Effect of Marathon Running on Total and Free Serum Prostate-Specific Antigen Concentrations

Abstract Context.—Prostate-specific antigen (PSA) is an important tumor marker for the most frequently diagnosed cancer in the United States. A major limitation of this marker is falsely elevated results in patients who are found not to have prostate cancer. The effects of vigorous physical exertion on PSA concentrations are controversial. Objective.—To determine the effects of marathon running on PSA levels. Design.—Measurement of total and free PSA levels in the sera of participants in a marathon before and within 4 and 24 hours after the race. Results.—None of the participants had elevated total PSA levels before the race. Although we found no statistically significant changes in average total or free PSA concentrations at either time point, after the marathon, 2 (11%) of 18 runners had total PSA concentrations outside the standard reference range. Changes in total PSA levels did not correlate with age or prerace PSA concentrations. Free PSA levels were not statistically significantly changed after the race and did not allow a reliable determination of exercise-induced PSA elevations. Conclusions.—Although it may not be necessary for men to abstain from exercise involving running before blood draws for PSA analysis, elevated PSA concentrations may be observed in some individuals after participation in a major sporting event. In these cases, repeat measurements should be considered at a time significantly removed from such exercise.

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The Combination of Human Glandular Kallikrein and Free Prostate-specific Antigen (PSA) Enhances Discrimination Between Prostate Cancer and Benign Prostatic Hyperplasia in Patients with Moderately Increased Total PSA

Clinical Chemistry ◽

10.1093/clinchem/45.11.1960 ◽

1999 ◽

Vol 45 (11) ◽

pp. 1960-1966 ◽

Cited By ~ 68

Author(s):

Angeliki Magklara ◽

Andreas Scorilas ◽

William J Catalona ◽

Eleftherios P Diamandis

Keyword(s):

Prostate Cancer ◽

Benign Prostatic Hyperplasia ◽

Prostate Specific Antigen ◽

Prostatic Carcinoma ◽

Specific Antigen ◽

Area Under The Curve ◽

Prostatic Hyperplasia ◽

Free Psa ◽

Glandular Kallikrein ◽

Total Psa

Abstract Background: Prostate-specific antigen (PSA) is the most reliable tumor marker available and is widely used for the diagnosis and management of prostate cancer. Unfortunately, PSA cannot distinguish efficiently between benign and malignant disease of the prostate, especially within the range of 4–10 μg/L. Among the refinements developed to enhance PSA specificity is the free/total PSA ratio, which is useful in discriminating between the two diseases within the diagnostic “gray zone”. Recent data indicate that human glandular kallikrein (hK2), a protein with high homology to PSA, may be an additional serum marker for the diagnosis and monitoring of prostate cancer. Methods: We analyzed 206 serum samples (all before treatment was initiated) from men with histologically confirmed benign prostatic hyperplasia (n = 100) or prostatic carcinoma (n = 106) with total PSA in the range of 2.5–10 μg/L. Total and free PSA and hK2 were measured with noncompetitive immunological procedures. Statistical analysis was performed to investigate the potential utility of the various markers or their combinations in discriminating between benign prostatic hyperplasia and prostatic carcinoma. Results: hK2 concentrations were not statistically different between the two groups of patients. There was a strong positive correlation between hK2 and free PSA in the whole patient population. hK2/free PSA ratio (area under the curve = 0.69) was stronger predictor of prostate cancer than the free/total PSA ratio (area under the curve = 0.64). At 95% specificity, the hK2/free PSA ratio identified 30% of patients with total PSA between 2.5–10 μg/L who had cancer. At 95% specificity, the hK2/free PSA ratio identified 25% of patients with total PSA between 2.5 and 4.5 μg/L who had cancer. Conclusions: Our data suggest that hK2 in combination with free and total PSA can enhance the biochemical detection of prostate cancer in patients with moderately increased total PSA concentrations. More specifically, the hK2/free PSA ratio appears to be valuable in identifying a subset of patients with total PSA between 2.5 and 4.5 μg/L who have high probability of cancer and who should be considered for biopsy.

