States.1
Approximately 75 to 85% of these patients present with transitional cell
carcinoma (TCC) confined to the superficial mucosa of the bladder.2
The risk of recurrence in these patients is 75%. Patients with previous
diagnosis of bladder cancer have been routinely followed for recurrence
by urine cytology and cystoscopy. Both methods have their limitations.
Cystoscopy is considered the diagnostic standard for sensitivity
and specificity when a biopsy is not obtained. This method is an
invasive procedure associated with patient discomfort, is expensive and
is limited to diagnosis of those tumors that can be visualized.3
Voided urine cytology (VUC), or the examination of urinary
sediment for cancer cells, has several characteristics that contribute
to suboptimal results. Urothelial cells require about a year to
replicate, so few are available for examination in any particular
Exfoliated cells enter a hostile environment of high acidity and low
osmolality which may obscure essential diagnostic features. Standards
for specimen collection, preservation, processing and interpretation
have not been widely accepted. Routine cytology, as a monitoring tool
exhibits variable sensitivity depending on the tumor stage and grade
with lowest sensitivity reported for early stage disease.4,5
In addition, the best quality results are obtained from examination of
samples collected under specific voiding procedures.4
The management of patients with bladder cancer could be improved with a
rapid, simple, urine test that could be performed at point of care or in
the laboratory. Recent studies have shown that the BTA stat test,
which qualitatively detects bladder tumor associated antigen can be
extremely useful in this regard.6,7
The BTA stat test is a single-step, antibody based test which is
performed in only 5 minutes with no pretreatment of the urine
Bladder Tumor Associated Antigen
The monoclonal antibodies used in the BTA stat test were
generated against urine components from patients with histologically
confirmed bladder cancer. Bladder tumor associated antigen was
identified as human complement factor H related protein (hCFHrp) similar
in composition, structure and function to human complement factor H (hCFH).8,9
hCFH, which is also recognized by the monoclonal antibodies utilized in
the BTA stat test, is found in human plasma at concentrations of
approximately 480 µg/mL. In cell culture, hCFHrp was shown to be
produced by several human bladder cancer cell lines, but not by normal
epithelial cell lines.8,9
Using in situ hybridization methods in tumor specimens, hCFHrp was shown
to be produced by cancer cells and macrophages but not by normal
hCFH plays a key inhibitory role in the control of the alternative
complement pathway that functions to lyse cells recognized as foreign to
the host. By interaction with complement factor C3b, hCFH serves to
inhibit the formation of a membrane attack complex, thereby preventing
In vitro, bladder tumor associated antigen interrupts the complement
cascade and protects cells from lysis by complement. This inhibitory
effect can be reversed by the use of monoclonal antibodies specific for
Production of bladder tumor associated antigen may confer a selective
growth advantage to cancer cells in vivo by allowing the cells to evade
the host immune system.
OF THE PROCEDURE
BTA stat test is an immunoassay utilizing two different
monoclonal antibodies (MAbs) to specifically detect the presence of
bladder tumor associated antigen in urine. Each MAb specifically binds
to a different epitope on the target antigen (hCFHrp). One MAb serves as
the hCFHrp capture agent. The second MAb is conjugated to colloidal gold
and serves as the reporter molecule if hCFHrp is present in the
Patient urine is added to the sample well of the device and allowed to
react with the colloidal gold-conjugated reporter antibody. If the
antigen is present in the sample, it will interact with the conjugate to
form an immune complex. The reaction mixture flows through the membrane
which contains zones of immobilized antibodies. In the Patient (P) zone,
antigen-conjugate complexes are trapped by the capture antibody, forming
a visible line. In the absence of the antigen in the patient urine, no
visible line will form. The procedural Control (3) zone contains an
immobilized goat anti-mouse IgG-specific antibody which will capture the
conjugated antibody independently of the presence or absence of the
antigen, thereby always producing a line. This procedural control
assures the operator that each device is working properly.
not use beyond the labeled expiration date.
not reuse disposable test devices. Discard after single use.
not use if pouch is damaged or opened.
not touch the membrane located within the windows.
in vitro diagnostic use.
avoid cross-contamination of samples, use a new dropper (provided
with each device) for each patient urine.
urine samples and used devices as if they are potentially
stat Test Device - individually packaged in a sealed foil pouch
with a urine dropper and a desiccant. Each device incorporates a
membrane-immobilized murine anti-hCFHrp capture MAb and a conjugated
murine anti-hCFHrp MAb in a protein matrix containing sodium azide. The
procedural Control zone contains an immobilized goat anti-mouse IgG-specific
antibody in a protein matrix containing sodium azide.
the BTA stat test kit at 2 - 30°C. Do not freeze. The test kit
is stable when stored at these temperatures until the expiration date
printed on the box label. NOTE: For simplicity and to prevent the
storage of medical devices in home refrigerators, the Instructions for
Home Use recommend room temperature storage only.
OF DEVICE DETERIORATION
a BTA stat test device fails to produce a line in the procedural
Control (3) window when used according to the Patient Test Procedure,
the test is invalid and must be repeated with a new device.
COLLECTION, STORAGE AND PRESERVATION
urine or urine from a catheterized patient is required for the BTA stat
test. Bladder barbotage specimens, serum, plasma or whole blood should
not be used. Urine should be collected without preservatives or
fixatives in a clean urine cup and labeled appropriately. If urine is to
be used for other tests, remove an aliquot of the specimen (a minimum of
2 ml) for this test to avoid contamination. Swirl the urine before
testing. Urine samples may be stored at room temperature for up to 48
hours after collection. If the urine sample is not tested within 48
hours, it should be refrigerated at 2 - 8°C for up to 7 days. If the
refrigerated urine sample is not tested within 7 days, it should be
stored at or below -20°C until tested. A frozen sample is stable for 24
weeks at -20°C including up to 4 freeze/thaw cycles. NOTE: For
simplicity and to prevent the storage of urine samples in home
refrigerators, the Instructions for Home Use recommend room temperature
storage only. If test is provided to patient for home use, supply
patient with a plastic urine collection cup.
not use paper or foam cups for urine specimen collection or storage.
effect of radiation therapy or systemic chemotherapy on the BTA stat
test is unknown.
effect of treatment with intravesical agents, such as BCG, mitomycin
C, Thiotepa, bropiramine (investigational) or interferon
(investigational), is unknown.
antigen concentration variation in first morning urine specimens has
not been determined.
effects of experimental drugs on the BTA stat test are
patients with benign renal disease (such as stones and nephritis),
urinary tract infections, cystitis, sexually transmitted diseases or
renal cancer including upper tract TCC may yield positive results
with the BTA stat test.
trauma to the bladder or urinary tract due to surgery, biopsy, etc.,
the physician should allow ample time for trauma recovery before
using the test.
REQUIRED BUT NOT PROVIDED
collection container (do not use paper or foam cups)
and Negative External Controls, e.g. BTA stat Test Control
Kit (Cat. No. 661105)
HERE FOR PART 2 OF PACKAGE INSERT