0.75 ng/mL per year are suggestive of cancer. For a 50-year-old male, an increase from 2.5 to 3.9 ng/mL in a I-year period would warrant fuher testing, even though the level is still in the "normal" range. Free and complexed PSA measurements are used to determine which men require a biopsy when the PSA level is in the range of 4 to 10 ng/mL. In cancer, the level of free PSA is lower. Using a 25% threshold of free PSA for patients with levels in the range of 4 to 10 ng/mL, specificity was improved by 20% while maintaining a sensitivity of95%. Fuher refinements to increase the specificity of distinguishing benign and malignant conditions involve the determination of the ratios of free to total, complexed to total, and free to complexed PSA. Using normal ranges for free/total PSA of>O .15, for complexed total PSA of 0.25 improved specificity in one study by 20%. These modifications are designed to reduce the frequency of biopsies in men without cancer.">