Editorial Comment to Prostate-specific antigen-based prostate cancer screening: Past and future.

Abstract

Although prostate-specific antigen (PSA)-based prostate cancer screening remains controversial, Alberts et al. have provided this very comprehensive and objective review.1 The results from two large, randomized, controlled trials have addressed the issue of screening for prostate cancer. The European Randomized Study of Screening for Prostate Cancer found that prostate cancer death decreased by approximately 21% among men aged 55–69 years as a result of PSA screening.2 In contrast, the United States Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) did not find that PSA screening resulted in a difference in 10-year cancer-specific survival rates.3 Based on these findings, considering the benefits and harms of the service, the U.S. Preventive Service Task Force recommended against PSA-based screening. Nevertheless, the 35% reduction in mortality rates due to prostate cancer in the USA between 2005 and 1990 might have been a result of PSA screening, and subsequent timely and appropriate treatment.4 The background of the screened populations needs to be considered to understand and adopt the findings of the two clinical trials of PSA screening. The rates of men aged ≥50 years or older who are exposed to PSA screening in the USA, and European and Asian countries including Japan are approximately 75%, 5–20% and <5%, respectively.4, 5 High exposure rates to PSA screening causes high contamination rates in the control arms of trials. The contamination rates of PSA screening were 20% and 52% in the European Randomized Study of Screening for Prostate Cancer and PLCO trials.4, 6 Furthermore, the rates of receiving a second screening (prostate biopsy) also differ between the two trials, such as 85.9% in European Randomized Study of Screening for Prostate Cancer and 23.5% in PLCO.4, 6 The rates of patients with stages IV and III disease were 2.7% and 1.9%, respectively, in the PLCO trial, and the rates of those with stage IV disease did not significantly differ between the screened and control arms. When considering the Japanese population, the rates of patients with stage IV and stage III were 21% and 19%, respectively.7 The characteristics of the populations that would be screened in the PLCO and in Japan obviously differ, therefore, one might consider these factors when applying the results of PLCO to the Japanese population. The mortality rate of prostate cancer in Japan is increasing, and the number of prostate cancer deaths is expected to be 2.8-fold higher in 2020 than in 2000.4 The best available option must be established to decrease the rate of prostate cancer death. The Japanese Urological Association recommends that PSA screening should be offered to all men at risk of developing prostate cancer, with fact sheets showing the updated benefits and drawbacks of screening for prostate cancer.4 In detail, men aged 50 years or older are recommended to begin PSA screening, whereas men with a family history of prostate cancer are recommended to begin PSA testing from 40 years-of-age. Men with PSA levels of 1.0 ng/mL or lower are recommended to be screened every 3 years, whereas men with PSA levels of greater than 1.0 ng/mL were recommended to be screened annually. In terms of the cut-off of PSA for biopsy, the indication is set at 4.0 ng/mL in general. Alternative cut-offs are set in an age-specific manner (50–64 years, 3.0 ng/mL; 65–69 years, 3.5 ng/mL; 70 years or older, 4.0 ng/mL).4 In terms of drawbacks, PSA screening might result in overdiagnosis of prostate cancer by detecting insignificant cancer that might not require immediate treatment. Several currently active surveillance criteria, including the Prospective Validation of Active Surveillance in Prostate Cancer, are used to predict clinically insignificant prostate cancer. Although active surveillance criteria are optimal for detecting very low-risk prostate cancer, significant discrepancies between diagnostic biopsies and surgical specimens as a result of Gleason score upgrading and upstaging have also been uncovered.8 As the authors showed, the incorporation of multiparametric magnetic resonance imaging or novel serum markers, such as proPSA or the Beckman Coulter Prostate Health Index, into current active surveillance criteria might be useful to avoid the future misclassification of insignificant cancer. None declared.