STRATFORD, Connecticut--Several studies have shown the ability of the
percent-free PSA blood test to help differentiate benign prostatic
hyperplasia (BPH) from prostate cancer among men with elevated PSA
levels and thus reduce the need for prostate biopsy. Now, two studies
in the September issue of Urology have further defined the
situations in which percent-free PSA may be used to improve the
performance of total PSA level results.
Alan W. Partin, MD, PhD, of Johns Hopkins School of Medicine, and his
colleagues at Dianon Systems Inc., analyzed percent-free PSA levels
in a database, provided by Dianon, of nearly 4,000 men with
moderately elevated PSA levels (4.0 to 20 ng/mL) diagnosed as either
cancer or BPH. (Dianon has developed an investigational
double-antibody radio-immunometric assay for measuring percent-free PSA.)
They found that patient age and total PSA levels were the most
effective independent variables when interpreting percent-free PSA.
The researchers then developed a statistical algorithm combining age,
total PSA, and percent-free PSA to calculate the probability of
prostate cancer. They tested the model in an additional dataset of
525 patients to determine its clinical utility at selected
The validation study showed that an 18% probability cutoff detected
95% of malignant biopsies and 34% of negative biopsies. "A 25%
free PSA cutoff would have detected 95% of malignant cases and
eliminated 23% of benign cases; that is, 23% of the benign cases had
higher than 25% free PSA," Dr. Partin said. Further, the
algorithm proved more effective than percent-free PSA alone in
differentiating BPH from prostate cancer. It yielded an 11%
percentage point increase in specificity over percent-free PSA alone
(34% vs 23%), he said.
"These predicted probabilities can be used in the context of the
patients risk tolerance and preference for decision making
regarding the need for prostate biopsy," he concluded.
The second study was designed to determine an appropriate lower limit
for total PSA value at which percent-free PSA distributions would
differ between benign and malignant cases and for which percent-free
PSA could be used to predict prostate cancer.
Lower Limit of Total PSA
The researchers examined the performance of percent-free PSA in 479
men with low PSA values (4.0 ng/mL or less) who had undergone
diagnostic prostate biopsy. The study is the largest of its kind of
men with total PSA levels of 4.0 ng/mL or less.
Stacy J. Childs, MD, of the University of Colorado Health Sciences
Center, found that percent-free PSA was not an indicator of prostate
cancer until total PSA reached 4.0 ng/mL. When total PSA was at least
3.9 ng/mL, the percent-free PSA distributions for benign and
malignant cases were significantly different. However, at the 3.9
ng/mL level, percent-free PSA testing could not predict prostate cancer.
Based on their evaluation, the investigators concluded that
percent-free PSA measurements should be applied only to men with
total PSA values of 4.0 ng/mL or higher.
"Further studies are necessary to confirm these findings and
evaluate whether differences in assay methodology affect
results," they said.
Coauthors for both Dr. Partin and Dr. Childs were Grant D. Carlson
and Christina B. Calvanese of Dianon Systems (Urology
52:450-454; 455-461, 1998).