12 Biopsy remains a safe procedure for prostate cancer detection. Monitoring false-positive results is important because they can also have a psychologic impact on patient health. McNaughton-Collins and colleagues13 reported that 49% of men who received a false-positive result and a later, confirmed normal result thought about prostate cancer either “a lot” or “some of the time” compared with only 18% of those with a normal serum PSA level (P < .001). Such results raise a number of interesting questions regarding the impact of diagnosis on a patient’s Inhibitors,research,lifescience,medical psychologic well-being. The 13-year follow-up of the PLCO may provide additional answers. Although the randomization of the population was near perfect

and resulted in highly comparable populations, the contamination of the control group is a concern in both Inhibitors,research,lifescience,medical studies. The ERSPC report does not describe the control group and its possible screenings. Thus, it is unclear how many patients in the control group were screened and how this unidentified number affected the results. Because there were study centers in different countries, it is possible that the control groups underwent different levels of screening or none at all. It is therefore

difficult to assess the level of homogeneity in screening within the control group. The PLCO trial took measures to minimize Inhibitors,research,lifescience,medical contamination before it began randomization by excluding men who had had more than 1 PSA test in the 3 years previous to 1995. The trial assesses the Inhibitors,research,lifescience,medical screening in the control group by regular surveys, reporting that 9.8% of the control group did in fact have repeated screenings during the study period. An average of these and those who had never been screened was taken to assess contamination of the whole control group. In the PLCO trial, the level of screening in the overall study population was high: 44% of men had at Inhibitors,research,lifescience,medical least 1 PSA test and 55% had at least

1 DRE in the past 3 years. Age at the time of enrollment trials may have further added to the contamination in both the PLCO and ERSPC trials. Recommendations by the American Medical Association14 state that men above 55 should be screened CX-5461 supplier annually. Because patients up to 75 years of age were enrolled in both trials, the study population was most likely, at least in part, already screened. Carter and colleagues15 nearly investigated the influence of age on the chance of curable prostate cancer among men with nonpalpable disease. Younger age was found to be associated with greater probability of curable cancer and more likely to lead to a decrease in prostate cancer mortality. Similarly, Smith and colleagues16 demonstrated that younger age at the time of diagnosis is an independent predictor of better prognosis. The earlier age at diagnosis and stage migration has created a lead-time of at least 3 to 5 years. This lead-time bias is an important consideration in studies demonstrating an improved survival in the PSA screening era.