A large cohort study suggests that an initial prostate-specific antigen (PSA) level of 3 ng/mL should be the cutoff for biopsy of the prostate and that men with initial PSA values < 2 ng/mL should be screened at substantially longer intervals than is the current practice. Experts agreed that the study’s findings suggest a new cutoff for prostate biopsy and longer screening intervals for men at very low risk of prostate cancer.

Avoids Unnecessary Procedures

 “These results justify use of a threshold of ≥ 3 ng/mL for prostate biopsy,” stated Meelan Bul, MD, Erasmus University Medical Center of Rotterdam, The Netherlands, who presented the findings of a Dutch cohort study that was part of the European Randomized Study of Screening for Prostate Cancer (ERSPC) at the recent Genitourinary Cancers Symposium held in Orlando, Florida. “This means that we can possibly avoid unnecessary testing, diagnosis, and treatment of less aggressive disease, with the accompanying side effects, by focusing biopsies and other follow-up on men with higher initial PSA levels above 3.0 ng/mL.”

Speaking at a press telecast where these results were highlighted, study senior author Monique Roobol, PhD, of Erasmus University Medical Center said, “These results can also contribute to risk stratification and management of men in PSA-based screening programs. For example, the favorable outcomes in men with initial PSA values of less than 1 ng/mL support prolongation of the screening interval for these men for up to 8 years.”

Study Details

The Dutch cohort study included 42,376 men between the ages of 55 and 74 with an initial PSA value of < 3 ng/mL and no evidence of cancer from 1997 on. Almost 20,000 men were randomly assigned to serial screening PSA tests, and the threshold for biopsy was PSA of 3 ng/mL or higher. The report at the Genitourinary Cancers Symposium focused on 15,758 (79%) men with PSA values < 3.0 ng/mL at the first screening test; men were screened every 4 years.

At baseline, men were stratified according to initial PSA levels < 1 ng/mL (45%), 1 to 1.9 ng/mL (39%), and 1.9 to 2.9 ng/mL (16%). At a median follow-up of 11 years, 915 cancers were detected in the Dutch cohort, which represented less than 6% of study participants. Of these, 733 were found at screening and 182 by clinical exam. The risk of cancer was increased—although still very low—with increasing initial PSA level. A total of 23 prostate cancer deaths occurred over the course of the study, for a mortality rate of 0.15%.

A fourfold increased risk of cancer was seen when men with initial PSA levels < 1 ng/mL were compared with those who had levels of 1 to 1.9 ng/mL; a tenfold increase was observed between those with initial levels < 1 ng/mL compared with 1.9 to 2.9 ng/mL.

Of the 915 cancers detected during the study, 138 were deemed aggressive (ie, definite clinical stage T2c or higher, Gleason score ≥ 8, and PSA level of 20 ng/mL or higher). A 2.7-fold increase was observed between PSA levels < 1 ng/mL and levels of 1 to 1.9 ng/mL, and a 6.2-fold increase of aggressive prostate cancer was observed between PSA levels < 1 ng/mL vs 2 to 2.9 ng/mL.

Dr. Roobol said that PSA level was much more predictive than age for future risk of developing prostate cancer. “The difference between risk in men with initial PSA levels < 1 and 2 ng/mL is much more significant than age,” she noted. ■

Financial Disclosure: Dr. Bul reported no potential conflicts of interest. Dr. Roobol disclosed financial relationships with Beckman Coulter, GlaxoSmithKline, and Gen-Probe.

Reference

1. Bul M, van Leeuwen PJ, Zhu X, et al: Prostate cancer incidence and disease-specific survival in men participating in the ERSPC with an initial PSA less than 3.0 ng/mL. Genitourinary Cancers Symposium. Abstract 7. Presented February 17, 2011.