Clinical interpretation of prostate-specific antigen values: Type of applied cut-off value exceeds methods bias as the major source of variation

2019 ◽  
Vol 56 (2) ◽  
pp. 259-265 ◽  
Author(s):  
Lieke JJ Klinkenberg ◽  
Eef GWM Lentjes ◽  
Arjen-Kars Boer
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Clinical Decision ◽  
Relative Difference ◽  
Clinical Consequence ◽  
External Quality Assessment Scheme ◽  
Data Set ◽  
Annual Distribution

Background Prostate-specific antigen is the biochemical gold standard for the (early) detection and monitoring of prostate cancer. Interpretation of prostate-specific antigen is both dependent on the method and cut-off. The aim of this study was to examine the effect of method-specific differences and cut-off values in a national external quality assessment scheme (EQAS). Methods The Dutch EQAS for prostate-specific antigen comprised an annual distribution of 12 control materials. The results of two distributions were combined with the corresponding cut-off value. Differences between methods were quantified by simple linear regression based on the all laboratory trimmed mean. To assess the clinical consequence of method-specific differences and cut-off values, a clinical data-set of 1040 patients with an initial prostate-specific antigen measurement and concomitant conclusive prostate biopsy was retrospectively collected. Sensitivity and specificity for prostate cancer were calculated for all EQAS participants individually. Results In the Netherlands, seven different prostate-specific antigen methods are used. Interestingly, 67% of these laboratories apply age-specific cut-off values. Methods showed a maximal relative difference of 26%, which were not reflected in the cut-off values. The largest differences were caused by the type of cut-off, for example in the Roche group the cut-off value differed maximal 217%. Clinically, a fixed prostate-specific antigen cut-off has a higher sensitivity than an age-specific cut-off (mean 89% range 86–93% versus 79% range 63–95%, respectively). Conclusions This study shows that the differences in cut-off values exceed the method-specific differences. These results emphasize the need for (inter)national harmonization/standardization programmes including cut-off values to allow for laboratory-independent clinical decision-making.

Prostate-Specific Antigen Kinetics in Clinical Decision-Making During Active Surveillance for Early Prostate Cancer—A Review

2008 ◽  
Vol 54 (3) ◽  
pp. 505-516 ◽  
Author(s):  
Roderick C.N. van den Bergh ◽  
Stijn Roemeling ◽  
Monique J. Roobol ◽  
Tineke Wolters ◽  
Fritz H. Schröder ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Decision Making ◽  
Prostate Specific Antigen ◽  
Active Surveillance ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Clinical Decision ◽  
Early Prostate Cancer

Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer.

1993 ◽  
Vol 11 (4) ◽  
pp. 607-615 ◽  
Author(s):  
W K Kelly ◽  
H I Scher ◽  
M Mazumdar ◽  
V Vlamis ◽  
M Schwartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Specific Antigen ◽  
Phase Iii ◽  
Cancer Center ◽  
Hormone Refractory Prostate Cancer ◽  
Data Set ◽  
Hormone Refractory

PURPOSE To evaluate the prognostic significance of pretreatment parameters and posttherapy declines in prostate-specific antigen (PSA) in relation to the survival of patients with hormone-refractory prostate cancer. PATIENTS AND METHODS One hundred ten assessable patients treated on seven sequential protocols at Memorial Sloan-Kettering Cancer Center (MSKCC) for hormone-refractory prostate cancer were evaluated for 29 different pretherapy and posttherapy parameters, including a posttherapy decline in PSA of 50% and 80% from baseline. RESULTS In the univariate analysis, initial Karnofsky performance status (KPS) > or = 80% was associated with a favorable outcome (P = .005), while age, extent of disease on bone scan, and individual sites of metastatic disease were not significant. No difference in survival was observed between patients with measurable or assessable (bone only) disease. Initial hemoglobin (HGB; P = .0012), alkaline phosphatase (ALK; P = .0015), and lactate dehydrogenase (LDH; P = .0002) levels were significant discriminators, while the initial PSA was not. Using a landmark analysis, a significantly longer median survival rate was observed for patients with a > or = 50% decline in PSA (median not reached) versus patients with a less than 50% decline in PSA (median, 8.6 months; P = .0001). Multivariate analysis using the Cox proportional hazards model showed that a > or = 50% decline in PSA (P = .0004) and the natural log of LDH (P = .0001) were the two most significant variables predicting survival. The model was confirmed on an independent data set from the Norwegian Radium Hospital (NRH) in Oslo, Norway. CONCLUSION The results suggest that posttherapy PSA declines can be used as a surrogate end point to evaluate new agents in hormone-refractory prostate cancer. The criteria for response need prospective validation in phase III trials.

