THE ADDITIONAL VALUE OF FREE PROSTATE-SPECIFIC ANTIGEN TO THE BATTERYOF AGE-DEPENDENT PROSTATE-SPECIFIC ANTIGEN, PROSTATE-SPECIFIC ANTIGENDENSITY AND VELOCITY

This study describes the value of using the fraction of free prostate- specific antigen as a further marker in the early detection of prostat e cancer. This newly introduced marker is compared to the usual batter y of age-dependent total prostate-specific antigen, prostate-specific antigen density (mu g/l x g tissue) and prostate-specific antigen velo city (mu g/l x year). Determination of total prostate-specific antigen and free prostate-specific antigen was performed on fresh serum sampl es obtained from 3470 symptomatic patients aged 45-80 attending the Ur ology Clinics, or their General Practitioners. Among them, 310 patient s had total prostate-specific antigen above the age-dependent cut-off, and/or free/total prostate-specific antigen under 11%, with different prostate-specific antigen densities and velocities. Only 147 patients complied to undergo biopsy: in 72 of those patients, benign prostatic disease was histologically confirmed, while in 75 patients primary pr ostate cancer was histologically confirmed. Total and free prostate-sp ecific antigen levels were determined using the third generation DPCs prostate-specific antigen assay performed on the Immulite automated im munoassay instrument. Total prostate-specific antigen age reference va lues were adopted from Oesterling et al. (J Am Med Ass 1993; 270:860-4 ); the prostate-specific antigen density was considered suspicious of prostate cancer if it was greater than 0.15 mu g/l prostate-specific a ntigen per gram tissue (Seaman et al. Urol Clin N Am 1993; 20:653); pr ostate-specific antigen velocity greater than 0.75 mu g/l x year (Cart er et al., J Am Med Ass 1992; 267:215) was considered suspicious for p rostate cancer. Of the 147 patients, 75 had prostate cancer and 72 had benign prostatic hypertrophy. The difference between prostate cancer and benign prostatic hypertrophy was significantly reflected only by f ree/total prostate-specific antigen and prostate-specific antigen velo city. These parameters also provided the best sensitivity and specific ity. Only these parameters proved to be significant when using a backw ards logistic regression model (prostate-specific antigen velocity, p = 0.007 odds ratio 2.782; free/total prostate-specific antigen %, p = 0.016 odds ratio 2.678). Combinations of various parameters became sig nificant when including free/total prostate-specific antigen, increasi ng prostate cancer detection to 88%. We conclude that free/total prost ate-specific antigen is the most significant among prostate-specific a ntigen quantities (total age-dependent prostate-specific antigen, pros tate-specific antigen density and prostate-specific antigen velocity). Adding this parameter to other prostate-specific antigen parameters i mproves the discrimination between prostate cancer and benign prostati c hypertrophy for the population at risk.