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Dual-label one-step immunoassay for simultaneous measurement of free and total prostate-specific antigen concentrations and ratios in serum

Clinical Chemistry ◽

10.1093/clinchem/41.8.1115 ◽

1995 ◽

Vol 41 (8) ◽

pp. 1115-1120 ◽

Cited By ~ 110

Author(s):

K Mitrunen ◽

K Pettersson ◽

T Piironen ◽

T Björk ◽

H Lilja ◽

...

Keyword(s):

Prostate Specific Antigen ◽

Simultaneous Measurement ◽

Solid Phase ◽

Characteristic Curve ◽

Specific Antigen ◽

Sample Volume ◽

Free Psa ◽

One Step ◽

Total Psa ◽

Dual Label

Abstract We developed a simple one-step dual-label immunoassay for simultaneous measurement of the free, noncomplexed form of prostate-specific antigen (PSA) and total PSA. The assay is based on time-resolved fluorescence and includes a stable fluorescent chelate of Eu to label a monoclonal antibody (mAb) that detects only free PSA, whereas a second mAb labeled with a fluorescent chelate of Tb provides equimolar detection of both free PSA and PSA complexed to alpha 1-antichymotrypsin. A third mAb on a solid phase captures the free and complexed forms of PSA in an equimolar fashion. The simultaneous measurement of the free-to-total PSA ratio (F/T) with the one-step dual assay is not sensitive to variations in the sample volume. The discrimination between benign prostatic hyperplasia and prostate cancer patients, i.e., the area under the receiver-operating characteristic curve, increased from 0.64 (total PSA assay) to 0.78 and 0.81 when the F/T ratio was measured with single and dual assays, respectively.

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Reference Reagents for Prostate-specific Antigen (PSA): Establishment of the First International Standards for Free PSA and PSA (90:10)

Clinical Chemistry ◽

10.1093/clinchem/46.9.1310 ◽

2000 ◽

Vol 46 (9) ◽

pp. 1310-1317 ◽

Cited By ~ 62

Author(s):

Brian Rafferty ◽

Peter Rigsby ◽

Matthew Rose ◽

Thomas Stamey ◽

Rose Gaines Das

Keyword(s):

Confidence Interval ◽

Prostate Specific Antigen ◽

Recombinant Dna ◽

Collaborative Study ◽

Specific Antigen ◽

International Standards ◽

Serum Samples ◽

International Standard ◽

Free Psa ◽

Total Psa

Abstract Background: Prostate-specific antigen (PSA) measurements in serum by immunoassay are widely used in the screening, diagnosis, and monitoring of patients with prostate cancer although the lack of common reference reagents has led in the past to wide differences in estimates. We report here the results of a WHO international collaborative study in which two preparations of PSA representative of the main immunoreactive components in serum, free PSA and PSA 90:10, and a preparation of recombinant DNA-derived PSA were assessed as potential standards for the calibration of diagnostic immunoassays for PSA. Methods: Coded vials of the candidate materials and serum preparations containing PSA in the clinically important range were provided to the 10 laboratories in the study, and participants were asked to perform PSA assays currently in use in their laboratories. Data from 89 immunoassays by 26 different method-laboratory combinations were contributed to the study and analyzed centrally at the National Institute for Biological Standards and Control. Results: Potency estimates of the preparations relative to the in-house calibrators were in good agreement with the target value of 1 μg of total PSA/vial, the preparation of free PSA giving 1.10 μg/vial (95% confidence interval, 0.99–1.21 μg/vial) and PSA 90:10, 1.11 μg/vial (95% confidence interval, 1.04–1.18 μg/vial). No immunoreactivity was detected in ampoules containing the recombinant material. Use of a common standard of PSA 90:10 significantly reduced the between-laboratory geometric coefficients of variation for serum samples included in the study and gave a much narrower range of potency estimates. Conclusions: The preparation of free PSA was established by WHO as the First International Standard for PSA (free) with an assigned content of 1 μg of total PSA per vial. In addition, the preparation of bound PSA was established as the First International Standard for PSA (90:10) with an assigned content of 1 μg of total PSA per vial.

