A large prostate cancer screening study of middle-aged and elderly men that included repeat visits showed that an initial Prostate-Specific Antigen (PSA) score of 3.0 ng/ml appears to be an appropriate minimum cut-off level to determine the need for biopsy. Few men in the study with low first-time PSAs below 3.0 developed prostate cancer and died from the disease. Researchers also found that within this group of low-risk men, the higher the initial PSA, the greater the risk of developing prostate cancer and more aggressive disease, and of dying from prostate cancer.

The research was presented at ASCO's fourth annual Genitourinary Cancers Symposium.

"We now know more about prostate cancer detected by PSA screening in men with initial PSA scores of less than 3.0," said lead author Meelan Bul, M.D., Ph.D., candidate, Department of Urology at Erasmus University Medical Center in Rotterdam, The Netherlands. "Our results strengthen the justification of the use of PSA in risk stratification for screening purposes. 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 PSAs above 3.0." She noted that while PSA level by itself doesn't necessarily enable doctors to distinguish between cancer and benign conditions, the results are used to help decide if further testing for prostate cancer is warranted.

In the study - part of the larger European Randomized Study of Screening for Prostate Cancer - researchers analyzed both incidence of and deaths from prostate cancer among 42,376 men between ages 55 and 74 living in the Rotterdam area. Participants in the population-based study were randomized to either screening or a control arm. Of the 42,376 men, 19,950 were initially screened and biopsies were recommended for those with PSA scores of 3.0 or above only, with four-year screening intervals.

Researchers were interested in the number of men with an initial PSA value of less than 3.0 who would be diagnosed with prostate cancer and the number of men who would die of this disease during long-term follow-up. They found 15,758 (79 percent) of the men had an initial PSA under 3.0. Between 1993 and 2008, 915 of those men were diagnosed with prostate cancer - with a median follow up of 11 years - with only 23 deaths. Of the 915 diagnosed, 182 were detected between screenings, often indicating a faster-moving disease, and overall, 169 (1.1 percent) were determined to be aggressive prostate cancers.

Overall, prostate cancer incidence and deaths increased significantly with higher PSA levels. Only 129 men (1.8 percent) of 7,126 men with PSA scores below 1.0 were eventually diagnosed with prostate cancer, with only three deaths (.04 percent). Of the 6,156 men with PSA scores between 1.0 and 1.9, 415 (6.7 percent) developed prostate cancer, with 11 deaths (.18 percent). The researchers found 2,476 men with PSA levels between 2.0 and 2.9, with 371 cases of prostate cancer (15.7 percent) and nine deaths (.36 percent).

"The 3.0 score appears to be an appropriate threshold for the study because approximately 80 percent of the men ages 55 to 74 years had a PSA under 3.0, with few deaths from prostate cancer. At the same time, we still found a group of men with aggressive prostate cancer and we need improved methods of detecting aggressive disease. These results can contribute to better individual management of men in PSA-based screening programs," said senior investigator Monique Roobol, Ph.D., an epidemiologist in the Department of Urology at Erasmus University Medical Center.

The investigators suggested that future research focus on improving the detection of aggressive prostate cancers, including better risk stratification methods and new molecular and genetic markers.