Reimagining prostate cancer screening: the IMPACT of germline mutations.

Abstract

Structured prostate-specific antigen (PSA) screening allows for the early detection of prostate cancer in men aged 55–69 years with a reduction in the incidence of metastatic disease at presentation and cancer-specific mortality at 16 year's follow-up. 1 Hugosson J Roobol MJ Månsson M et al. A 16-yr follow-up of the European randomized study of screening for prostate cancer. Eur Urol. 2019; 76: 43-51 Summary Full Text Full Text PDF PubMed Scopus (182) Google Scholar Population-based screening has been associated with a non-negligible risk of overdiagnosis (ie, the detection of cancers that would not have caused symptoms), which can be as high as 40%, and has limited its adoption at a large scale 2 Martin RM Donovan JL Turner EL et al. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: the CAP randomized clinical trial. JAMA. 2018; 319: 883-895 Crossref PubMed Scopus (210) Google Scholar such that no national prostate cancer screening programmes exist in the USA and Europe. 3 Van Poppel H Hogenhout R Albers P van den Bergh RCN Barentsz JO Roobol MJ A European model for an organised risk-stratified early detection programme for prostate cancer. Eur Urol Oncol. 2021; (published online Aug 4)https://doi.org/10.1016/j.euo.2021.06.006 Summary Full Text Full Text PDF Scopus (11) Google Scholar Restricting the use of repeated PSA testing to men at risk of early-onset disease because of a family history of prostate cancer or germline mutations has been proposed as a means of improving the effectiveness of screening. 2 Martin RM Donovan JL Turner EL et al. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: the CAP randomized clinical trial. JAMA. 2018; 319: 883-895 Crossref PubMed Scopus (210) Google Scholar , 4 Gandaglia G Albers P Abrahamsson PA et al. Structured population-based prostate-specific antigen screening for prostate cancer: the European Association of Urology Position in 2019. Eur Urol. 2019; 76: 142-150 Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar , 5 Page EC Bancroft EK Brook MN et al. Interim results from the IMPACT study: evidence for prostate-specific antigen screening in BRCA2 mutation carriers. Eur Urol. 2019; 76: 831-842 Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective studyAfter the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings. Full-Text PDF Open Access