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Prognostic Value of Preoperative Serum Cell-Free Circulating DNA in Men with Prostate Cancer Undergoing Radical Prostatectomy

Authors' Affiliations: The James Buchanan Brady Urological Institute, Departments of ¹ Urology, ² Oncology, ³ Pathology, and ⁴ Pharmacology, ⁵ The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and ⁶ Urologische Klinik und Poliklinik, Universitätsklinikum Großhadern, Ludwig-Maximilians-Universität München, Munich, Germany

Requests for reprints: Patrick J. Bastian, Urologische Klinik und Poliklinik, Universtätsklinikum Großhadern, Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 Munich, Germany. Phone: 49-89-7095-2971; Fax: 49-89-7095-8890; E-mail: patrick.bastian{at}gmx.de.

Purpose: We evaluated the association of preoperative serum cell-free circulating DNA concentration in men with clinically localized prostate cancer who underwent radical prostatectomy with prostate-specific antigen (PSA) recurrence.

Experimental Design: One hundred and ninety-two men with clinically localized prostate cancer, who underwent radical prostatectomy at the Johns Hopkins Hospital and had preoperative serum available for analyses constituted our study population. All serum samples were collected before prostate biopsy or at least 4 months after prostate biopsy. The total amount of serum cell-free circulating DNA from each sample was calculated using a standard curve generated via quantitative real-time PCR. PSA recurrence was defined as a single postoperative PSA level of 0.2. The natural logarithm (ln) of the DNA concentration was used for statistical analyses.

Results: Of the 192 men in our study, 56 (29%) experienced PSA recurrence within the study period (median time to PSA recurrence 2 years). The median follow-up time for men free of disease at last follow-up was 3 years. The median serum cell-free DNA concentration of all men in the study was 5.3 ng/mL (mean 18.05 ng/mL; range 0.2-320 ng/mL). The mean serum DNA concentration for men who recurred and for those who did not was 3.8 ± 34.1 and 13.7 ± 33.6 ng/mL, respectively (P = 0.001). In a univariate analysis, ln DNA concentration was significantly associated with PSA recurrence (hazard ratio, 1.49; 95% confidence interval, 1.3-1.8; P < 0.001). In the multivariate model, ln DNA concentration was significantly associated with PSA recurrence (hazard ratio, 2.56; 95% confidence interval, 1.1-1.6; P = 0.003). Using bootstrap analyses, serum cell-free DNA concentrations 5.75 ng/mL were associated with an increased risk of PSA recurrence within 2 years of radical prostatectomy.

Conclusion: Our study suggests that preoperative serum cell-free DNA concentration may be a useful prognostic biomarker for men with clinically localized prostate cancer treated with radical prostatectomy.

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