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Determination of Non-α1-Antichymotrypsin-complexed Prostate-specific Antigen as an Indirect Measurement of Free Prostate-specific Antigen: Analytical Performance and Diagnostic Accuracy

Clinical Chemistry ◽

10.1373/49.6.887 ◽

2003 ◽

Vol 49 (6) ◽

pp. 887-894 ◽

Cited By ~ 12

Author(s):

Sebastian Wesseling ◽

Carsten Stephan ◽

Axel Semjonow ◽

Michael Lein ◽

Brigitte Brux ◽

...

Keyword(s):

Prostate Specific Antigen ◽

Sensitivity And Specificity ◽

Specific Antigen ◽

Roc Curves ◽

Indirect Measurement ◽

Free Psa ◽

Specificity And Sensitivity ◽

Diagnostic Sensitivity And Specificity ◽

Total Psa

Abstract Background: A new assay measures prostate-specific antigen (PSA) not complexed to α1-antichymotrypsin (nACT-PSA) after removing PSA complexed to ACT by use of anti-ACT antibodies. We evaluated nACT-PSA and its ratio to total PSA (tPSA) as alternatives to free PSA (fPSA) and its ratio to tPSA in differentiating prostate cancer (PCa) and benign prostatic hyperplasia (BPH) in patients with tPSA of 2–20 μg/L. Methods: PSA in serum of 183 untreated patients with PCa and 132 patients with BPH was measured retrospectively on the chemiluminescence immunoassay analyzer LIAISON® (Byk-Sangtec Diagnostica) with the LIAISON tPSA and LIAISON fPSA assays. The nACT-PSA fraction was determined with a prototype assay measuring the residual PSA after precipitation of ACT-PSA with an ACT-precipitating reagent. Results:nACT-PSA was higher than fPSA in samples with fPSA concentrations <1 μg/L but lower in samples with >1 μg/L fPSA. The median ratios of fPSA/tPSA and of nACT-PSA/tPSA were significantly different between patients with BPH and PCa (19.4% vs 12.2% and 17.4% vs 13.0%, respectively). Within the tPSA ranges tested (2–20, 2–10, and 4–10 μg/L), areas under the ROC curves for the fPSA/tPSA ratios were significantly larger than those for nACT-PSA/tPSA. In the tPSA ranges <10 μg/L, the areas under the ROC curves for fPSA/tPSA were significantly larger than those for tPSA, whereas the areas for nACT-PSA/tPSA were not. At decision limits for 95% sensitivity and specificity, both ratios significantly increased specificity and sensitivity, respectively, compared with tPSA, but the fPSA/tPSA ratio showed higher values. Conclusions: nACT-PSA and its ratio to tPSA provide lower diagnostic sensitivity and specificity than fPSA/tPSA. The fPSA/tPSA ratio represents the state-of-the-art method for differentiating between PCa and BPH.

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Effect of the Ratio of Free to Total Prostate-specific Antigen on Interassay Variability in Proficiency Test Samples

Clinical Chemistry ◽

10.1093/clinchem/45.8.1181 ◽

1999 ◽

Vol 45 (8) ◽

pp. 1181-1189 ◽

Cited By ~ 4

Author(s):

M Pat Fox ◽

Andrew A Reilly ◽

Erasmus Schneider

Keyword(s):

