NEW ORLEANS--For prostate cancer detection, the proportion of free PSA
to total PSA, using a cut-off point of 25%, is more sensitive and specific
than total PSA and avoids many unnecessary biopsies, according to a multicenter
study presented at the American Urological Association (AUA) annual meeting.
Free PSA is a "nicked version" of the prostate-specific antigen
that floats freely in the blood. The free-to-total PSA ratio is known as
percent free PSA.
William Catalona, MD, professor and chief of urology at Washington University
School of Medicine, said that the 25% cut-off for free PSA allows about
95% of cancers to be detected and eliminates, on average, 20% of unnecessary
biopsies, largely in older men.
"This test provides useful information, particularly about men
who are in the 'gray zone,' with PSA levels between 4 and 10 ng/mL,"
Dr. Catalona said. "The problem has been that when you biopsy men
with PSAs of 4 ng/mL, only one third will actually have cancer. But if
the patient's free PSA is less than 25%, you know he has a much greater
chance of having cancer."
The study involved 773 men screened for prostate cancer who had a normal
DRE but total PSA levels of 4 to 10 ng/mL. Among the men who were diagnosed
with cancer, 95% had free PSA levels below 25%; therefore, the 25% cut-point
was determined to be reasonable for screening men with elevated total PSA.
The implications of a free PSA level actually depend somewhat on the
patient's age, prostate size, and total PSA. If two men, aged 65 and 75,
have identical free PSA readings, the older man is slightly more likely
to have prostate cancer. If two men of the same age have identical free
PSA readings, the man with the smaller prostate is more likely to have
prostate cancer, Dr. Catalona said.
"But we wanted to avoid using many different cutoffs and to develop
a test that was practical, so we settled on the single cutoff point of
25%," he said.
The study was sponsored by Hybritech, which is seeking FDA approval
to use the free PSA test diagnostically. But most companies that market
total PSA tests are already providing the free PSA component to physicians;
therefore, it can be put to use now, Dr. Catalona said. He emphasized that
the 25% cut-off is good for the Hybritech version, but may not be applicable
to other assays.
Free PSA is also predictive of tumor aggressiveness, with very low percentages
of free PSA associated with high-grade tumors, Dr. Catalona said.
For example, in two men with total PSA levels of 6 ng/mL, the man who
has 10% free PSA has about a 50% chance of having cancer; the man with
30% free PSA has a 10% chance, and the cancer is more likely to be indolent.
"So the same test that allows you to diagnose prostate cancer also
provides you with important information about its aggressiveness,"
During a panel discussion at the AUA session, other speakers agreed
that free PSA will be very useful in difficult decision-making. Dr. Alan
Partin, of Johns Hopkins, said that free PSA will be useful as a staging
tool and in deciding when to repeat a biopsy.
Dr. Thomas Stamey of Stanford said the test "adds additional information
when total PSA does not give enough," but cautioned "not to let
any patient disappear" on the basis of the test.
A large population-based randomized study from Sweden evaluated the
Dr. Jonas Hugosson, of Ostra Hospital, Goteborg, Sweden, reported the
The investigators concluded that the 3 ng/mL cut-off value combined
The study enrolled almost 10,000 men to an active screening group and
A PSA over 3 ng/mL led to the identification of 137 cancers. A PSA over