scholarly journals THE ROLE OF THE CLINICAL AND MOLECULAR ASSAYS IN PROSTATE CANCER DETECTION

2017 ◽  
Vol 10 (6) ◽  
pp. 11 ◽  
Author(s):  
Fatemeh Mansouri
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Cancer Detection ◽  
Clinical Decision Making ◽  
False Positive Rate ◽  
Specific Antigen ◽  
Clinical Decision ◽  
Therapeutic Success ◽  
Prostate Cancer Detection ◽  
Molecular Assays

To assess the correlation between the clinical and molecular assays in identify early and robust prostate cancer detection. Early detection, management of cancer and decision about the disease are important for beneficial treatment of prostate cancer. We used a computerized search of the Medline/ PubMed databases with the key words prostate cancer, biomarker, and early detection. Clinical management of cancer is facilitated by a conventional test such as prostate-specific antigen and digital rectal exam for application in clinical practice. Although these tests have significantly reduced the mortality with prostate cancer, but have some drawbacks and false positive rate. Fortunately, there are strong correlations between the clinical and molecular assays in identifying early and robust cancer detection, because molecular assays are less invasive and reliable. The use of genetic markers has the potential to providing useful prognostic or predictive information into clinically useful diagnostic tests to improve clinical decision-making and enhance therapeutic success. Different clinical and molecular assays are for detecting prostate cancer and use the biomarkers as potential tumor markers could be a useful predictor in the screening and monitoring to avoid over treatment prostate cancer.

scholarly journals Appropriate Use of Nomograms to Guide Prostate Cancer Treatment Selection

2010 ◽  
Vol 8 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Andrew K. Lee ◽  
Christopher L. Amling
Keyword(s):  
Prostate Cancer ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Clinical Decision ◽  
Ease Of Use ◽  
Due Diligence ◽  
Clinical Factors ◽  
Prostate Cancer Treatment ◽  
Large Numbers ◽  
Continuous Scale

For decades physicians have attempted to accurately predict post-treatment outcomes before performing prostate cancer interventions. Use of basic clinical factors, such as clinical T-stage, biopsy Gleason sum, and pretreatment prostate specific antigen, has allowed some level of prediction of pathologic and clinical outcomes. However, these basic tables and risk stratification schema provide a broad range of potential outcomes. The rapid growth of retrospective research in prostate cancer has yielded an abundance of additional potential prognostic factors that may influence outcomes of interest; however, incorporating and understanding the significance of these ever-expanding factors is difficult for even the most experienced physicians. Nomograms incorporate these factors (including treatment-specific) and assign them relative weights to provide a probability of the outcome of interest on a graphical scale. They distill large numbers of data into a manageable format and provide the probability of outcomes on a continuous scale rather than in categoric groups. However, because they require a computation to generate a probability, they are not amenable to memorization, which decreases ease of use. Furthermore, these numbers still have associated confidence intervals and the models are largely derived from retrospective data, which have inherent drawbacks. Clinicians and patients should still exercise due diligence when interpreting the results of these nomograms, and these prediction tools should not serve as a stand-alone substitute for clinical decision-making.

What is the role of microRNA-301A expression as a diagnostic and predictive marker of biochemical recurrence for prostate cancer?

