scholarly journals Between-Method Differences in Prostate-Specific Antigen Assays Affect Prostate Cancer Risk Prediction by Nomograms

2011 ◽  
Vol 57 (7) ◽  
pp. 995-1004 ◽  
Author(s):  
Carsten Stephan ◽  
Kerstin Siemßen ◽  
Henning Cammann ◽  
Frank Friedersdorff ◽  
Serdar Deger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Risk Prediction ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Roc Curves ◽  
Median Percentage ◽  
Free Psa ◽  
Different Types ◽  
Total Psa

BACKGROUND To date, no published nomogram for prostate cancer (PCa) risk prediction has considered the between-method differences associated with estimating concentrations of prostate-specific antigen (PSA). METHODS Total PSA (tPSA) and free PSA were measured in 780 biopsy-referred men with 5 different assays. These data, together with other clinical parameters, were applied to 5 published nomograms that are used for PCa detection. Discrimination and calibration criteria were used to characterize the accuracy of the nomogram models under these conditions. RESULTS PCa was found in 455 men (58.3%), and 325 men had no evidence of malignancy. Median tPSA concentrations ranged from 5.5 μg/L to 7.04 μg/L, whereas the median percentage of free PSA ranged from 10.6% to 16.4%. Both the calibration and discrimination of the nomograms varied significantly across different types of PSA assays. Median PCa probabilities, which indicate PCa risk, ranged from 0.59 to 0.76 when different PSA assays were used within the same nomogram. On the other hand, various nomograms produced different PCa probabilities when the same PSA assay was used. Although the ROC curves had comparable areas under the ROC curve, considerable differences were observed among the 5 assays when the sensitivities and specificities at various PCa probability cutoffs were analyzed. CONCLUSIONS The accuracy of the PCa probabilities predicted according to different nomograms is limited by the lack of agreement between the different PSA assays. This difference between methods may lead to unacceptable variation in PCa risk prediction. A more cautious application of nomograms is recommended.

scholarly journals 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

1999 ◽  
Vol 45 (11) ◽  
pp. 1960-1966 ◽  
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.

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

2003 ◽  
Vol 49 (6) ◽  
pp. 887-894 ◽  
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.

Evaluation of prostate cancer risk in men with PSA < 1.5.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 64-64
Author(s):  
Whitney N. Stanton ◽  
E. David Crawford ◽  
Paul Arangua ◽  
John Hoenemeyer ◽  
Francisco G. La Rosa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Clinical Information ◽  
Mrna Levels ◽  
Protein Biomarkers ◽  
Cancer Awareness ◽  
Free Psa ◽  
Increased Risk ◽  
Total Psa

64 Background: Prostate Specific Antigen (PSA) screening remains controversial primarily because of over detection and treatment. There is an unmet clinical need to identify patients at increased risk for high-grade (HG – Gleason Score ≥7) prostate cancer (PCa) since PSA has low sensitivity. Combining PSA with well-validated prostate cancer biomarkers (PCM) can improve risk assessment. We investigated the performance of three PCMs (phi – prostate health index, 4KScore, and SelectMDx) on patients with PSA levels < 1.5 ng/mL that represent a “safe zone” where risk of any PCa is rare Methods: 652 men were screened for PCa during the annual Prostate Cancer Awareness Week at the University of Colorado Hospital. This study was supported by Prostate Condition Education Council and the Schramm Foundation. phi is evaluated using p2PSA, total PSA, and free PSA in serum. Phi < 52.7 suggests absence of HG PCa. 4KScore incorporates four kallikrein protein biomarkers: total PSA, free PSA, intact PSA, human kallikrein protein, and clinical information. A 4KScore < 20% suggests absence of HG PCa. The SelectMDx post-DRE urine test measures mRNA levels of the homeobox C6 and distal-less homeobox 1 biomarkers. SelectMDx score of 0% indicates absence of HG PCa. Results: No patients with a PSA < 1.5 had SelectMDx > 0% and/or phi > 52.7. One patient had a 4KScore of 27%, indicating a risk for HG PCa. For patients with PSA between 1.5-3.99, 2.9% (4/135), 7.4% (4/54), and 2.3% (2/85) had positive phi, 4KScore, and SelectMDx results, respectively. Conclusions: Men with PSA <1.5 ng/mL are at very low risk for HG PCa. Men with PSA between 1.5-3.99 with positive PCM results may be referred for further evaluation. [Table: see text]

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

1998 ◽  
Vol 44 (6) ◽  
pp. 1216-1223 ◽  
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.

scholarly journals Definition of Outcome-Based Prostate-Specific Antigen (PSA) Thresholds for Advanced Prostate Cancer Risk Prediction

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3381
Author(s):  
Simona Ferraro ◽  
Marco Bussetti ◽  
Niccolò Bassani ◽  
Roberta Simona Rossi ◽  
Giacomo Piero Incarbone ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Risk Prediction ◽  
Advanced Prostate Cancer ◽  
Goodness Of Fit ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Lemeshow Test ◽  
Valid Estimate ◽  
Definition Of

