Serial prostate specific antigen, free-to-total prostate specific antigen ratio and complexed prostate specific antigen for the diagnosis of prostate cancer

Purpose: The free-to-total prostate specific antigen (PSA) ratio and complexed PSA have been introduced as adjuncts to total PSA for prostate cancer screening. Little data exist on the use of these tests for serial PSA screening. We compared serial total PSA, the free-to-total PSA ratio and calculated complexed PSA in men diagnosed with prostate cancer and matched controls in a population based study. Materials and Methods: We identified 90 men diagnosed with prostate cancer between 1988 and 1996 with at least 3 serial serum samples obtained at 2-year intervals who were participants in the P-Carotene and Retinol Efficacy Trial for the prevention of lung cancer. Samples were available up to 10 years before diagnosis. A total of 90 age matched men from the same cohort without prostate carcinoma were identified as controls. Free and total PSA was measured by the Abbott AxSYM dagger system. Results: Baseline demographics of cases and controls were similar. At baseline and diagnosis the men with prostate cancer had higher total and complexed PSA, and a lower free-to-total PSA ratio than controls. Mean followup was 5.2 years in cases and 5.5 in controls. The yearly change in PSA parameters in cases versus controls was 20.7% versus 3.5% for total, -3.4% versus 0.2% for free-to-total and 21.5% versus 3.4% for complexed PSA (p <0.0001). At diagnosis PSA alone was estimated to perform with more than 90% specificity in our model. Conclusions: In this population based study total PSA was superior to the free-to-total PSA ratio for predicting the development of prostate cancer. While serial changes in free-to-total PSA ratios with time were statistically significantly different in men diagnosed with prostate cancer and controls, the magnitude of these serial changes were slight enough to render them clinically insignificant.