0843

E
system Total PSA
7K70
B7K700
77-4138/R2

Total PSA
This package insert must be read carefully prior to use. Package insert instructions must be carefully followed.
Reliability of assay results cannot be guaranteed if there are any deviations from the instructions in this package
insert.

Note Changes Highlighted

Revised June, 2007

Key to symbols used

List number Expiration date

In Vitro Diagnostic Lot number

Medical Device
Reagent Lot
Store at 2-8°C

Sample Cups
Consult instructions for use
Septums
Caution: consult
accompanying documents
Control Number
Serial Number
Reaction
Vessels
Manufacturer Replacement
Caps
See REAGENTS section for a full explanation of symbols
used in reagent component naming.

ABBOTT
Diagnostics Division

1
WARNING: The concentration of total PSA in a given specimen, measurement of serum PSA concentrations offers several advantages
determined with assays from different manufacturers, can vary due in the early detection of prostate cancer. The procedure is more
to differences in assay methods and reagent specificity. The results acceptable to patients, the result is objective and quantitative, and
reported by the laboratory to the physician must include the identity of is independent of the examiners skill. In several recent studies of
the total PSA assay used. Values obtained with different assay methods, healthy men 50 years or older, serum PSA levels had the greatest
including Abbott PSA assays, cannot be used interchangeably. If, in the ability to predict prostate cancer. These studies concluded that not
course of monitoring a patient, the assay method used for determining only is serum PSA measurement a useful addition to rectal examination
total PSA levels serially is changed, additional sequential testing should and ultrasonography in the detection of prostate cancer, but that it
be carried out. Prior to changing assays, the laboratory MUST confirm is also the most accurate of the three tests for this purpose.14,15 In
baseline values for patients being serially monitored. January 1992, the American Urological Association endorsed annual
examination with DRE and PSA, for early detection of prostate cancer,
NAME beginning at age 50.16 This was reaffirmed by the American Cancer
ARCHITECT Total PSA (Prostate Specific Antigen) Society in November 1992.17 The combined use of DRE and PSA
INTENDED USE has been shown to result in an increased detection of early stage
prostate cancer; however, the benefit of early detection on patient
The ARCHITECT Total PSA assay is a Chemiluminescent Microparticle outcome has not been proven and is the subject of ongoing clinical
Immunoassay (CMIA) for the quantitative determination of total PSA trials.4-7,13-15,18,19
(both free PSA and PSA complexed to alpha-1-antichymotrypsin) in PSA testing can have significant value in detecting metastatic or
human serum: persistent disease in patients following surgical or medical treatment
1. As an aid in the detection of prostate cancer when used in of prostate cancer. Persistent elevation of PSA following treatment, or
conjunction with digital rectal exam (DRE) in men 50 years or older. an increase in a post-treatment PSA level is indicative of recurrent or
Prostatic biopsy is required for diagnosis of cancer. residual disease. PSA testing is widely accepted as an adjunctive test
2. As an adjunctive test to aid in the management of prostate cancer in the management of prostate cancer patients.3-7
patients.
BIOLOGICAL PRINCIPLES OF THE PROCEDURE
SUMMARY AND EXPLANATION OF TEST The ARCHITECT Total PSA assay is a two-step immunoassay
Prostate specific antigen (PSA), a member of the human kallikrein to determine the presence of total PSA (both free PSA and PSA
gene family, is a serine protease with chymotrypsin-like activity. The complexed to alpha-1-antichymotrypsin) in human serum, using
mature form of PSA is a single chain glycoprotein of 237 amino acids Chemiluminescent Microparticle Immunoassay (CMIA) technology
containing 7-8% carbohydrate as a single N-linked oligosaccharide with flexible assay protocols, referred to as Chemiflex.
side chain. PSA has a molecular weight of approximately 30,000 In the first step, sample and anti-PSA coated paramagnetic
daltons.1,8,33,34 microparticles are combined. PSA present in the sample binds to the
The major site of PSA production is the glandular epithelium of the anti-PSA coated microparticles. After washing, anti-PSA acridinium-
