Clinical value of longitudinal free-to-total prostate specific antigen ratio slope to diagnosis of prostate cancer.

Abstract

Free and total serum prostate specific antigen (PSA) levels are frequently used for early prostate cancer detection in men with a total PSA in the 2.6 to 10 ng/ml range. Results from a longitudinal study suggested that the free-to-total PSA ratio (F/T PSA), declining the decade before prostate cancer diagnosis, is the earliest serum marker predicting a subsequent diagnosis of prostate cancer. Other than this study, there are limited data on the predictive value of longitudinal F/T PSA measurements for subsequent cancer. To evaluate the clinical importance of a decreasing F/T PSA, we compared longitudinal F/T PSA in volunteers in a prostate cancer screening study. We evaluated 657 volunteers in a screening study with a total PSA of 2.6 to 10 ng/ml but whose initial biopsies were either negative for cancer or were waived. To obtain meaningful F/T PSA slopes, the patients have been followed with at least 3 F/T PSA levels measured for 3 or greater years (mean 3.5, median 3.5, range 3 to 5.3). Of these men 22 subsequently were diagnosed with prostate cancer. We calculated the F/T PSA slope as the last F/T PSA minus the first F/T PSA divided by the interval between the measurements. The F/T PSA slopes of the patients with and without cancer were compared using chi-square analysis. Mean F/T PSA slope for the patients with cancer was -0.06 (median -0.03, range -0.63 to 0.22) compared to mean slope of -0.02 (median -0.01, range -0.57 to 0.69) for patients without cancer (p = 0.21). Of the patients with cancer 61% had a negative slope compared with 54% of patients without cancer (p = 0.59). The positive predictive value of a negative F/T PSA slope for subsequent cancer detection to date is only 4%. A decreasing F/T PSA during a 3 to 5-year interval has little value in predicting subsequent diagnosis of prostate cancer. Further followup of a larger number of patients will be required to determine the value of longitudinal F/T PSA measurements in early prostate cancer detection.