Single PSA at midlife predicts advanced prostate ca risk

ANAHEIM, California—A single PSA test at mid-life can predict who will develop advanced prostate cancer within the next 25 years, according to a study of archived serum from more than 20,000 Swedish men reported at the American Urological Association annual meeting (abstract 1876).

"In this large unscreened representative population, a single PSA measure at age 44 to 50 was a very strong predictor of later diagnosis of prostate cancer of unquestionable significance," said senior investigator Hans G. Lilja, MD, PhD, attending research clinical chemist at Memorial Sloan-Kettering Cancer Center.

This study was a re-analysis of earlier work by Dr. Lilja and his colleagues showing that a single PSA test at age 44 to 50 could predict prostate cancer in general for up to 25 years. The new study was meant to answer the question of how many of those cancers are clinically important (stage T3 or higher or metastatic disease at diagnosis).

The researchers analyzed archived serum from 21,277 men, and matched each case with three controls based on age and date of blood sample. They used conditional logistic regression to determine the association between PSA or kalikrein 2 (KLK2 or hK2) levels and development of advanced prostate cancer.

Two-thirds of the 161 cases diagnosed with advanced prostate cancer occurred in men with PSAs in the top 20% of PSA levels (0.9 ng/mL or higher before age 50), Dr. Lilja reported (see Table).

The median delay from baseline to prostate cancer diagnosis was 17 years, and plasma levels for both markers were strongly associated with development of advanced cancer (P < .01).

Dr. Lilja noted that even small elevations in PSA were associated with increased risk of being diagnosed with advanced prostate cancer by age 75. A 1 ng/mL increase in total PSA was associated with a 3.19-fold increase in the odds of a future advanced prostate cancer diagnosis.

The highest PSA levels at age 44 to 50 were associated with the highest risk: About 50% of advanced cancers occurred in subjects with baseline PSA within the top 10% of PSA levels (PSA of 1.2 ng/mL or higher before age 50); more than 65% occurred in the top 20%.

This raises the question of whether prostate cancer screening and treatment should be more narrowly focused on those men who are at the highest risk for advanced disease, he said.

Current guidelines call for yearly screening from age 50 to age 70. Dr. Lilja's data suggest that nearly all advanced cancers could be found early by intense screening of high-risk men.

Treatment also becomes an issue. "There is a drug to prevent prostate cancer (finasteride, Proscar), but few use it. Should we focus chemoprevention on men at highest risk?" Dr. Lilja asked. "These data need to be validated in independent study cohorts, as they make important arguments for use in the revision of current screening guidelines."