Roman Gulati, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues assessed the comparative effectiveness of alternative PSA screening strategies using a microsimulation model of prostate cancer incidence in a contemporary cohort of U.S. men. Thirty-five screening strategies were compared that varied by start and stop age, interval, and threshold for biopsy referral.The researchers found that the risk for prostate cancer death was 2.86 percent without screening. The risk was reduced to 2.15 percent (with a 3.3 percent risk of overdiagnosis) with a reference strategy that screens men aged 50 to 74 years annually with a PSA threshold of 4 µg/L for biopsy referral. Use of a higher PSA threshold among older men was associated with a 2.23 percent risk of prostate cancer death and a decrease in the risk of overdiagnosis to 2.3 percent. A biennial screening strategy with longer screening intervals for men with low PSA levels was associated with a 2.27 percent risk of prostate cancer death and a 2.4 percent risk of overdiagnosis. In addition, this strategy correlated with a 59 percent reduction in total tests and a 50 percent reduction in false-positive results.