Clinical usefulness of free PSA in early detection of prostate cancer

Objective: Measurement of serum prostate-specific antigen (PSA) is widely u sed as an aid in early detection of prostate cancer. Most patients with pro state cancer and a PSA level less than 10.0 ng/ml have early-stage disease. Thus, the detection of prostate cancer in its potentially curable stages r equires the use of low PSA cutoffs, inevitably leading to many unnecessary biopsies. The combined use of free PSA and total PSA increases specificity of early detection. To develop risk assessment guidelines and a cutoff Valu e of ratio of free (f) to total (t) PSA with a high predictive Value for pr ostate cancer in men to whom the test would be applied in real life practic e, a multicenter early detection trial was initiated. Patients and Methods: In one week in November 1997, 963 urologists prospectively examined 11,644 men between 45 and 75 years by digital rectal examination (DRE) and prosta te-specific antigen with 4.0 ng/ml as cutoff. Data of physical examination were collected by questionnaire. At this time participants were not aware o f their PSA values. Suspicious findings were further investigated with sext ant biopsy. Prostate volume was determined with transrectal ultrasound (TRU S). Different cutoff levels were correlated to age and detection rate. Resu lts: From 1,115 biopsied men, the data of 633 men fulfilled the criteria DR E-negative, TRUS-estimated volume, and PSA 4.0-10.0 ng/ml. In that cohort 9 1 cancers were detected. Percentage of fPSA was significantly more predicti ve of cancer than tPSA (p < 0.001). The area under the ROC curve was 0.72 f or percent fPSA (% fPSA) and 0.62 for total PSA. The cancer risk nearly dou bled using a cutoff of 10% fPSA, the median %PSA level of the detected canc ers. A better discrimination of cancer and noncancer especially in the age group above 70 years is possible. Using a cutoff of 16% fPSA increases posi tive predictive value (PPV) to 25% missing only 4% of cancers. Nearly 45% o f the biopsies could be avoided. In the age group 45-69 years, a cutoff of 20% fPSA leads to PPV of 15%, missing 6% of cancers. Unnecessary biopsies c ould be avoided in 12%. Conclusions: Using %fPSA in early detection of pros tate cancer reduces the number of unnecessary biopsies, especially in men w ith negative rectal examination in the PSA range of 4.0-10.0 ng/ml. In orde r to diminish biopsy rate in men 70 years or older a cutoff of 16% fPSA sho uld be used. A cutoff of 20% fPSA in men younger than 70 years is recommend ed to increase sensitivity in that age group.