prostate. PSA has also been found in breast cancers, salivary gland labeled conjugate is added in the second step. Pre-Trigger and
neoplasms, periurethral and anal glands, cells of the male urethra, Trigger Solutions are then added to the reaction mixture; the resulting
breast milk, blood and urine.1,2 PSA produced in the prostate is secreted chemiluminescent reaction is measured as relative light units (RLUs). A
into the seminal fluid in high concentrations. A major function of PSA direct relationship exists between the amount of total PSA in the sample
is the proteolytic cleavage of gel-forming proteins in the seminal fluid, and the RLUs detected by the ARCHITECT i* optical system.
resulting in the liquification of the seminal gel and increased sperm For additional information on system and assay technology, refer to
mobility.1 Low levels of PSA are found in the blood as a result of the ARCHITECT System Operations Manual, Section 3.
leakage of PSA from the prostate gland. Increasing levels of serum * i = immunoassay
PSA are associated with prostatic pathology, including prostatitis, benign
prostatic hyperplasia (BPH), and cancer of the prostate.1,3-7 REAGENTS
PSA occurs in three major forms in blood. The major immunodetectable Reagent Kit, 100 Tests/500 Tests
form is PSA complexed with the serine protease inhibitor, alpha- NOTE: Reagent Kit Configurations vary based on order.
1-antichymotrypsin (PSA-ACT). Uncomplexed, or free PSA, is the
ARCHITECT Total PSA Reagent Kit (7K70)
other immunodetectable form of PSA in serum. The majority of free
PSA in serum appears to be an inactive form that cannot complex • 1 or 4 Bottle(s) (6.6 mL for 100 test bottle/
with protease inhibitors and may be either a PSA zymogen or an 27.0 mL for 500 test bottle) Anti-PSA (mouse, monoclonal) coated
enzymatically-inactive, cleaved form of PSA. Equimolar-response PSA Microparticles in TRIS buffer with protein (bovine) stabilizers.
assays have an equivalent response to both free PSA and PSA-ACT.1 Preservative: Antimicrobial Agents.
The ARCHITECT Total PSA assay is an equimolar assay. A third form • 1 or 4 Bottle(s) (5.9 mL for 100 test bottle/26.3 mL for
of PSA, a complex with alpha-2-macroglobulin, is not detectable with 500 test bottle) Anti-PSA (mouse, monoclonal) acridinium-labeled
current immunoassays for PSA due to the engulfment and subsequent Conjugate in MES buffer with protein (bovine) stabilizers. Minimum
masking of PSA epitopes by the alpha-2-macroglobulin molecule.1,8,9 concentration: 10 ng/mL. Preservative: Antimicrobial Agents.
Prostate cancer is the most frequently diagnosed cancer and the
Assay Diluent
second leading cause of cancer deaths in men in the United States.10
Early diagnosis of carcinoma of the prostate is hindered by the lack ARCHITECT i Multi-Assay Manual Diluent (7D82-50)
of symptoms in men with localized tumors. Therefore, early detection • 1 Bottle (100 mL) ARCHITECT i
requires a simple, safe, and inexpensive test for the disease in Multi-Assay Manual Diluent containing phosphate buffered saline
asymptomatic men. The traditional method for detection of prostate solution. Preservative: Antimicrobial Agent.
cancer is the digital rectal examination (DRE). However, only 30 to 40%
Other Reagents
of cancers detected by DRE screening are expected to be confined
to the prostate. The frequent finding of locally advanced prostate ARCHITECT i Pre-Trigger Solution
cancer in screened patients may be due to the inability of DRE to • Pre-Trigger Solution containing 1.32%
detect tumors of small volume that are most likely to be confined to (w/v) hydrogen peroxide.
the prostate.11 Since patients with small tumors are believed to have
ARCHITECT i Trigger Solution
the best prognosis, it can be concluded that DRE has limited sensitivity
in detecting those tumors with the greatest potential for cure.12 • Trigger Solution containing 0.35N sodium
In a 1990 publication by Cooner et al., data was presented regarding hydroxide.
the clinical use of other diagnostic modalities such as prostate ARCHITECT i Wash Buffer
ultrasonography and serum prostate specific antigen for early NOTE: Bottle and volume varies based on order.
detection of prostate cancer. This study found that there was a • Wash Buffer containing phosphate buffered saline
significant increase in predictability for cancer when the DRE and solution. Preservative: Antimicrobial Agent.
PSA tests were abnormal.13 Several other studies have shown that the

