Serum Free Circulating DNA Is a Useful Biomarker to Distinguish Benign versus Malignant Prostate Disease

Background: Free circulating DNA (fcDNA) has been shown to be elevated in serum of prostate cancer patients compared with benign controls. However, studies evaluating the role of fcDNA as a biomarker in a "representative" patient group who have undergone prostate cancer screening are lacking. Our study examined the use of serum fcDNA levels as a biomarker of prostate cancer in such a setting. Methods: The study included 252 men, with prostate-specific antigen (PSA) levels >4 ng/mL and/or abnormal digital rectal exam. fcDNA levels in serum before prostate biopsy were quantitated by real-time PCR amplification of the glutathione S-transferase, pi, gene. Results: Patients with PSA <= 10 ng/mL with fcDNA >180 ng/mL were at increased risk for prostate cancer compared with those with fcDNA <= 180 ng/mL (odds ratio, 4.27; 95% confidence interval, 2.05-8.88; P < 0.001; area under the curve, 0.742). The multivariate model including age, race, PSA, fcDNA, and interaction between fcDNA and PSA yielded a high negative predictive value of 93.1% and increased specificity of 33.1% compared with negative predictive value of 73.3% and specificity of 6.7% in the model excluding fcDNA. Conclusions: Our results indicate that fcDNA may improve the specificity of prostate cancer screening. Impact: Our study shows that adding fcDNA to prostate cancer screening can reduce the number of unnecessary prostate biopsies. Cancer Epidemiol Biomarkers Prev; 19(8); 1984-91. (C) 2010 AACR.