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," he said.
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 diagnostic ability of PSA with a cut-off value of 3 ng/mL and the possible benefit of adding percent free PSA.
Dr. Jonas Hugosson, of Ostra Hospital, Goteborg, Sweden, reported the results from the European Randomized Study of Screening of the Prostate at the AUA annual meeting.
The investigators concluded that the 3 ng/mL cut-off value combined with percent free PSA of less than 18% offers better detection and better specificity than PSA alone at a 4 ng/mL cut-off.
The study enrolled almost 10,000 men to an active screening group and evaluated a subgroup of 608 men who had PSA levels over 3 ng/mL and had undergone biopsy.
A PSA over 3 ng/mL led to the identification of 137 cancers. A PSA over 3 and percent free PSA of less than 18% found 120 cancers. A PSA over 4 led to the diagnosis of 105 cancers. And PSA over 4 plus percent free PSA less than 18% identified 97 cancers. Over half of all the cancers were not palpable, Dr. Hugosson reported.