2
WARNINGS AND PRECAUTIONS Indications of Reagent Deterioration
• For In Vitro Diagnostic Use. When a control value is out of the specified range, it may indicate
deterioration of the reagents or errors in technique. Associated test
• CAUTION: This product requires the handling of human results may be invalid and may require retesting. Assay recalibration
specimens. It is recommended that all human sourced materials may be necessary. For troubleshooting information, refer to the
be considered potentially infectious and handled with appropriate ARCHITECT System Operations Manual, Section 10.
biosafety practices. Elevated Sample Results
Safety Precautions Protein build up on the sample pipetter probe may result in individual
samples exhibiting elevated concentration due to carryover from
For product not classified as dangerous per European Directive
a sample with very high PSA concentration. For troubleshooting
1999/45/EC as amended - Safety data sheet available for
information, refer to the ARCHITECT System Operations Manual,
professional user on request.
Section 10.
• For a detailed discussion of safety precautions during system
operation, refer to the ARCHITECT System Operations Manual, INSTRUMENT PROCEDURE
Section 8. • The ARCHITECT Total PSA assay file must be installed on the
Handling Precautions ARCHITECT i System from the ARCHITECT i Assay CD-ROM prior
to performing the assay. For detailed information on assay file
• Do not use reagent kits beyond the expiration date. installation and on viewing and editing assay parameters, refer to
• Do not mix reagents from different reagent kits. the ARCHITECT System Operations Manual, Section 2.
• Prior to loading the ARCHITECT Total PSA Reagent Kit on the • For information on printing assay parameters, refer to the ARCHITECT
system for the first time, the microparticle bottle requires mixing System Operations Manual, Section 5.
to resuspend microparticles that have settled during shipment. For • For a detailed description of system procedures, refer to the
microparticle mixing instructions, refer to the PROCEDURE, Assay ARCHITECT System Operations Manual.
Procedure section of this package insert.
• The default result unit for the ARCHITECT Total PSA assay is ng/mL.
• Septums MUST be used to prevent reagent evaporation and An alternate result unit, μg/L, may be selected for reporting results
contamination, and to ensure reagent integrity. Reliability of assay by editing assay parameter “Result concentration units”, to μg/L.
results cannot be guaranteed if septums are not used according The conversion factor used by the system is 1.0.
to the instructions in this package insert.
• To avoid contamination, wear clean gloves when placing a SPECIMEN COLLECTION AND PREPARATION FOR
septum on an uncapped reagent bottle. ANALYSIS
• Once a septum has been placed on an open reagent bottle, do • Only human serum may be used in the ARCHITECT Total PSA assay.
not invert the bottle as this will result in reagent leakage and may Follow the tube manufacturer’s processing instructions for serum
compromise assay results. collection tubes.
• Over time, residual liquids may dry on the septum surface. These • It is recommended to obtain specimens for PSA testing prior to
are typically dried salts which have no effect on assay efficacy. procedures involving manipulation of the prostate.
• For a detailed discussion of handling precautions during system • Follow these package insert instructions as well as the specimen
operation, refer to the ARCHITECT System Operations Manual, collection tube manufacturer’s instructions for specimen collection
Section 7. and preparation for analysis. Refer to the specimen collection tube
manufacturer’s instructions for centrifugation time and speed.
Storage Instructions
• Insufficient processing of sample, or disruption of the sample during
transportation may cause depressed results.
• The ARCHITECT Total PSA Reagent Kit must be stored • For optimal results, serum specimens should be free of fibrin,
at 2-8°C and may be used immediately after removal from 2-8°C red blood cells, or other particulate matter. Centrifuge specimens
storage. containing fibrin, red blood cells, or particulate matter prior to use
• When stored and handled as directed, reagents are stable until the to ensure consistency in the results.
expiration date. • Ensure that complete clot formation in serum specimens has taken
• The ARCHITECT Total PSA Reagent Kit may be stored on-board place prior to centrifugation. Some specimens, especially those
the ARCHITECT i System for a maximum of 30 days. After 30 days, from patients receiving anticoagulant or thrombolytic therapy may
the reagent kit must be discarded. For information on tracking exhibit increased clotting time. If specimens are centrifuged before a
on-board time, refer to the ARCHITECT System Operations Manual, complete clot forms, the presence of fibrin or particulate matter may
Section 5. cause erroneous results. Centrifuge specimens containing fibrin,
• Reagents may be stored on or off the ARCHITECT i System. If red blood cells, or particulate matter. Note that interfering levels
reagents are removed from the system, store them at 2-8°C (with of fibrin may be present in samples that do not have obvious or
septums and replacement caps) in an upright position. For reagents visible particulate matter.
stored off the system, it is recommended that they be stored in • If proper specimen collection and preparation cannot be verified,
their original trays and boxes to ensure they remain upright. If the or if samples have been disrupted due to transportation or sample
microparticle bottle does not remain upright (with a septum handling, an additional centrifugation step is recommended.
installed) while in refrigerated storage off the system, the reagent Centrifugation conditions should be sufficient to remove particulate
kit must be discarded. After reagents are removed from the system, matter. Aliquots poured versus pipetted from specimen tube types
you must initiate a scan to update the on-board stability timer. that do not include serum separators are at higher risk of including
particulates and generating depressed results.
• Failure to follow these instructions may result in depressed
specimen results.