Prostate Specific Antigen ◽

Proficiency Test ◽

Seminal Fluid ◽

Specific Antigen ◽

Free Form ◽

Sample Mean ◽

Substantial Impact ◽

Free Psa ◽

Total Prostate Specific Antigen ◽

Total Psa

Abstract Background: Up to sevenfold differences were observed between total prostate-specific antigen (PSA) methods for New York State Proficiency Test samples prepared with seminal fluid PSA in human female serum. Because the PSA was mainly in its free form under these conditions, we wanted to determine whether a defined mixture of free and complexed PSA would reduce the interassay differences. Methods: We prepared a series of five solutions of 60 g/L bovine serum albumin with 10 μg/L total PSA consisting of varied proportions of free, noncomplexible PSA, and α1-antichymotrypsin (ACT)-complexed PSA from 0% to 100%. Two hundred seventy laboratories measured the total PSA in these samples, and 16 laboratories also analyzed the samples for free PSA. The results were used to calculate free/total PSA ratios. Results: Interassay CVs for total PSA measurements were ∼7% at 10–15% free PSA but became gradually larger as the free/total PSA ratio increased. Measured free-PSA concentrations were similar within each sample (mean CV, 12%), and the results were relatively independent of the proportion of free PSA in the samples. Twofold discrepancies between actual and expected ratios were observed with some methods at 100% free PSA and to a lesser degree at 30% free PSA. At 100% free PSA, the relatively higher total-PSA values measured by nonequimolar methods yielded low free/total PSA ratios of 50–60%. In contrast, the lower total PSA values obtained by equimolar methods yielded ratios close to the expected 100%. Conclusions: Preparing proficiency test samples with a 10:90 mixture of free, noncomplexible PSA:PSA-ACT is a viable alternative to the use of seminal fluid PSA. Furthermore, the method used to measure total PSA may have a substantial impact on the calculated proportion of free PSA and hence may have clinical relevance.

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Comparison of prostate-specific antigen (PSA) measured by four combinations of free PSA and total PSA assays

Clinical Chemistry ◽

10.1093/clinchem/43.9.1588 ◽

1997 ◽

Vol 43 (9) ◽

pp. 1588-1594 ◽

Cited By ~ 23

Author(s):

Ralf Junker ◽

Burkhard Brandt ◽

Christian Zechel ◽

Gerd Assmann

Keyword(s):

Prostate Specific Antigen ◽

Patient Population ◽

Specific Antigen ◽

Prostate Hyperplasia ◽

Predictive Values ◽

Negative Results ◽

Free Psa ◽

Gray Area ◽

Total Psa ◽

Benign Prostate

Abstract We compared prostate-specific antigen (PSA) assay systems [i.e., free PSA (f-PSA) and the corresponding total PSA (t-PSA) assay] from four different manufacturers as well as the f-PSA/t-PSA ratios with regard to their ability to discriminate between benign prostate hyperplasia (BPH) and prostate cancer (PCA). ROC analysis showed similar areas under the curves (AUCs) with different assay systems. For the entire patient population the AUCs of the f-PSA/t-PSA ratio were not or slightly increased compared with the sole measurement of t-PSA (t-PSA, 0.792–0.820; f-PSA/t-PSA ratio, 0.685–0.859). In contrast, for only those patients who showed t-PSA concentrations within the diagnostic gray area of 4–25 μg/L t-PSA, the AUCs were greater for the f-PSA/t-PSA ratio than for measurement of t-PSA alone (t-PSA, 0.608–0.647; f-PSA/t-PSA ratio, 0.690–0.806). These results were confirmed by the predictive values of the negative results (NPVs) of the t-PSA assays and the f-PSA/t-PSA ratios (assay thresholds corresponding to a 95% detection limit). Compared with the sole t-PSA measurement there was no mentionable increase in the NPVs due to the f-PSA/t-PSA ratio for the entire patient population, but an increase up to 49% when limited to t-PSA concentrations within 4–25 μg/L. We therefore conclude that the f-PSA/t-PSA ratio may be helpful for differential diagnosis of BPH and PCA within the diagnostic gray area of 4–25 μg/L t-PSA.

