MEASUREMENT OF THE PROPORTION OF FREE TO TOTAL PROSTATE-SPECIFIC ANTIGEN IMPROVES DIAGNOSTIC PERFORMANCE OF PROSTATE-SPECIFIC ANTIGEN IN THE DIAGNOSTIC GRAY ZONE OF TOTAL PROSTATE-SPECIFIC ANTIGEN

Objectives This study examined the clinical significance of non-comple xed (free) prostate-specific antigen (PSA) in the differential diagnos is of prostate cancer with an emphasis on patients with total PSA valu es between 4.0 and 10.0 ng/mL (the diagnostic gray zone). Methods. Ser um samples were obtained from three specimen banks, Patient samples co nsisted of 55 untreated histologically confirmed primary cancer, 62 me n with untreated benign prostatic disease histologically confirmed by 6 negative sextant biopsies, and 64 asymptomatic healthy male controls with normal digital rectal examinations and PSA values less than 4.0 ng/mL. All patients were between the ages of 50 and 75 years. Total PS A levels were determined using the PA immunoassay performed on the TOS OH AIA-1200 automated immunoassay instrument. Free PSA levels were det ermined using a monoclonal-polyclonal antibody sandwich radioimmunoass ay. The proportion of free to total PSA was calculated by dividing the patient's free PSA value by the total PSA value. Results. When all su bjects were included, both total PSA and the proportion of free to tot al PSA significantly differentiated between patients with prostate can cer and patients with benign histologic conditions (P < 0.0001). Howev er, in men with total PSA values between 4.0 and 10.0 ng/mL, the propo rtion of free to total PSA significantly differentiated between patien ts with benign and malignant histologic conditions (P = 0.0004), where as the total PSA did not (P = 0.13). Among this subgroup of patients, the analysis of sensitivity and specificity showed that the proportion of flee to total PSA had a clearly higher specificity compared with t hat of the total PSA at the same level of sensitivity. Conclusions. Me asurement of the free PSA level in a patient's serum and calculation o f the proportion of free to total PSA enhances the ability to distingu ish benign histologic conditions from cancer while retaining high sens itivity for detecting cancer in men who present with total PSA levels between 4.0 and 10.0 ng/mL. A large-scale population-based study is cu rrently in progress to confirm this preliminary finding.