Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer

Purpose: Determining serum total prostate specific antigen (PSA) has proved to be a valuable diagnostic aid for detecting prostatic carcinoma, althoug h the lack of specificity has limited its usefulness. Studies indicate that the use of percent free PSA would improve specificity while maintaining se nsitivity. Since complexed PSA represents the major proportion of measurabl e PSA in serum, we determined whether it represents a single test alternati ve to the use of percent free PSA for the early detection of prostate cance r. Materials and Methods: Archival serum was obtained from 385 men with no evi dence of malignancy on biopsy and 272 with biopsy confirmed prostate cancer . We determined the concentration and proportion of total, complexed and fr ee PSA. Results: Receiver operating characteristics analysis using total PSA result s from all samples (range 0.32 to 117 ng./ml.) indicated that the areas und er the curve for complexed PSA alone as well as the free-to-total and compl exed-to-total PSA ratios were similar and significantly greater than those for total PSA alone. Within the range of 85% to 95% sensitivity receiver op erating characteristics analysis revealed that the specificity of complexed PSA was higher than that of total PSA and equivalent to that of the free-t o-total PSA ratio. We noted a similar improvement in specificity in the 4 t o 10 ng./ml. total PSA range. Using published cutoff values for complexed, total and percent free PSA when total PSA was in the 4 to 10 ng./ml. range the sensitivity and specificity of complexed and percent free PSA were simi lar. Within the 4 to 10 ng./ml, total PSA range the population of patients with no evidence of malignancy and complexed PSA below the upper limit was different with respect to total PSA from that with no evidence of malignanc y and free PSA greater than 25%. Conclusions: The measurement of complexed PSA represents an alternative to the use of percent free PSA, although the patient populations identified by the 2 tests are different.