The effect of digital rectal examination, flexible cystoscopy and prostatic biopsy on free and total prostate specific antigen, and the free-to-total prostate specific antigen ration in clinical practice

Purpose: We evaluated the effects of common urological maneuvers on serum free prostate specific antigen (PSA) and established guidelines for clinical practice. Materials and Methods: Total and free PSA, and free-to-total PSA ratio were determined in 82 men with lower urinary tract symptoms before and 30 minutes after 3 different prostatic manipulations: 1) digital rectal examination (36 cases), 2) flexible cystoscopy (26) and 3) transrectal ultrasound guided prostatic biopsy (20). PSA forms were measured with Hybritech Tandem-R* assays. Results: Cystoscopy had no effect on total PSA, while digital rectal examination had a slight, statistically significantly positive effect and biopsy uniformly increased total PSA (geometric mean ratio 2.43, t = 5.08, p < 0.001). Free PSA was increased by digital rectal examination (geometric mean ratio 1.67, t = 4.25, p < 0.001), prostatic biopsy (geometric mean ratio 4.80, t = 7.48, p < 0.001) and cystoscopy (geometric mean ratio 1.21, t = 2.51, p = 0.019). There was a significant increase in free-to-total PSA ratio after each maneuver. The rate of change in free PSA and free-to-total PSA ratio after biopsy differed between patients with benign and malignant histological findings. Conclusions: Free PSA and free-to-total PSA ratios are altered by all forms of prostatic manipulation. The PSA response to manipulation may be different in patients with prostatic malignancy. Phlebotomy must precede digital rectal examination in the clinical and research setting to avoid misleading results.