3
• Specimens may be stored for up to 24 hours at 2-8°C prior to being Assay Procedure
tested. If testing will be delayed more than 24 hours, specimens • Before loading the ARCHITECT Total PSA Reagent Kit on the system
should be removed from the clot or serum separator and stored for the first time, the microparticle bottle requires mixing to resuspend
frozen at -20°C or colder.20,21 microparticles that have settled during shipment:
NOTE: Samples which may be tested for free PSA should be • Invert the microparticle bottle 30 times.
removed from the clot within 3 hours. • Visually inspect the bottle to ensure microparticles are
• The ARCHITECT i System does not provide the capability to verify resuspended. If microparticles are still adhered to the bottle,
specimen type. It is the responsibility of the operator to verify continue to invert the bottle until the microparticles have been
the correct specimen type is used in the ARCHITECT Total PSA completely resuspended.
assay. • Once the microparticles have been resuspended, remove and
• Use caution when handling patient specimens to prevent cross discard the cap. Wearing clean gloves, remove a septum from
contamination. Use of disposable pipettes or pipette tips is the bag. Squeeze the septum in half to confirm that the slits are
recommended. open. Carefully snap the septum onto the top of the bottle.
• Do not use grossly hemolyzed specimens. • If the microparticles do not resuspend, DO NOT USE. Contact
• For optimal results, inspect all samples for bubbles. Remove your local Abbott representative.
bubbles with an applicator stick prior to analysis. Use • Order tests.
a new applicator stick for each sample to prevent cross • Load the ARCHITECT Total PSA Reagent Kit on the ARCHITECT i
contamination. System. Verify that all necessary assay reagents are present.
• Multiple freeze-thaw cycles of specimens should be avoided. Ensure that septums are present on all reagent bottles.
Specimens must be mixed THOROUGHLY after thawing, by vortexing. • The minimum sample cup volume is calculated by the system and
Thawed samples containing red blood cells or particulate matter, is printed on the Orderlist report. No more than 10 replicates may
or which are hazy or cloudy in appearance must be centrifuged be sampled from the same sample cup. To minimize the effects of
prior to use to ensure consistency in the results. evaporation, verify adequate sample cup volume is present prior to
• Specimens with obvious microbial contamination should not be running the test.
used. • Priority: 100 μL for the first Total PSA test plus 50 μL for each
• When shipped, specimens must be packaged and labeled in additional Total PSA test from the same sample cup
compliance with applicable state, federal, and international • ≤ 3 hours onboard: 150 μL for the first Total PSA test plus 50 μL
regulations covering the transport of clinical specimens and for each additional Total PSA test from the same sample cup
infectious substances. Specimens that will not be assayed within
• > 3 hours onboard: additional sample volume is required. Refer
24 hours should be stored/shipped frozen. Prior to shipment, it is
to the ARCHITECT System Operations Manual, Section 5 for
recommended that specimens be removed from the clot or serum
information on sample evaporation and volumes.
separator.
• Press RUN. The ARCHITECT i System performs the following
• ARCHITECT Total PSA Calibrators and Controls should be mixed by
function:
gentle inversion prior to use.
• Moves the sample to the aspiration point
PROCEDURE • If using primary or aliquot tubes, use the sample gauge to ensure
Materials Provided sufficient patient specimen is present.
• 7K70 ARCHITECT Total PSA Reagent Kit • To obtain the recommended volume requirements for the
ARCHITECT Total PSA Calibrators and Controls, hold the bottles
Materials Required but not Provided vertically and dispense 7 drops of each calibrator or 4 drops of
• ARCHITECT i System each control into each respective sample cup.
• ARCHITECT i Assay CD-ROM • Load samples
• 7K70-01 ARCHITECT Total PSA Calibrators • For information on loading samples, refer to the ARCHITECT
• 7D82-50 ARCHITECT i System Operations Manual, Section 5.
• ARCHITECT i • Press RUN. The ARCHITECT i System performs the following
• ARCHITECT i functions:
• ARCHITECT i • Moves the sample carrier to the aspiration point
• ARCHITECT i • Loads a reaction vessel (RV) into the process path
• ARCHITECT i • Aspirates and transfers sample into the RV
• ARCHITECT i • Advances the RV one position and transfers microparticles into
the RV
• ARCHITECT i
• Mixes, incubates and washes the reaction mixture
• Pipettes or pipette tips (optional) to deliver the volumes specified
on the patient or control order screen. • Adds conjugate to the RV
• For information on materials required for maintenance procedures, • Mixes, incubates and washes the reaction mixture
refer to the ARCHITECT System Operations Manual, Section 9. • Adds Pre-Trigger and Trigger Solutions
• Measures chemiluminescent emission to determine the quantity
Materials Available but not Provided of total PSA in the sample
• 7K70-10 ARCHITECT Total PSA Controls • Aspirates contents of RV to liquid waste and unloads RV to solid
waste
• Calculates the result
• For information on ordering patient specimens and controls, and
general operating procedures, refer to the ARCHITECT System
Operations Manual, Section 5.
• For optimal performance, it is important to follow the routine
maintenance procedures defined in the ARCHITECT System
Operations Manual, Section 9. If your laboratory requires more
frequent maintenance, follow those procedures.

