Objectives. Nearly half of men with clinically localized prostate cancer are understaged. We evaluated whether knowledge of preoperative free prostate-specific antigen (f-PSA), complexed (c-PSA), and total (t-PSA) concentrations or the ratios thereof (f-PSA/t-PSA, c-PSA/t PSA, and f PSA/c- PSA) could improve upon the staging of prostate cancer when compared with standard PSA testing (t-PSA). In addition, we examined their associations with tumor grade and deoxyribonucleic acid (DNA) ploidy. Methods. Two hundred ninety patients with prostate cancer, 178 (61%) of whom were treated with radical prostatectomy, formed the study group. Results. Although there were significant differences in the f-PSA concentrations with respect to clinical stage, considerable overlap in PSA levels among the clinical substages was observed. Statistically significant differences but weak correlations were observed between the individual f-PSA, c-PSA, and t-PSA concentrations with regard to pathologic stage (organ-confined versus extraprostatic) and grade. No significant relationship, however, was observed with the three ratios. Higher PSA values were not always associated with a pathologic stage of pT3 or greater, and lower levels did not ensure that a tumor was organ-confined. Only a slight association was observed between c-PSA and t-PSA levels and DNA ploidy. No significant relationship was observed between the f-PSA levels as well as the three ratios with regard to DNA ploidy. A statistically significant improvement in predicting pathologic stage was observed when combining knowledge of preoperative t-PSA concentration with the c-PSA/t-PSA ratio. However, the area under the receiver operator characteristic curves was only slightly increased; as such this combination was of limited clinical utility. Conclusions. Statistically significant but weak correlations were observed between the molecular forms of PSA and stage, grade, and DNA ploidy. The significant overlap in f-PSA and c-PSA values among all stages grades, and ploidy values precluded any useful predictive information for the individual patient. As such preoperative knowledge of f-PSA and c-PSA values and the three ratios provided no additional diagnostic information over standard PSA (t-PSA) values alone.
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