Free circulating DNA test could improve accuracy of prostate cancer screening
MedWire News: Measuring free circulating DNA (fcDNA) levels in men undergoing prostate-specific antigen (PSA) screening for prostate cancer could improve the ability to distinguish malignant from benign disease, reports a US team.
The finding is of major clinical significance, say the researchers, who hope that the high negative predictive value of PSA-plus-fcDNA testing will be used to more accurately select which patients require biopsy.
"[Approximately] 65-70% of patients with intermediate PSA levels between 4 and 10 ng/ml are subjected to unnecessary prostate biopsies," write Rakesh Singal and colleagues from the University of Miami School of Medicine in Florida.
They estimate that by using a fcDNA cutoff point of 180 ng/ml, approximately 33% of men with a PSA level of 10 ng/ml or below will be spared biopsy.
The study included 252 men with PSA levels above 4 ng/ml and/or an abnormal digital rectal exam. The research team analyzed the men's fcDNA levels before prostate biopsy using polymerase chain reaction amplification of the glutathione S-transferase, pi gene.
Biopsy results showed that 89 men had prostate cancer, while the remaining 163 had benign disease.
fcDNA levels were higher among the cancer patients than the remaining men, at 149.4 versus 89.4 ng/ml, and based on area under the curve (AUC) analysis, a cutoff point of 180 ng/ml provided the best discrimination between cancer and benign disease.
Men with fcDNA above 180 ng/ml and a PSA of 10 ng/ml or below were 4.27 times more likely to have prostate cancer than those with the same PSA but fcDNA below 180 ng/ml.
The researchers then created multivariate analysis models adjusting for age and race, and found that the model with the best discrimination included additional adjustment for fcDNA levels above (vs below) the cut point, PSA levels of above 10 ng/ml (vs 10 ng/ml or less), and the interaction of fcDNA and PSA, giving an AUC discrimination score of 0.742.
This model also gave the highest specificity and negative predictive ability, at 33.1% and 93.1%, respectively, compared with the model excluding fcDNA, at 6.7% versus 73.3%, note Singal et al.
"Our results indicate that fcDNA levels could act as a discriminating marker in patients with PSA 10 ng/ml or less," concludes the team.
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By Sarah Guy