4
Specimen Dilution Procedures Flags
Specimens with a total PSA value exceeding 100 ng/mL are flagged with • Some results may contain information in the Flags field. For a
the code “>100.000” and may be diluted using either the Automated description of the flags that may appear in this field, refer to the
Dilution Protocol or the Manual Dilution Procedure. ARCHITECT System Operations Manual, Section 5.
• If using the Automated Dilution Protocol, the system performs a
1:10 dilution of the specimen and automatically calculates the LIMITATIONS OF THE PROCEDURE
concentration of the sample before dilution and reports the result. • Specimens from patients who have received preparations of mouse
• Dilutions other than 1:10 should be done manually. monoclonal antibodies for diagnosis or therapy may contain human
• For example, to perform a 1:20 dilution, add 50 μL of the patient anti-mouse antibodies (HAMA). Such specimens may show either
specimen to 950 μL of ARCHITECT i Multi-Assay Manual Diluent falsely elevated or depressed values when tested with assay kits
(7D82-50). which employ mouse monoclonal antibodies.22,23 ARCHITECT Total
PSA reagents contain a component that reduces the effect of HAMA
• The operator must enter the dilution factor in the Patient or
reactive specimens. Additional clinical or diagnostic information
Control order screen. All assays selected for that order will be
may be required to determine patient status.
diluted. The system will use this dilution factor to automatically
calculate the concentration of the sample before dilution and • Heterophilic antibodies in human serum can react with reagent
report the result. The dilution should be performed so that the immunoglobulins, interfering with in vitro immunoassays.24 Patients
diluted result reads greater than 0.4 ng/mL. routinely exposed to animals or animal serum products can be
prone to this interference and anomalous values may be observed.
• For detailed information on ordering dilutions, refer to the
Additional information may be required for diagnosis.
ARCHITECT System Operations Manual, Section 5.
• The concentration of PSA in a given specimen, determined with
Calibration assays from different manufacturers, can vary due to differences
• To perform an ARCHITECT Total PSA calibration, test calibrators 1 in assay methods, calibration, and reagent specificity.1,25,26
and 2 in duplicate. A single sample of all levels of total PSA controls • Quality control samples may be produced by introducing seminal fluid
must be tested to evaluate the assay calibration. Ensure that assay PSA into a human serum matrix. PSA in serum and seminal fluid may
control values are within the concentration ranges specified in the exist in different forms. The concentration of PSA in these controls,
control package insert. Calibrators should be priority loaded. determined with assays from different manufacturers, can vary due
• Calibration range: 0 - 50 ng/mL. to differences in assay methods, calibration, reagent specificity,
• The assay protocol allows for the range to be extended to and the form of PSA that is present; therefore, it is important to
100 ng/mL. use assay-specific values to evaluate control results.
• Once an ARCHITECT Total PSA calibration is accepted and stored, • Hormonal therapy may affect PSA expression; therefore, a low
all subsequent samples may be tested without further calibration PSA level after any treatment that includes hormonal therapy
unless: may not adequately reflect the presence of residual or recurrent
disease.27
• A reagent kit with a new lot number is used.
• In most instances, specimens obtained from patients immediately
• Controls are out of range.
following digital rectal examination show no clinically significant
• For detailed information on how to perform an assay calibration, increases in PSA levels. 28 However, prostatic massage,
refer to the ARCHITECT System Operations Manual, Section 6. ultrasonography, and needle biopsy may cause clinically
QUALITY CONTROL PROCEDURES significant elevations.29 PSA levels may also be increased following
ejaculation.30
The recommended control requirement for the ARCHITECT Total PSA
assay is a single sample of all control levels tested once every 24 hours • Active free PSA in the serum at the time of blood sampling can
each day of use. If the quality control procedures in your laboratory continue to complex with serum protease inhibitors, especially
require more frequent use of controls to verify test results, follow your alpha-2-macroglobulin, resulting in a rapid decrease in PSA levels
laboratory-specific procedures. Ensure that assay control values are of the active form of free PSA.31
within the concentration ranges specified in the package insert. • Serum PSA concentrations should not be interpreted as absolute
evidence for the presence or absence of prostate cancer. Elevated
Verification of Assay Claims concentrations of PSA may be observed in the serum of patients
For protocols to verify package insert claims, refer to the ARCHITECT with benign prostatic hyperplasia or other nonmalignant disorders
System Operations Manual, Appendix B. The ARCHITECT Total PSA as well as in prostate cancer. Furthermore, low PSA concentrations
assay belongs to method group 1. are not always indicative of the absence of cancer. The PSA value
should be used in conjunction with information available from
RESULTS
clinical evaluation and other diagnostic procedures such as DRE.
The ARCHITECT Total PSA assay utilizes a 4 Parameter Logistic Some early cases of prostate cancer will not be detected by PSA
Curve fit data reduction method (4PLC, Y weighted) to generate a testing; the same is true for DRE. Prostatic biopsy is required for
calibration curve. the diagnosis of cancer.
Alternate Result Units
EXPECTED VALUES FOR DETECTION OF PROSTATE
• The default result unit for the ARCHITECT Total PSA assay is ng/mL.
When the alternate result unit, μg/L, is selected, the conversion CANCER
factor used by the system is 1.0. [Values developed for the ARCHITECT i2000 analyzer.]
• Conversion Formula: (Concentration in ng/mL) x (1.0) = μg/L A prospective study was conducted at seven clinical sites to
demonstrate the usefulness of PSA in the detection of prostate
cancer when used in conjunction with DRE. All clinical data presented
supporting the detection claim were generated using the ARCHITECT i
System and ARCHITECT Total PSA assay reagents. A total of 531 men
50 years of age or older participated in the study. All subjects were
biopsied based on an initial elevated PSA value and/or suspicious
DRE result. A distribution of the ARCHITECT Total PSA results is
presented in the following table:

