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A Detailed Evaluation of the Effect of PSA-Based Screening on Morbidity and Mortality of Prostate Cancer: 21-year Follow-up Results of the Rotterdam Section of the European Randomized Study of Screening for Prostate Cancer - Beyond the Abstract

Screening for prostate cancer (PCa) with prostate-specific antigen (PSA) remains controversial. While the European Randomized Study of Screening for Prostate Cancer (ERSPC) previously demonstrated that PSA screening results in a reduction in PCa mortality, it has also been associated with overdiagnosis and the possibility of overtreatment.1 In addition to reducing prostate cancer-specific mortality (PCSM), a legitimate secondary endpoint of screening is to mitigate the burden of PCa by reducing metastatic disease (M+). This commentary focuses on the 21-year findings of the Rotterdam section of the ERSPC, which provide significant insights into the long-term impact of PSA screening on PCSM and M+.2

The study found a statistically significant reduction in PCSM relative rate of 27% among men aged 55-69 years at randomization (core age group) who underwent PSA-based screening compared with those who were offered no active screening. On the contrary, no statistical difference was observed in PCSM men aged ≥70 yr at the time of randomization (Fig 1). Although the reduction in the core age group is slightly lower than the ERSPC Rotterdam's 16-year follow-up PCSM reduction of 33%, the absolute risk difference of PCSM between the two groups has increased from 0.32% to 0.41%.1 This increase results in a lower number of men needed to invite (NNI; from 303 to 243 men) and number of men need to diagnose (NND; from 18 to 14 men), which is a favorable finding regarding overdiagnosis. Similar observations were made in the Swedish arm of the ERSPC after 22 years of follow-up.3

1Pca_Mortality_graph.jpg
Furthermore, the study found a relative rate reduction in overall M+ of 33% in favor of screened men. With increased follow-up available, the reduction of overall metastasis coincides with a lower NNI (121 vs 328 men at 12-yr follow-up) and NND (7 vs 12 men at 12 yr follow-up). The main reason for the reduction in M+ was the prevention of M+ at diagnosis in the screened group, which was found to be twice as low as the non-screened group. However, the overall reduction was somewhat weakened by the increasing number of men in the screened group who developed M+ after diagnosis (Fig 2). Considering half of the M+ cases detected during the follow-up of the screened group were identified in men who were diagnosed in the first screening round, a possible explanation for this observation might be the cross-sectional design effect of the trial by offering a first PSA test to men aged anywhere between 55 and 74 yr.

2_metastatic_pca_overall_graph.jpg

Written by: Ivo I. de Vos, MD & Monique J. Roobol, PhD, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands

References:

  1. Hugosson J, Roobol MJ, Månsson M, Tammela TLJ, Zappa M, Nelen V, et al. A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer. Eur Urol. 2019;76(1):43-51.
  2. de Vos II, Meertens A, Hogenhout R, Remmers S, Roobol MJ, Group ERS. A Detailed Evaluation of the Effect of Prostate-specific Antigen-based Screening on Morbidity and Mortality of Prostate Cancer: 21-year Follow-up Results of the Rotterdam Section of the European Randomised Study of Screening for Prostate Cancer. Eur Urol. 2023.
  3. Frånlund M, Månsson M, Godtman RA, Aus G, Holmberg E, Kollberg KS, et al. Results from 22 years of Followup in the Göteborg Randomized Population-Based Prostate Cancer Screening Trial. J Urol. 2022;208(2):292-300.
  4. Roobol MJ, Remmers S, Nieboer D. 41 - Prostate cancer screening in the elderly: A yes or no issue? Long term follow-up data from ERSPC Rotterdam. European Urology Open Science. 2020;19:e158-e9.
  5. Van Poppel H, Hogenhout R, Albers P, van den Bergh RCN, Barentsz JO, Roobol MJ. Early Detection of Prostate Cancer in 2020 and Beyond: Facts and Recommendations for the European Union and the European Commission. European Urology. 2021;79(3):327-9.
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