Free-to-total prostate-specific antigen (PSA) ratio improves the specificity for detecting prostate cancer in patients with prostatism and intermediate PSA levels

To investigate the clinical significance of the free-to-total prostate-specific antigen (PSA) ratio in improving the specificity of PSA measurement for detecting prostate cancer within the diagnostic intermediate range (4-10 ng/mL total PSA) in patients referred for the treatment of urinary symptoms.

Serum samples were obtained from 333 consecutive patients with obstructive and irritative urinary symptoms. Of these men, 114 had total PSA levels of 4-10 ng/mL; 22 had prostate cancer (group 1) and 71 had benign prostatic hyperplasia (BPH, group 2). Group 3 consisted of 21 patients with BPH and a chronic indwelling catheter. The concentrations of free and total PSA (ProStatus, Wallac Oy, Turku, Finland) and PSA complexed to alpha-1-antichymotrypsin were measured and the free-to-total PSA ratio calculated. All patients under 70 years of age or with suspicious findings on digital rectal examination or transrectal ultrasonography underwent ultrasound-guided sextant prostate biopsies. Of the 114 patients, 105 (92%) underwent transurethral resection of the prostate and six (5%) radical retropubic prostatectomy.

Patients in group 1 had significantly lower median free PSA concentrations (0.78 ng/mL vs 1.13 ng/mL, P < 0.001) and a lower free-to-total PSA ratio (12.1% vs 19.9%, P < 0.001) than those in group 2. The differences were similar between group 1 and group 3 (median free PSA in group 3, 1.06 ng/mL, P = 0.03, and free-to-total PSA ratio 18.7%, P = 0.007). There were no significant differences between patients in groups 2 and 3. The free-to-total PSA ratio had a higher specificity than total PSA at all sensitivity levels, e.g. a threshold free-to-total PSA ratio of 0.20 detected 91% of cancers and spared 48% (group 2) or 46% (group 3) from unnecessary biopsies. The area under the receiver operating characteristic curve for group 1 vs group 2 was 0.56 (total PSA) and 0.78 (free-to-total PSA ratio) and for group 1 vs group 3 was 0.56 (total PSA) and 0.81 (free-to-total PSA ratio).

In those patients with extensive symptoms from BPH and requiring surgical treatment, the free-to-total PSA ratio improves the specificity for detecting prostate cancer in the diagnostic 'grey zone' of 4-10 ng/mL total PSA. This improvement occurred in patients with or without a chronic indwelling catheter for urinary retention.