5
 Distribution of Results from ARCHITECT Total PSA
PSA ≤ 4.0 PSA > 4.0 Total
DRE-b 32 319 351
6.0% 60.1% 66.1%
DRE+a 96 84 180
18.1% 15.8% 33.9%
Total 128 403 531
24.1% 75.9% 100.0%
Note: 499 patients tested positive by DRE and/or PSA.
a
DRE+: Digital Rectal Examination (Suspicious for cancer)
b
DRE-: Digital Rectal Examination (Not suspicious for cancer)

The positive predictive values for various combinations of DRE and

PSA are presented graphically in the figure below and table below.

These results demonstrate that the ARCHITECT Total PSA assay

yields equivalent results compared to those obtained using the AxSYM
Total PSA assay.
Serum PSA concentrations, regardless of the value, should not be
interpreted as definitive evidence for the presence or absence of
prostate cancer. In addition, PSA testing should be done in conjunction
with DRE because PSA and DRE together detected the greatest number
of cancers. Prostatic biopsy is required for the diagnosis of cancer.
Positive Predictive Values EXPECTED VALUES
Positive Number of Subjects [Values developed for the ARCHITECT i2000 analyzer.]
Predictive with Cancer/ The distribution of ARCHITECT Total PSA values determined in 2,287
Detection Value Number of Subjects specimens is shown in the following table.
Method (%)* Suspicious for Cancer
Distribution of ARCHITECT Total PSA Values
DRE+ 37.2 67/180
(30.1-44.7) Percent (%)
PSA > 4.0 39.2 158/403 Number of 0-4.0 >4.0-10 >10-30 >30-60 >60
(34.4-44.2) Subjects (ng/mL) (ng/mL) (ng/mL) (ng/mL) (ng/mL)
PSA ≤ 4.0 and DRE+ 13.5 13/96 Apparently Females 296 100.0 0.0 0.0 0.0 0.0
Healthy Males Ages 99 100.0 0.0 0.0 0.0 0.0
(7.4-22.0)
Subjects 40 to 49
PSA > 4.0 and DRE- 32.6 104/319
Males Ages 120 97.5 2.5 0.0 0.0 0.0
(27.5-38.0)
50 to 59
PSA > 4.0 and DRE+ 64.3 54/84
Males Ages 123 93.5 6.5 0.0 0.0 0.0
(53.1-74.4) 60 to 69
PSA > 4.0 or DRE+ 34.3 171/499 Males Ages 124 91.9 7.3 0.8 0.0 0.0
(30.1-38.6) 70 to 79
* 95% Confidence Interval (Lower Limit - Upper Limit)
Non-
Cancers were detected in 177 of the 531 subjects. The overall cancer malignant BPH 352 42.6 42.3 12.8 1.1 1.1
detection rate was 96.6% (171/177) when at least one test was Disease
suspicious, 30.5% (54/177) when both tests were suspicious, 58.8% Cirrhosis 89 94.4 3.4 1.1 0.0 1.1
(104/177) for PSA alone, and 7.3% (13/177) for DRE alone. Genitourinary 151 90.7 7.3 1.3 0.7 0.0
Prostatitis 142 46.5 40.1 11.3 1.4 0.7
CORRELATION Renal 140 90.0 5.7 2.9 1.4 0.0
To demonstrate that the ARCHITECT Total PSA assay results are
comparable to the results from the AxSYM Total PSA assay, a Malignant Prostate 94 46.8 30.9 17.0 1.1 4.3
least squares linear regression analysis was performed comparing Disease Stage A
the PSA values from both assays for 1,798 clinical specimens. The Prostate 166 30.1 44.0 23.5 0.6 1.8
analysis yielded a correlation coefficient of 0.987, a slope of 1.06, Stage B
and a Y-intercept of 0.344 for the specimens covering the range up
Prostate 141 26.2 22.7 29.1 12.8 9.2
to 100 ng/mL, as shown in the following figure: Stage C
Prostate 95 15.8 12.6 32.6 10.5 28.4
Stage D
Genitourinary 155 92.9 3.9 1.9 0.6 0.6

6
In this study, 95.5% of the specimens from apparently healthy male Analytical
subjects (n=466) had values of 4.0 ng/mL or less. The analytical sensitivity of the ARCHITECT Total PSA assay was
It is recommended that each laboratory establish its own expected calculated to be less than 0.008 ng/mL. This sensitivity is defined as
reference range for the population of interest. the concentration at two standard deviations above the mean RLU for
The malignant disease portion of the distribution table is derived the ARCHITECT Total PSA MasterCheck Level 0 and represents the
primarily from carcinoma patients representing both active (clinical lowest measurable concentration of total PSA that can be distinguished
evidence of disease progression) and inactive (no clinical evidence from zero.
of disease progression) disease states. When changing PSA assay
methods in the course of monitoring a patient, additional sequential Analytical Specificitya
testing should be carried out to confirm baseline values. The analytical specificity of the ARCHITECT Total PSA assay was
determined by testing sera containing the following compounds. These
SPECIFIC PERFORMANCE CHARACTERISTICS compounds showed less than or equal to 10% interference in the
Precisiona ARCHITECT Total PSA assay at the levels indicated.
Architect Total PSA assay precision is ≤ 8%. Precision was determined INTERFERING SUBSTANCES
