Prostate-specific antigen testing accuracy in community practice

BACKGROUND: Most data on prostate-specific antigen (PSA) testing come from urologic cohorts comprised of volunteers for screening programs. We evaluated the diagnostic accuracy of PSA testing for detecting prostate cancer in community practice. METHODS: PSA testing results were compared with a reference standard of prostate biopsy. Subjects were 2,620 men 40 years and older undergoing (PSA) testing and biopsy from 1/1/95 through 12/31/98 in the Albuquerque, New Mexico metropolitan area. Diagnostic measures included the area under the receiver-operating characteristic curve, sensitivity, specificity, and likelihood ratios. RESULTS: Cancer was detected in 930 subjects (35%). The area under the ROC curve was 0.67 and the PSA cutpoint of 4 ng/ml had a sensitivity of 86% and a specificity of 33%. The likelihood ratio for a positive test (LR+) was 1.28 and 0.42 for a negative test (LR-). PSA testing was most sensitive (90%) but least specific (27%) in older men. Age-specific reference ranges improved specificity in older men (49%) but decreased sensitivity (70%), with an LR+ of 1.38. Lowering the PSA cutpoint to 2 ng/ml resulted in a sensitivity of 95%, a specificity of 20%, and an LR+ of 1.19. CONCLUSIONS: PSA testing had fair discriminating power for detecting prostate cancer in community practice. The PSA cutpoint of 4 ng/ml was sensitive but relatively non-specific and associated likelihood ratios only moderately revised probabilities for cancer. Using age-specific reference ranges and a PSA cutpoint below 4 ng/ml improved test specificity and sensitivity, respectively, but did not improve the overall accuracy of PSA testing

PCA3 molecular urine assay for prostate cancer: association with pathologic features and impact of collection protocols

IntroductionPCA3 is a non-coding mRNA molecule that is overexpressed in prostate cancer. The purpose of this study is to evaluate the utility of the PCA3 molecular urine test scores to predict adverse pathologic features and catheterized specimen collection.MethodsHundred men with clinically localized prostate cancer scheduled to undergo robotic prostatectomy were enrolled in the study following a standard consent process. The study protocol consisted of providing four urine samples. Voided urine obtained following digital rectal examination (DRE) pre-operatively (Vl), catheterized urine without DRE (V2), and l0-day and 6-week postoperative voided (V3 and V4) urine samples were collected and analyzed. These four urine specimens underwent target capture, transcription-mediated amplification, and hybridization in order to quantify both PCA3 and PSA mRNA. The PCA3 score was calculated as the ratio of PCA3 to PSA.ResultsInformative rates (sufficient mRNA for analysis) for VI, V2, V3 and V4 were 91, 85, 0 and 2%, respectively. There was no significant associations with pathological stage, Gleason score >6. Higher PCA3 scores at V1 correlated with increased risk for perineural invasion (P = 0.0479).ConclusionsInformative PCA3 scores can be obtained from post-DRE voided urine as well as catheterized urine without a DRE. The PCA3 test does not seem to predict adverse pathologic features, though, may have an association with perineural invasion. The ability of PCA3 score to predict clinical outcome remains to be determined

Urinary volatile organic compounds for the detection of prostate cancer

© 2015 Khalid et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The aim of this work was to investigate volatile organic compounds (VOCs) emanating from urine samples to determine whether they can be used to classify samples into those from prostate cancer and non-cancer groups. Participants were men referred for a trans-rectal ultrasound-guided prostate biopsy because of an elevated prostate specific antigen (PSA) level or abnormal findings on digital rectal examination. Urine samples were collected from patients with prostate cancer (n = 59) and cancer-free controls (n = 43), on the day of their biopsy, prior to their procedure. VOCs from the headspace of basified urine samples were extracted using solid-phase micro-extraction and analysed by gas chromatography/mass spectrometry. Classifiers were developed using Random Forest (RF) and Linear Discriminant Analysis (LDA) classification techniques. PSA alone had an accuracy of 62-64% in these samples. A model based on 4 VOCs, 2,6-dimethyl-7-octen-2-ol, pentanal, 3-octanone, and 2-octanone, was marginally more accurate 63-65%. When combined, PSA level and these four VOCs had mean accuracies of 74% and 65%, using RF and LDA, respectively. With repeated double cross-validation, the mean accuracies fell to 71% and 65%, using RF and LDA, respectively. Results from VOC profiling of urine headspace are encouraging and suggest that there are other metabolomic avenues worth exploring which could help improve the stratification of men at risk of prostate cancer. This study also adds to our knowledge on the profile of compounds found in basified urine, from controls and cancer patients, which is useful information for future studies comparing the urine from patients with other disease states

A Simple & Convenient Solid Phase Synthesis of Bacterial Origin Octapeptide Sequence, Glu-Asp-Gly-Asn-Lys-Pro-Gly-Lys-OH

The repeating octapeptide sequence, Glu-Asp-Gly-Asn-Lys-Pro-Gly-Lys-OH derived from the glycoprotein found in Staphylococcus aureus cell wall is assembled by simple solid phase peptide synthesis methodology using a base labile linker

Clinical relevance of genetic instability in prostatic cells obtained by prostatic massage in early prostate cancer

We investigated whether genetic lesions such as loss of heterozygosity (LOH) are detected in prostatic cells obtained by prostatic massage during early diagnosis of prostate cancer (CaP) and discussed their clinical relevance. Blood and first urine voided after prostatic massage were collected in 99 patients with total prostate-specific antigen (PSA) between 4 and 10 ng ml−1, prior to prostate biopsies. Presence of prostatic cells was confirmed by quantitative RT–PCR analysis of PSA mRNA. Genomic DNA was analysed for LOH on six chromosomal regions. One or more allelic deletions were found in prostatic fluid from 57 patients analysed, of whom 33 (58%) had CaP. Sensitivity and specificity of LOH detection and PSA free to total ratio <15% for positive biopsy were respectively 86.7 and 44% (P=0.002) for LOH, and 55 and 74% (P=0.006) for PSA ratio <15%. Analysis of LOH obtained from prostatic tumours revealed similar patterns compared to prostatic fluid cells in 86% of cases, confirming its accuracy. The presence of LOH of urinary prostatic cells obtained after prostatic massage is significantly associated with CaP on biopsy and may potentially help to identify a set of patients who are candidates for further prostate biopsies

Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer

Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status