PCA3 sensitivity and specificity for prostate cancer detection in patients with abnormal PSA and/or suspicious digital rectal examination. First Latin American experience
Urology Department, Clinica Las Condes, Santiago, Chile. Urologic Oncology
(Impact Factor: 2.77).
06/2012; 31(8). DOI: 10.1016/j.urolonc.2012.05.002
INTRODUCTION: Prostate Cancer Gene 3 (PCA3) is a recently described and highly specific urinary marker for prostate cancer (CaP). Its introduction in clinical practice to supplement low specificity of prostate specific antigen (PSA) can improve CaP diagnosis and follow-up. However, before its introduction, it is necessary to validate the method of PCA3 detection in distinct geographic populations. OBJECTIVES: Our aim was to describe for the first time in Latin America, the application of the PROGENSA PCA3 assay for PCA3 detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate biopsy. MATERIALS AND METHODS: Sixty-four Chilean patients (mean age, 64 years) with indication of prostate biopsy because of elevated PSA and/or suspicious digital rectal examination (DRE) were prospectively recruited. PCA3 scores were assessed from urine samples obtained after DRE, before biopsy, and compared with PSA levels and biopsy outcome. RESULTS: The median PSA value and mean PCA3 score were 5.8 ng/ml and 31.7, respectively. Using a cutoff PCA3 score of 35, the sensitivity and specificity for detecting CaP were 52% and 87%, respectively. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA, for the same group of patients. In patients with previous negative biopsy, PCA3 specificity increased by 2.2%. CONCLUSIONS: This is the first report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those reported in other populations in the literature, demonstrating the reproducibility of the test. PCA3 score was highly specific and we specially recommend its use in patients with persistent elevated PSA and prior negative biopsies.
Available from: Parvez Syed
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ABSTRACT: Tumour-associated antigens (TAA) can be detected prior to clinical diagnosis and thus would be ideal biomarkers for early detection of cancer using only a few microliters of a patient's serum. In this article we provide a summary of TAA screening and serum-profiling conducted for breast, prostate, lung and colon cancers. Different methodological approaches, including SEREX, SERPA, and phage display for TAA identification and TAA panels are summarised, and a revision of array based techniques is provided. The most promising studies performed on these cancers (performed with 80-400 serum samples, including controls) obtained sensitivities in a range of 44-95% and specificities of 80-100%. From the various studies reviewed, only one performed cross validation (AUC=0.71) in a prostate cancer study. Thus, albeit receiver operation characteristics are very promising, cross validation of most studies is still missing. Additionally, the concerted action of research groups for standardization of serum-TAA testing and cross validation is required. Along with today's technological options, the chances of establishing TAA biomarkers are now higher than ever before. This may also be true for confirmation and validation of already existing data, which is a prerequisite for implementation of TAA biomarkers into clinical diagnostics. This article is part of a Special Issue entitled: Integrated omics.
Available from: Emmanuel Nna
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ABSTRACT: Many candidate biomarkers for diagnosis of prostate cancer have been investigated, but prostate-specific antigen (PSA) testing remains the frontline test for both mass screening and individual clinical testing. Although the PSA test is cost-effective, analytically reliable, and flexibly high throughput, it has a very weak correlation with prostate malignancy. This has resulted in over-diagnosis and over-treatment of patients leading to costly economic, social, and psychological impacts. PSA testing lacks the ability to molecularly characterize prostate diseases and define aggressiveness and lethality, which are necessary to influence choice of treatment. Therefore, newer molecular tests are beginning to replace the PSA tests. The prostate cancer antigen 3 test has shown superiority and is now widely used. The recently reported sarcosine urine test, the already delineated TMPRSS2: ETS fusion genes, the glutathione-S-transferase P1 serum marker, and enhancer of zeste homolog 2 biomarker may also help improve diagnosis and prognostication of prostate cancer. The analytical trend is toward a multiplex testing format using molecular and/or proteomic techniques that are reliable, accurate, reproducible, and ensure rapid quantitation. Therefore, validation of these newer biomarkers and their assays are necessary for both large-scale clinical trials and clinical utility.
Available from: Virginie Vlaeminck
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ABSTRACT: While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen's and Chun's nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun's and Hansen's nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision.
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