Prostate Cancer: Current Evidence Weighs Against Population Screening
Authors: P. Boyle, O. W. Brawley
Journal: CA A Cancer Journal for Clinicians (2009)

Prostate–specific antigen (PSA) measurement, obtained from a simple blood sample, has been widely proposed as a screening tool for prostate cancer, which is currently the leading cancer diagnosis in men in several developing countries.1 In many parts of the world, the PSA test is now widely used, and is frequently used indiscriminately. For example, in a cohort of greater than half a million men aged 70 years assembled from 104 US Veterans Administration hospitals during 2002 and 2003, 56% of elderly men had a PSA test (64% of men ages 70–74 years and 36% of men aged 85 years).2 PSA screening has remained a controversial topic, and findings from 2 large randomized trials have been eagerly awaited. The PSA test was first approved by the US Food and Drug Administration in 1986 for monitoring progression in patients with prostate cancer. It was later approved for the detection of disease in symptomatic men and has not been approved for screening asymptomatic men.3 In 1991, Catalona et al4 published results from a large series of men in whom PSA was measured and concluded that the screening program was able to identify patients at a high risk for prostate cancer. For the purposes of evaluating PSA as a screening tool, the absence of a parallel control group was a major handicap; the study simply involved testing levels of PSA in a large series of consecutive male patients. It demonstrated that PSA could be used to help diagnose early stage prostate cancer. It did not address the question of whether PSA screening reduces the prostate cancer mortality rate or saves lives. Findings from prospective randomized clinical studies were/are desperately needed. To our knowledge, to date 4 randomized trials have investigated the efficacy of prostate cancer screening, mainly using the PSA test. The Quebec study5,6 was proclaimed as the first randomized trial to demonstrate the efficacy of screening for prostate cancer. Labrie et al5 presented the data in the plenary session at the annual meeting of the American Society of Clinical Oncology in Los Angeles, California, in 1998. They reported death rates of 48.7 per 100,000 in unscreened men and 15 per 100,000 in screened men, with a claimed odds ratio of 3.25 in favor of screening. This analysis was widely criticized as flawed. It excluded men assigned to the screening group who were invited to screening and did not participate. Reanalysis with a more appropriate intention–to–screen method found a 16% excess of deaths in the group invited to screening compared with those in the control group. The reanalysis strongly suggested that the original findings were significantly affected by selection bias.7 In other words, men who were invited to screening may have opted to accept the invitation because they were more healthy than men who refused the invitation. To exclude this latter group biases the data and the findings.8 The second randomized trial to be published came from Sandblom et al in Sweden9 and reported a 47% higher rate of diagnosis in screened men than in controls. The intention–to–screen analysis of the data calculated the relative risk of death from prostate cancer to be 1.04 (ie, a [statistically nonsignificant] 4% increase in the risk of death from prostate cancer