We defined prostate-specific antigen (PSA) thresholds from a well calibrated risk prediction model for identifying and excluding advanced prostate cancer (PCa). We retrieved 902 biopsied patients with a pre-biopsy PSA determination (Roche assay). A logistic regression model predictive for PCa including the main effects [i.e., PSA, age, histological evidence of glandular inflammation (GI)] was built after testing the accuracy by calibration plots and Hosmer-Lemeshow test for goodness of fit. PSA thresholds were derived by assuming a diagnostic sensitivity of 95% (rule-out) and 80% (rule-in) for overall and advanced/poorly differentiated PCa. In patients without GI, serum PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa (defined as Gleason score ≥ 7 at biopsy), with a negative predictive value of 95.1% [95% confidence interval (CI): 83.0–98.7] and 88.8% (CI: 80.2–93.9), respectively, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) should address biopsy referral. In presence of GI, PSA did not provide a valid estimate for risk of advanced cancer because of its higher variability and the low pre-test probability of PCa. The proposed PSA thresholds may support biopsy decision except for patients with asymptomatic prostatitis who cannot be pre-biopsy identified.

Prostate-Specific Antigen (PSA) Isoform p2PSA in Combination with Total PSA and Free PSA Improves Diagnostic Accuracy in Prostate Cancer Detection

2010 ◽  
Vol 57 (6) ◽  
pp. 921-927 ◽  
Author(s):  
Flip H. Jansen ◽  
Ron H.N. van Schaik ◽  
Joep Kurstjens ◽  
Wolfgang Horninger ◽  
Helmut Klocker ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Diagnostic Accuracy ◽  
Prostate Specific Antigen ◽  
Cancer Detection ◽  
Specific Antigen ◽  
Prostate Cancer Detection ◽  
Free Psa ◽  
Total Psa

Clinical evaluation of free PSA/Total PSA (Prostate-specific Antigen) ratio in the diagnosis of prostate cancer

1997 ◽  
Vol 33 (8) ◽  
pp. 1226-1229 ◽  
Author(s):  
X Filella ◽  
J Alcover ◽  
R Molina ◽  
A Rodríguez ◽  
P Carretero ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Clinical Evaluation ◽  
Specific Antigen ◽  
Free Psa ◽  
Total Psa

scholarly journals Discrimination of Prostate Cancer from Benign Disease by Plasma Measurement of Intact, Free Prostate-specific Antigen Lacking an Internal Cleavage Site at Lys145-Lys146

2001 ◽  
Vol 47 (8) ◽  
pp. 1415-1423 ◽  
Author(s):  
Pauliina Nurmikko ◽  
Kim Pettersson ◽  
Timo Piironen ◽  
Jonas Hugosson ◽  
Hans Lilja
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Screening Program ◽  
Specific Antigen ◽  
Benign Disease ◽  
Free Psa ◽  
Plasma Measurement ◽  
Edta Plasma ◽  
Capture Antibody ◽  
Total Psa

Abstract Background: The proportion of free prostate-specific antigen (PSA) is higher in the sera of patients with benign prostatic hyperplasia compared with patients with prostate cancer (PCa). We developed an immunoassay that measures intact, free PSA forms (fPSA-I), but does not detect free PSA that has been internally cleaved at Lys145-Lys146 (fPSA-N), and investigated whether this form could discriminate patients with PCa from those without PCa. Methods: The assay for fPSA-I uses a novel monoclonal antibody (MAb) that does not detect PSA that has been internally cleaved at Lys145-Lys146. A MAb specific for free PSA was used as a capture antibody, and purified recombinant proPSA was used as a calibrator. The concentrations of fPSA-I, free PSA (PSA-F), and total PSA (PSA-T) were analyzed in EDTA-plasma samples (n = 276) from patients who participated in a screening program for PCa (PSA-T, 0.83–76.3 μg/L). Results: The detection limit of the fPSA-I assay was 0.035 μg/L. Both the measured concentrations of fPSA-I and the concentrations of fPSA-N (calculated as PSA-F − fPSA-I) provided statistically significant discrimination of the two clinical groups. By contrast, PSA-F did not discriminate between these groups. Each of the ratios fPSA-I/PSA-F, fPSA-N/PSA-T, and PSA-F/PSA-T separated cancer samples from noncancer samples in a statistically significant manner (P &lt;0.0001). The ratio fPSA-I/PSA-F was significantly higher in cancer (median, 59%) compared with noncancer samples (47%). Conclusions: The ratio fPSA-I/PSA-F is significantly higher in cancer compared with noncancer. The percentages of both fPSA-N/PSA-T and fPSA-I/PSA-F may provide interesting diagnostic enhancements alone or in combination with other markers and require further studies.

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