Algorithms based on prostate‐specific antigen (PSA), free PSA, digital rectal examination and prostate volume reduce false‐postitive PSA results in prostate cancer screening

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Abstract
Our objective was to determine whether multivariate algorithms based on serum total PSA, the free proportion of PSA, age, digital rectal examination and prostate volume can reduce the rate of false‐positive PSA results in prostate cancer screening more effectively than the proportion of free PSA alone at 95% sensitivity. A total of 1,775 consecutive 55‐ to 67‐year‐old men with a serum PSA of 4–10 μg/l in the European Randomized Study of Screening for Prostate Cancer were included. To predict the presence of cancer, multivariate algorithms were constructed using logistic regression (LR) and a multilayer perceptron neural network with Bayesian regularization (BR‐MLP). A prospective setting was simulated by dividing the data set chronologically into one set for training and validation (67%, n = 1,183) and one test set (33%, n = 592). The diagnostic models were calibrated using the training set to obtain 95% sensitivity. When applied to the test set, the LR model, the BR‐MLP model and the proportion of free PSA reached 92%, 87% and 94% sensitivity and reduced 29%, 36% and 22% of the false‐positive PSA results, respectively. At a fixed sensitivity of 95% in the test set, the LR model eliminated more false‐positive PSA results (22%) than the proportion of free PSA alone (17%) (p < 0.001), whereas the BR‐MLP model did not (19%) (p = 0.178). The area under the ROC curve was larger for the LR model (0.764, p = 0.030) and the BR‐MLP model (0.760, p = 0.049) than for the proportion of free PSA (0.718). A multivariate algorithm can be used to reduce unnecessary prostate biopsies in screening more effectively than the proportion of free PSA alone, but the algorithms will require updating when clinical practice develops with time.