The role of free prostate-specific antigen in the diagnosis of prostate cancer

Objective To determine whether the free/total prostate-specific antigen (PSA) ratio can discriminate between patients with prostate cancer or benign prostatic hyperplasia (BPH). Patients and methods A prospective study was conducted using free and total PSA assays in patients who underwent transrectal-ultrasound guided biopsies indicated by a total serum PSA level of >4 ng/mL and/or a positive digital rectal examination. Sixty-nine men (median age 68 years, range 57-86) who presented to our out-patient department with symptoms of prostatism were included in the study. Blood samples were drawn from all patients before biopsy. Results Histopathological examination detected prostate cancer in 17 of 69 (25%) patients and 13 of these 17 patients had a free/total PSA ratio of <0.15; only 12 of 52 (23%) patients with BPH had a ratio of <0.15. Receiver operating characteristic analysis indicated a threshold free/total PSA ratio of less than or equal to 0.15 was the optimum discriminatory level. In the whole study group, this threshold had sensitivity, specificity, positive- and negative-predictive values of 76%, 77%, 52% and 91%, respectively, There were 40 patients with serum PSA levels of 4-10 ng/mL and 17.5% (7/40) of these were diagnosed with cancer. Using a free/total PSA ratio of 0.15 would have failed to diagnose two patients of seven with prostate cancer but 30 patients would have avoided a biopsy. In this subgroup, the threshold ratio of 0.15 had sensitivity, specificity, positive- and negative-predictive values of 71%, 85%, 50% and 93%, respectively. The rates for a PSA density (PSAD) at a threshold of greater than or equal to 0.15 were 71%, 76%, 38%, 93%, respectively. Conclusion These results indicate that using the free/total PSA ratio gives a significant improvement over PSAD and total PSA values alone in the diagnosis of prostate cancer; its use may also enhance the diagnostic accuracy in patients with intermediate PSA levels.