as described in the National Committee for Clinical Laboratory
Standards (NCCLS) Protocol EP5-A.32 Six samples, consisting of three Test Compound Concentration
serum based panels and three total PSA controls, were assayed using Bilirubin 20 mg/dL
three instruments in replicates of two at two separate times per day Hemoglobin 500 mg/dL
for twenty days (n=80 for each sample), using a single lot of reagents Total Protein 2.0 g/dL & 12.0 g/dL
and a single calibration. Data from this study are summarized in the Prostatic Acid Phosphatase 1000 ng/mL
following table.* Triglycerides 3000 mg/dL
Hytrin 10 μg/mL
Reproducibility of ARCHITECT Total PSA Proscar 25 μg/mL
Flomax 1 μg/mL
Mean
Instru- Total PSA Within Run Total CHEMOTHERAPEUTIC AGENTS
Sample ment (ng/mL) SD %CV SD %CV Test Compound Concentration
Low Control 1 0.498 0.0087 1.8 0.0109 2.2 Cyclophosphamide 700 μg/mL
2 0.511 0.0203 4.0 0.0237 4.6 Diethylstilbestrol 2 μg/mL
3 0.504 0.0131 2.6 0.0194 3.9 Doxorubicin-HCI 16 μg/mL
Medium Control 1 4.030 0.1036 2.6 0.1107 2.7 Estramustine Phosphate 200 μg/mL
2 4.104 0.1517 3.7 0.1836 4.5 Flutamide 10 μg/mL
Goserelin Acetate 100 ng/mL
3 4.101 0.1218 3.0 0.1714 4.2
Lupron 100 μg/mL
High Control 1 24.565 0.7187 2.9 0.8121 3.3 Megestrol Acetate 90 μg/mL
2 24.558 1.0663 4.3 1.1691 4.8 Methotrexate 30 μg/mL
3 24.210 0.7742 3.2 1.5808 6.5
Carryovera
Panel 1 1 4.130 0.1129 2.7 0.3230 7.8
No detectable carryover (less than 0.5 PPM) was observed when a
2 4.109 0.1479 3.6 0.1665 4.1
sample containing 16,791 ng/mL of PSA was assayed. However, under
3 4.139 0.1042 2.5 0.2099 5.1 circumstances where a PSA assay is performed following >230 tests
Panel 2 1 49.191 1.6925 3.4 1.8405 3.7 of ARCHITECT B12, carryover of PSA due to protein build up on the
2 46.943 2.0034 4.3 2.6271 5.6 sample pipettor probe may exceed 0.5 PPM.
3 47.770 1.5792 3.3 3.4934 7.3 To maintain optimum system performance and reduce the potential
Panel 3 1 66.952 2.0804 3.1 4.1157 6.1 of carryover due to protein build up on the sample pipettor probe, it
2 62.631 3.1461 5.0 3.2269 5.2 is important to follow the routine maintenance procedures defined
in Section 9 of the ARCHITECT System Operations Manual, or,
3 61.632 1.5634 2.5 5.5307 9.0
for troubleshooting information refer to the ARCHITECT System
* Representative performance data are shown. Results obtained at Operations Manual, Section 10.
individual laboratories may vary.
High Dose Hooka
MEASUREMENT RANGE High dose hook is a phenomenon whereby very high level specimens
The measurement (reportable) range of the ARCHITECT Total PSA may read within the dynamic range of the assay. For the ARCHITECT
assay is 0.008 ng/mL to 100 ng/mL, as defined by the analytical Total PSA assay, no high dose hook effect was observed when samples
sensitivity lower limit and the upper limit of the extended calibration containing up to approximately 48,000 ng/mL of PSA were assayed.
range. For patient specimens with a Total PSA assay value exceeding a
[Values developed for the ARCHITECT i2000 analyzer.]
100 ng/mL refer to the sample dilution procedures section of this Accuracy by Correlation
package insert.
The ARCHITECT Total PSA assay reagents were compared on the
Recoverya ARCHITECT i2000/ i2000SR and the ARCHITECT i1000SR platforms.
Known concentrations of serum PSA were added to ten normal The results of specimen testing are shown below.
human serum samples. Each sample was spiked at a low and a Statistical Number of Correlation
high level. The concentration of total PSA was determined using the Method Observations Intercept Slope Coefficient
ARCHITECT Total PSA assay and the resulting percent recovery was Least 151 -0.06 1.05 0.996
calculated. The mean recovery was 95.9% with values ranging from Squares
89.8% to 99.6%.
Sensitivitya Passing- 151 -0.03 1.04 0.996
Functional Bablok*
Functional sensitivity is defined as the lowest concentration that can be * A linear regression method with no special assumptions regarding the
measured with an inter-assay coefficient of variation (CV) less than or distribution of the samples and the measurement errors.35
equal to 20%. The calculated %CV for one reagent lot from all sites was
plotted against the mean concentration of each panel. A parametric In this evaluation, serum specimens tested ranged from 0.046 ng/mL
curve was fitted through the data, and the functional sensitivity was to 81.710 ng/mL, by the i1000SR platform.
determined to be less than 0.05 ng/mL, which corresponded to less
than 20% CV on the fitted curve.

