Prospective Evaluation of Operating Characteristics of Prostate Cancer Detection Biomarkers

PurposeWe assessed the independent predictive values of the serum markers free prostate specific antigen, proenzyme prostate specific antigen, neuroendocrine marker and Dickkopf-1 compared to serum prostate specific antigen and other standard risk factors for early prostate cancer detection.Materials and MethodsFrom the prospectively collected SABOR cohort 250 prostate cancer cases, and 250 mean age matched and proportion of African-American race/ethnicity matched controls were selected who had a prior available prostate specific antigen and digital rectal examination. Serum samples were obtained, and free prostate specific antigen, [-2]proenzyme prostate specific antigen, Dickkopf-1 and neuroendocrine marker were measured. AUC, sensitivities and specificities were calculated, and multivariable logistic regression was used to assess the independent predictive value compared to prostate specific antigen, digital rectal examination, family history, prior biopsy history, race/ethnicity and age.ResultsThe AUCs (95% CI) were 0.76 (0.71, 0.8) for free prostate specific antigen, 0.72 (0.67, 0.76) for [-2]proenzyme prostate specific antigen, 0.76 (0.72, 0.8) for %free prostate specific antigen, 0.61 (0.56, 0.66) for %[-2]proenzyme prostate specific antigen, 0.73 (0.68, 0.77) for prostate health index, 0.53 (0.48, 0.58) for Dickkopf-1 and 0.53 (0.48, 0.59) for neuroendocrine marker. In the 2 to 10 ng/ml prostate specific antigen range the AUCs (95% CI) were 0.58 (0.49, 0.67) for free prostate specific antigen, 0.53 (0.44, 0.62) for [-2]proenzyme prostate specific antigen, 0.67 (0.59, 0.75) for %free prostate specific antigen, 0.57 (0.49, 0.65) for %[-2]proenzyme prostate specific antigen and 0.59 (0.51, 0.67) for phi. Only %free prostate specific antigen retained independent predictive value compared to the traditional risk factors.ConclusionsFree prostate specific antigen retained independent diagnostic usefulness for prostate cancers detected through prostate specific antigen and digital rectal examination screening. Prostate specific antigen isoforms are highly correlated with prostate specific antigen. Future research is needed to identify new markers associated with prostate cancer through different mechanisms.