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

Abstract

To determine whether the free/total prostate-specific antigen (PSA) ratio can discriminate between patients with prostate cancer or benign prostatic hyperplasia (BPH). 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. 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 < or = 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 > or = 0.15 were 71%, 76%, 38%, 93%, respectively. 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.