7
BIBLIOGRAPHY 23. Schroff RW, Foon KA, Beatty SM, et al. Human Anti-Murine
1. McCormack RT, Rittenhouse HG, Finlay JA, et al. Molecular Forms Immunoglobulin Responses in Patients Receiving Monoclonal
of Prostate-Specific Antigen and the Human Kallikrein Gene Family: Antibody Therapy. Cancer Res 1985;45:879–85.
A New Era. Urology 1995;45:729-44. 24. Boscato LM, Stuart MC. Heterophilic Antibodies: A Problem for
2. Graves HCB. Nonprostatic Sources of Prostate-Specific Antigen: All Immunoassays. Clin Chem 1988;34(1):27-33.
A Steroid Hormone-Dependent Phenomenon? Clin Chem 25. Chan DW, Bruzek DJ, Oesterling JE, et al. Prostate-Specific Antigen
1995;41:7-9. as a Marker for Prostatic Cancer: A Monoclonal and a Polyclonal
3. Kuriyama M, Wang MC, Papsidero LD, et al. Quantitation of Prostate- Immunoassay Compared. Clin Chem 1987;33:1916-20.
Specific Antigen in Serum by a Sensitive Enzyme Immunoassay. 26. Hortin GL, Bahnson RR, Daft M, et al. Differences in Values
Cancer Res 1980;40:4658-62. Obtained with 2 Assays of Prostate Specific Antigen. J Urol
4. Oesterling JE. Prostate Specific Antigen: A Critical Assessment of 1988;139:762–5.
the Most Useful Tumor Marker for Adenocarcinoma of the Prostate. 27. Morgan WR, Zincke H, Rainwater LM, et al. Prostate Specific
J Urol 1991;145:907-23. Antigen Values after Radical Retropubic Prostatectomy for
5. Kantoff PW, Talcott JA. The Prostate Specific Antigen. Its Use as Adenocarcinoma of the Prostate: Impact of Adjuvant Treatment
a Tumor Marker for Prostate Cancer Hematol Oncol Clin N Amer (Hormonal and Radiation). J Urol 1991;145:319–23.
1994;8:555-72. 28. Chybowski FM, Bergstralh EJ, Oesterling JE. The Effect of Digital
6. Partin AW, Oesterling JE. The Clinical Usefulness of Prostate Rectal Examination on the Serum Prostate Specific Antigen Levels.
Specific Antigen: Update 1994. J Urol 1994;152:1358-68. J Urol 1992;148:83–6.
7. Bunting S. A Guide to the Interpretation of Serum Prostate Specific 29. Yuan JJJ, Coplen DE, Petros JA, et al. Effects of Rectal Examination,
Antigen Levels. Clin Biochem 1995;28:221-41. Prostatic Massage, Ultrasonography and Needle Biopsy on Serum
8. Christensson A, Laurell C-B, Lilja H. Enzymatic Activity of Prostate- Prostate Specific Antigen Levels. J Urol 1992;147:810–4.
Specific Antigen and its Reactions with Extracellular Serine 30. Tchetgen M-B, Song JT, Strawderman M, et al. Ejaculation
Proteinase Inhibitors. Eur J Biochem 1990;194:755-63. Increases the Serum Prostate-Specific Antigen Concentration.
9. Stenman U-H, Leinonen J, Alfthan H, et al. A Complex Between Urology 1996;47:511–6.
Prostate-Specific Antigen and a1-Antichymotrypsin is the Major 31. Stenman U-H, Leinonen J, Zhang W-M. Problems in the
Form of Prostate-Specific Antigen in Serum of Patients with Determination of Prostate Specific Antigen. Eur J Clin Chem
Prostatic Cancer: Assay of the Complex Improves Clinical Sensitivity Biochem 1996;34:735–40.
for Cancer. Cancer Res 1991;51:222-6. 32. NCCLS. Evaluation of Precision Performance of Clinical Chemistry
10. Parker SL, Tong T, Bolden S, et al. Cancer Statistics, 1997. CA Devices; Approved Guideline. NCCLS document EP5-A (ISBN
Cancer J Clin 1997;47:5-27. 1-56238-368-X). NCCLS, 940 West Valley Road, Suite 1400, Wayne,
11. Gerber GS, Chodak GW. Routine Screening for Cancer of the PA 19087-1898, USA, 1999.
Prostate (Review). J Natl Ca Inst 1991;83:329–35. 33. Watt KWK, Lee P-J, M’Timkulu T, et al. Human Prostate-Specific
12. Lee F, Littrup PJ, Torp-Pedersen ST, et al. Prostate Cancer: Antigen: Structural and Functional Similarity with Serine Proteases.
Comparison of Transrectal US and Digital Rectal Examination for Proc Natl Acad Sci USA 1986;83:3166–70.
Screening. Radiology 1988;168:389–94. 34. Belanger A, van Halbeek H, Graves HCB, et al. Molecular Mass
13. Cooner WH, Mosely BR, Rutherford CL, et al. Prostate Cancer and Carbohydrate Structure of Prostate Specific Antigen: Studies
Detection in a Clinical Urological Practice by Ultrasonography, for Establishment of an International PSA Standard. Prostate
Digital Rectal Examination and Prostate Specific Antigen. J Urol 1995;27:187–97.
1990;143:1146–54. 35. Passing H, Bablok W. A New Biometrical Procedure for Testing the
14. Catalona WJ, Richie JP, Ahmann FR, et al. Comparison of Digital Equality of Measurements from Two Different Analytical Methods.
Rectal Examination and Serum Prostate Specific Antigen in the J Clin Chem. Clin Biochem 1983;21;709-20.
Early Detection of Prostate Cancer: Results of a Multicenter Clinical
Trial of 6,630 Men. J Urol 1994;151:1283-90. All trademarks are properties of their respective owners.
15. Crawford ED, DeAntoni EP, Etzioni R, et al. Serum Prostate-Specific For additional product information, please contact your local customer
Antigen and Digital Rectum Examination for Early Detection of service organization.
Prostate Cancer in a National Community-Based Program. Urology
1996;47:863–9.
16. American Urological Association - Early Detection of Prostate Abbott Ireland
Cancer Policy Statement. Board of Directors Minutes 1992. Diagnostics Division
17. Mettlin C, Jones G, Averette H, et al. Defining and Updating the Finisklin Business Park
American Cancer Society Guidelines for the Cancer-Related Sligo
Checkup: Prostate and Endometrial Cancers. CA-A Cancer Journal Ireland
for Clinicians 1993;43:42–6.
+ 353-71-9171712
18. Walther PJ. Prostate Cancer Screening. Why the Controversy?
Surg Oncol Clin NA 1995;4:315-34. June 2007
19. Jacobson JO. Can Screening for Early-Stage Prostate Cancer be © 2006, 2007 Abbott / ARCHITECT Total PSA
Rationalized? Hematol Oncol Clinics NA 1996;10:549-64.
20. Woodrum D, French C, Shamel LB. Stability of Free Prostate-
Specific Antigen in Serum Samples Under a Variety of Sample
Collection and Sample Storage Conditions. Urology (Suppl. 6A)
1996;48:33-9.
21. Piironen T, Pettersson K, Suonpää M, et al. In Vitro Stability of Free
Prostate-Specific Antigen (PSA) and Prostate-Specific Antigen
(PSA) Complexed to a1-Antichymotrypsin in Blood Samples.
Urology (Suppl. 6A) 1996;48:81–6.
22. Primus FJ, Kelley EA, Hansen HJ, et al. “Sandwich”-Type
Immunoassay of Carcinoembryonic Antigen in Patients Receiving
Murine Monoclonal Antibodies for Diagnosis and Therapy. Clin
Chem 1988;34:261–4.