Chronological Trends of PSA Levels at Diagnosis in Population-based Prostate Cancer Data 2004-2021, a Time Period of Drastic Changes in Screening Guidelines: Potential Implications in Prostate Cancer Diagnosis.

Objective: For the past two decades, there have been serial changes in prostate cancer screening guidelines, which have introduced peculiar chronological patterns in prostate cancer incidence and stage distribution in the United States (US). Most published data do not cover the last guideline change in 2018 and there have been scant data to indicate how prostate-specific antigen (PSA) levels at prostate cancer diagnosis have changed over time. In this paper, which includes an observation period through 2021, we examine chronological trends in PSA levels at diagnosis in population-based prostate cancer data. Materials and methods: We analyzed measurements of PSA levels and other tumor and patient characteristics of 945,797 prostate cancer cases diagnosed between 2004 and 2021, which were captured by the Surveillance, Epidemiology, and End Results (SEER) Program. Chronological trends of age-and race-adjusted mean PSA values, as well as the proportion of high PSA (>=20ng/ml) by year, were analyzed by Joinpoint software, overall and by major racial and age groups. Results: We found three time points indicating changes in the chronological trends of PSA. Mean PSA levels and the high PSA fraction declined up to 2007/2008 (the point at which the first guideline was issued against PSA screening for older men), stayed rather flat until 2011 (close to the time point when the recommendation against PSA screening was issued for all age groups), and thereafter they rose sharply until 2014/2015, when the rising trend began to deescalate. The point estimates for the timing of changes were slightly earlier with the binary measures than for continuous PSA values. The last, more slowly rising trend was more pronounced in younger patients (<75 years) than in older ones. We detected similar Joinpoint patterns for the proportion of advanced stage (regional and distant). Conclusions: Chronological trends of serum PSA levels observed between 2004 and 2021 in the US are generally consistent with a series of changes in US Preventive Services Task Force (USPSTF) screening guidelines that occurred during this period as well as with a shift toward advanced stage at diagnosis.