Diagnostic and Prognostic Value of cfDNA Concentration and Fragmentation in Prostate Cancer

To evaluate the value of circulating free DNA (cfDNA) in prostate cancer (PCa) by cfDNA assay and analysis of plasma and urinary cfDNA fragmentation to determine the usefulness of this parameter for risk staging and tumor progression monitoring.

A prospective, longitudinal study was conducted with 143 individuals, including a control group and a cohort of patients with PCa at different stages: localized, metastatic hormone-sensitive (mHSPC), and metastatic castration-resistant (mCRPC). Plasma and urine samples were collected to measure the concentration, fluorescence units (FU), and cfDNA fragmentation, correlating them with clinical and pathological variables.

Plasma cfDNA levels were higher in patients with PCa than in control subjects (14.3 ng/mL vs. 4.2 ng/mL, p = 0.04) and even higher in metastatic disease than in localized (20.8 ng/mL vs. 3.6 ng/mL, p < 0.001). The fragmentation size of plasma cfDNA was smaller in metastatic PCa (168.7 base pairs) than in localized PCa (172.8 base pairs, p < 0.001), suggesting that shorter fragments are associated with more aggressive disease. Following systemic treatment, the patients decreased cfDNA levels (8.3 ng/mL vs. 4.9 ng/mL, p = 0.027) and plasma FU (35.2 vs. 12.9, p < 0.001). In urine, differences were only observed in patients who progressed to CRPC than in those who remained HSPC (261.8 ng/mL vs. 43.5 ng/mL, p = 0.046).

The assay and analysis of plasma and urinary cfDNA fragmentation may provide useful biomarkers for PCa diagnosis and follow-up, particularly when differentiating between localized and metastatic disease. These findings are promising, but further research is required to determine their potential utility in clinical risk stratification and treatment monitoring.