COMPARISON OF PROSTATE-SPECIFIC ANTIGEN CONCENTRATION VERSUS PROSTATE-SPECIFIC ANTIGEN DENSITY IN THE EARLY DETECTION OF PROSTATE-CANCER - RECEIVER OPERATING CHARACTERISTIC CURVES

We present the results of a prospective multicenter clinical trial of nearly 5,000 men in which prostate specific antigen (PSA) density was compared to the serum PSA concentration alone for early detection of p rostate cancer. All men were evaluated with PSA and digital rectal exa mination. If PSA was elevated (greater than 4 ng./ml., Hybritech Tande m assay) or digital rectal examination was suspicious, transrectal ult rasound guided biopsies were recommended. Prostate volume was estimate d by transrectal ultrasound measurements using a prolate ellipse volum e calculation and PSA density was calculated by dividing serum PSA con centration by gland volume. Using a PSA density cutoff of 0.15 as reco mmended in the literature enhanced specificity but at the cost of miss ing half of the tumors. Of the organ confined neoplasms 47% were detec ted by a PSA of greater than 4.0 ng./ml. but they were missed by a PSA density of more than 0.15. PSA density may not be predictive for canc er because accurate estimation of transrectal ultrasound volume is dif ficult (r = 0.61 for estimated transrectal ultrasound volume versus pa thological prostate weight). However, a relationship does exist among transrectal ultrasound volume, PSA and positive predictive value for c ancer. PSA concentrations of less than 4.0 ng./ml. did not indicate a need for biopsy (positive predictive value 12 to 17%) unless the digit al rectal examination findings were suspicious for cancer. A high perc entage of patients with a PSA of more than 10 ng./ml. had cancer (30 t o 75%), regardless of gland size. Patients with intermediate PSA conce ntrations (4.1 to 9.9 ng./ml.) and a gland size of 50 cc or less had a 35 to 51% positive predictive value, while those with intermediate PS A concentrations and a large gland (more than 50 cc) had a 15% positiv e predictive value. We conclude that in men with a PSA level of 4.1 to 9.9 ng./ml., and normal digital rectal examination and transrectal ul trasound findings, the use of a PSA density cutoff of more than 0.15 f or biopsy results in half of the tumors being missed. Thus, we recomme nd that men in this group undergo biopsy based upon serum PSA concentr ation rather than PSA density.