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Novel immunoassay for the measurement of complexed prostate-specific antigen in serum

Clinical Chemistry ◽

10.1093/clinchem/44.6.1216 ◽

1998 ◽

Vol 44 (6) ◽

pp. 1216-1223 ◽

Cited By ~ 83

Author(s):

W Jeffrey Allard ◽

Zeqi Zhou ◽

Kwok K Yeung

Keyword(s):

Prostate Cancer ◽

Monoclonal Antibody ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Binding Properties ◽

Prostate Disease ◽

Free Psa ◽

Total Psa ◽

Benign Prostate ◽

Artificial Mixtures

Abstract Serum prostate-specific antigen (PSA) is an effective diagnostic tool for detection of prostate cancer (CaP) at an early and potentially curable stage, but specificity is low. Studies have shown that the proportion of serum PSA complexed with α-1-antichymotrypsin (ACT) is higher in men with CaP than in men with benign prostate disease. We developed a novel immunoassay for complexed PSA based on the unique binding properties of a monoclonal antibody that fails to bind free PSA in the presence of antibodies specific for free PSA. The assay measured mixtures of free and complexed PSA accurately, and the measured values of free + complexed PSA in artificial mixtures and in patient sera were equivalent to the measured value of total PSA. Both the serum concentration and the proportion of complexed PSA was substantially higher in patients with CaP compared with patients with benign prostate disease. The cPSA assay may have utility in improving specificity in screening for prostate cancer.

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1265: International Multi-Center Comparison of Complexed Prostate Specific Antigen (CPSA) with Total PSA, Percent CPSA, and Percent free PSA

The Journal of Urology ◽

10.1016/s0022-5347(18)38490-8 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 333-333

Author(s):

Bruce Track ◽

M. Craig Miller ◽

Huntington Valley ◽

Carol D. Cheli ◽

Michael K. Brawer ◽

...

Keyword(s):

Prostate Specific Antigen ◽

Specific Antigen ◽

Free Psa ◽

Total Psa

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Comparison of Fresh Frozen Serum to Proficiency Testing Material in College of American Pathologists Surveys: α-Fetoprotein, Carcinoembryonic Antigen, Human Chorionic Gonadotropin, and Prostate-Specific Antigen

Archives of Pathology & Laboratory Medicine ◽

10.5858/2005-129-331-coffst ◽

2005 ◽

Vol 129 (3) ◽

pp. 331-337

Author(s):

William E. Schreiber ◽

David B. Endres ◽

Geraldine A. McDowell ◽

Glenn E. Palomaki ◽

Ronald J. Elin ◽

...

Keyword(s):

Carcinoembryonic Antigen ◽

Prostate Specific Antigen ◽

Proficiency Testing ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Peer Group ◽

Specific Antigen ◽

Free Psa ◽

Fresh Frozen ◽

Total Psa

Abstract Context.—Most proficiency testing materials (PTM) contain an artificial matrix that may cause immunoassays to perform differently with this material than with clinical samples. We hypothesized that matrix effects would be reduced by using fresh frozen serum (FFS). Objective.—To compare the performance of an FFS pool to standard PTM for measurement of α-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin (hCG), and prostate-specific antigen (PSA). Design.—One FFS specimen and 4 different admixtures of PTM were distributed in the 2003 College of American Pathologists K/KN-A (for α-fetoprotein, carcinoembryonic antigen, hCG, and total and free PSA) and C-C (hCG only) Surveys. Participants.—The number of laboratories that participated in the surveys varied from a low of 288 (free PSA, K/KN-A Survey) to a high of 2659 (hCG, C-C Survey). Main Outcome Measures.—Method imprecision and method bias were compared between the FFS specimen and the standard PTM specimen with the closest value. Method imprecision was determined by calculating the coefficients of variation for each method and for all methods combined. Bias was defined as the proportional difference between peer-group mean and the median of all method means. Results.—The FFS specimen gave significantly higher imprecision than PTM for the analytes α-fetoprotein, carcinoembryonic antigen, total PSA, and free PSA. For hCG, no substantial imprecision differences were observed in both surveys. Bias was significantly greater for the α-fetoprotein, carcinoembryonic antigen, and total PSA assays and significantly lower for the hCG and free PSA assays when comparing the FFS with the PTM. Conclusions.—Fresh frozen serum did not provide consistently lower imprecision or bias than standard PTM in a survey of commonly ordered tumor markers.

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