Utility of Free/Total Prostate Specific Antigen (f/t PSA) Ratio in Diagnosis of Prostate Carcinoma

The discovery that PSA exists in serum in both free and complexed forms led to development of immunoassays specific for different PSA forms. This helped in measuring free PSA in the presence of PSA-ACT (PSA-alpha antichymotrypsin), hence it was possible to calculate the percent free PSA or free to total PSA ratio, measurement of which was helpful in reducing the number of unnecessary biopsies significantly, while maintaining a high clinical sensitivity for detection of cancer. The study was performed on 103 consecutive male patients (mean age 68 +/- 10.8 years SD) comprising of 90 patients with benign disease (87%) and 13 prostate carcinoma patients (13%), who had histologically proven prostate cancer. Patients with total PSA between 2-25 ng/ml were included in the study. 30 normal healthy males with age 58 +/- 10 years, served as control. Serum total PSA and free PSA were analyzed using streptavidin biotin EIA method (M/s Roche Diagnostics, Germany). The mean total PSA in normal healthy control subjects was 1.86 +/- 1.07 ng/ml. It was increased significantly in diseased condition. Its mean concentration in carcinoma patients was 12.6 +/- 5.3 ng/ml and in benign patients it was 6.3 +/- 4.6 ng/ml. The free to total PSA ratio in all the three groups was significantly different (p < 0.004) from each other. In carcinoma patients, mean f/t PSA ratio was 0.12 +/- 0.06 as compared to 0.21 +/- 0.11 and 0.28 +/- 0.17 in benign patients and in control respectively. The sensitivity and specificity of the test was calculated at different f/t PSA ratio cutoff. At 0.1 cutoff value, sensitivity of the test was 54% and specificity was 83%. The positive predictive value (ppv) was 32% and negative predictive value (npv) was 92%. From cutoff value of 0.12 to 0.16, sensitivity was increased from 54% to 85% but specificity was reduced from 78% to 67%. The ppv did not show much change and npv was increased from 92% to 97%. Increasing the cut off value thereafter showed no change in sensitivity but specificity was further reduced to 40%, therefore in this patient series, f/t PSA ratio cutoff of 0.16 was found to be the appropriate cutoff value. Combination of this ratio cutoff with other parameters like serum total PSA, DRE and TRUS helped in increasing the sensitivity of the test and this also helped in reducing the number of unnecessary biopsies. In 103 men who were biopsied, 13 (12.6%) prostatic carcinoma were identified. Among these 13 cancer patients, 9 patients had abnormal findings in DRE.7 individuals out of these 9, also had free to total PSA ratio lower than 0.16 and would have been biopsied and diagnosed anyway. If we use only f/t PSA ratio less than 0.16, to decide whom to biopsy, we would have biopsied and diagnosed 11/13 cases i.e. sensitivity of 85% but If we decide to biopsy those patients who had abnormal DRE and those who had low f/t PSA ratio, we could identify 13/13 carcinoma i.e. 100% sensitivity. Combining the f/t PSA ratio with total PSA, DRE and TRUS findings could help in reducing the number of unnecessary biopsies. 37 patients who were negative for malignancy having total PSA in the range of 5-20 ng/ml, normal DRE and TRUS findings, have been biopsied but with combination of total PSA in the range of 5-20 ng/ml, normal findings in digital rectal examination and TRUS and f/t PSA ratio more than 0.16 (cutoff), we could have avoided 16 biopsies which were unnecessary that means there was 43% reduction in unnecessary biopsies.