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 19-19
Author(s):  
Adnan Dervishi ◽  
Samarpit Rai ◽  
Kristy Doan Nguyen ◽  
Thomas Michael FitzGibbon ◽  
Paul Knoll ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Predictive Marker ◽  
Clinical Decision ◽  
Definitive Treatment ◽  
Serum Samples ◽  
Prostate Hyperplasia

19 Background: Prostate specific antigen (PSA) screening for prostate cancer (PCa) remains controversial, due to its association with an increase in overdiagnosis of clinically insignificant PCa, and overtreatment. Hence, the need for more specific biomarkers to detect PCa and determine its prognosis. MicroRNA expression has previously been demonstrated as a biomarker to detect several malignancies. Studies suggest that microRNA-301a (miR-301a) inhibits the pro-apoptotic function of RUNX3, a transcription factor, and consequently activates ROCK1-mediated survival signaling in PCa. This study establishes the role of miR-301a as a reliable biomarker that can distinguish between patients with benign prostate hyperplasia (BPH) and PCa, and predict biochemical recurrence (BCR) after definitive treatment of PCa. Methods: Serum samples and tissue from prostate biopsies were collected from patients with an elevated PSA prospectively. The expression of miR- 301a was measured via reverse transcriptase-polymerase chain reaction. Additionally, miR-301a expression was retrospectively evaluated in prostatic tissue of 50 patients with PCa, including benign tissue, and correlated with clinico-pathological characteristics to predict BCR. Immunohistochemistry was performed to confirm the molecular target of miR-301a in cancerous tissue. Results: miR-301a demonstrated a significantly higher expression (p = 0.013) in both PCa tissue (Gleason 6 & 7 PCa) and serum samples (p = 0.011) when compared to BPH. Expression of miR-301a in Gleason 6 & 7 prostatectomy specimens positively correlated with patients who developed BCR when compared to patients who did not. When compared to the current nomogram for the prediction of PCa (i.e., PSA, age, race, Gleason score, and family history), incorporation of miR-301a was associated with a superior prediction of BCR at three years post-prostatectomy. Conclusions: miR-301a expression is a valuable tool for diagnosing PCa in patients with an elevated PSA. Combining miR-301a with PSA is associated with better risk stratification of PCa patients, and may help facilitate clinical decision making.

scholarly journals Clinical Utility of CLIA-Grade AR-V7 Testing in Patients With Metastatic Castration-Resistant Prostate Cancer

2017 ◽  
pp. 1-9 ◽  
Author(s):  
Mark C. Markowski ◽  
John L. Silberstein ◽  
James R. Eshleman ◽  
Mario A. Eisenberger ◽  
Jun Luo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Messenger Rna ◽  
Clinical Decision Making ◽  
Clinical Laboratory ◽  
Specific Antigen ◽  
Clinical Decision ◽  
The United States ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Purpose A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments–certified laboratory at Johns Hopkins University. Methods We contacted ordering providers of the first 150 consecutive tests by using a questionnaire-based survey to determine how the results of AR-V7 testing were used to influence clinical practice. Results In all, 142 (95%) of 150 questionnaires were completed by 38 providers from 29 sites across the United States and Canada. AR-V7 test results were reported either as CTC– (28%), CTC+/AR-V7– (30%), or CTC+/AR-V7+ (42%). Prevalence of AR-V7 detection increased with prior exposure to ATTs (abiraterone and enzalutamide naïve, 22%; after abiraterone or enzalutamide, 35%; after abiraterone and enzalutamide, 43%). Overall, management was affected by AR-V7 testing in 53% of the patients and even more often with CTC+/AR-V7+ results. AR-V7+ patients were commonly switched from ATT to taxane chemotherapy (43%) or were offered a clinical trial (43%); management remained unchanged in only 14% of these patients. Overall, patients who had a change in management on the basis of AR-V7 testing were significantly more likely to achieve a physician-reported 50% decline in prostate-specific antigen response on next-line therapy than those who did not change treatment (54% v 31%; P = .015). Conclusion Providers used AR-V7 testing to influence clinical decision making more often than not. Physicians reported that men with AR-V7+ results had the most treatment changes, and such men were preferentially managed with taxane therapy or offered a clinical trial, which may have improved outcomes.

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