title: Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancer.
abstract: OBJECTIVE
  To investigate whether preoperative plasma levels of free DNA can discriminate between men with localized prostate cancer and benign prostatic hyperplasia (BPH).
  
  
  METHODS
  In all, 161 referred patients suspicious for prostate cancer either by an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) were included in this prospective study. Peripheral plasma was taken before prostate biopsy and genomic DNA was extracted from the plasma using the a commercial kit and a vacuum chamber. After controlling for age, PSA level, the percentage free/total (f/t) PSA and prostate volume, the median prostate cancer plasma DNA concentration served as diagnostic threshold in uni- and multivariate logistic regression models. Multivariate models were subjected to 200 bootstraps for internal validation and to reduce over-fit bias.
  
  
  RESULTS
  Subgroups consisted of 142 men with clinically localized prostate cancer and 19 with BPH. The median plasma concentration of cell-free DNA was 267 ng/mL in men with BPH vs 709 ng/mL in men with prostate cancer. In univariate analyses, plasma DNA concentration was a statistically significant and informative predictor (P = 0.032 and predictive accuracy 0.643). In multivariate analyses, it remained statistically significant after controlling for age, tPSA, f/tPSA and prostate volume, increasing the predictive accuracy by 5.6%.
  
  
  CONCLUSIONS
  Our data suggest that plasma DNA level is a highly accurate and informative predictor in uni- and multivariate models for the presence of prostate cancer on needle biopsy. The predictive accuracy was substantially increased by adding plasma DNA level. However, larger-scale studies are needed to further confirm its clinical impact on prostate cancer detection.
authors.affiliation: Department of Urology, University Hospital Hamburg Epppendorf, Hamburg, Germany.
authors.forename: Felix K-H
authors.initials: FK
authors.lastname: Chun
authors.forename: Imke
authors.initials: I
authors.lastname: Müller
authors.forename: Imke
authors.initials: I
authors.lastname: Lange
authors.forename: Martin G
authors.initials: MG
authors.lastname: Friedrich
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.forename: Heidi
authors.initials: H
authors.lastname: Schwarzenbach
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D004273:DNA, Neoplasm / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000175:diagnosis*; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D017430:Prostate-Specific Antigen