The utility of free to total PSA ratio for detecting prostate cancer in Japanese men with total PSA between 2.1 and 10 ng/ml

We sought to determine whether the free to total prostate specific antigen (PSA) ratio in men with "gray zone" total PSA could accurately indicate the presence or absence of cancer, thus reducing the number of unnecessary biopsies without lessening the chance of detecting early stage prostate cancers. In 137 patients with total PSA levels between 2.1 and 10.0 ng/ml, we examined total PSA, free to total PSA ratio, PSA density (PSAD), and prostatic volume measured by transrectal ultrasound, and used these features to predict histologic features determined following sextant biopsy and/or surgery of the prostate. Of 137 patients with intermediate PSA levels, 25 (18%) had cancer. With a free to total PSA cut-off of 20%, cancer would not have been detected in 4 of the 25 patients (84% sensitivity), and 36% of the unnecessary negative biopsies would have been successfully avoided (p < 0.0005). With a PSAD cut-off of 0.15, cancer would have been missed in 4 of the 25 patients (84% sensitivity) and a 50% reduction in unnecessary negative biopsies would have been possible (p < 0.0005). Of 41 patients with large prostatic glands (>40 cm(3)), cancer was detected in only one, compared with 24 (25%) of 96 patients with small glands (<40 cm(3)) (p = 0.002). The results of receiver operating characteristic analysis indicated that PSAD, free to total PSA ratio, and prostatic volume would be effectively applicable to the diagnosis of cancer (areas under the curve: 0.7562, 0.7564, and 0.7693, respectively). At 100% sensitivity, specificity was highest for PSAD used in conjunction with ratio of free to total PSA. All patients with cancer had PSAD > 0.15 and/or free to total PSA < 15%. Patients with PSAD < 0.15 and free to total PSA ratio > 15% had no cancer (p < 0.0001). By this procedure, a 48% (54 of 112) reduction in the number of unnecessary biopsies would have been possible. Use of the free to total PSA ratio, measured with the AxSYM system, can significantly reduce unnecessary negative biopsies in patients with intermediate levels of PSA. Prostatic volume data can enhance the usefulness of this ratio for diagnosing prostate cancer.