Prostate cancer screening in BRCA and Lynch syndrome mutation carriers

Prostate cancer (PrCa) remains a major public health burden worldwide. Screening programs have been established using the most efficient biomarker to date-prostate-specific antigen (PSA)-with the goal of earlier detection of this disease, which is thought to translate to a reduction in PrCa mortality. However, these screening programs have proved to be controversial following the publication of the two large, randomized, population-based studies in the United States and Europe. There is a recognized need for more refined screening strategies to address some of the deficiencies highlighted in these trials, which include the overdiagnosis and overtreatment of clinically indolent disease. One such strategy could be to include inherited genetic variants in population risk stratification to identify those at higher risk who might benefit more from screening. The genetic component for PrCa risk has been documented from case control and twin studies. The genetic variants include common variants discovered by genome-wide association studies (GWAS). However, their clinical application-including their utility in screening programs-is as yet undefined. There are, however, moderate to rare genetic variants, which confer a much higher risk of PrCa (e.g., BRCA1/2 and mismatch repair [MMR] repair genes). There is more research evidence on the clinical effect of germ-line mutations in these genes; mutation carriers are more likely to develop aggressive PrCa with worse survival. A targeted screening approach might be beneficial if earlier diagnosis, and hence treatment, was to translate into improved outcomes. Clinical trials are currently underway to investigate this further.