Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancer.
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.
Chun
Felix K-H
FK
Department of Urology, University Hospital Hamburg Epppendorf, Hamburg, Germany.
Müller
Imke
I
Lange
Imke
I
Friedrich
Martin G
MG
Erbersdobler
Andreas
A
Karakiewicz
Pierre I
PI
Graefen
Markus
M
Pantel
Klaus
K
Huland
Hartwig
H
Schwarzenbach
Heidi
H
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
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D017430:Prostate-Specific Antigen