Why do African–American men face higher risks for lethal prostate cancer?

African–American men in the USA have a higher incidence of and mortality from prostate cancer (PCa), with a longstanding debate about the cause for these worse outcomes. This review examines differences in tumour biology and socioeconomics for African–American and Non-Hispanic White (NHW) men to answer the question ‘why AA men face higher risks for lethal PCa’ and draw a management consensus to redress the imbalance. RECENT FINDINGS: Recent evidence from over the past 2 years suggests the reasons why African–American men face a higher risk of lethal PCa are multifactorial, with contributions from differences in tumour biology as well as socioeconomic and healthcare access factors. Regarding tumour biology, genomic and transcriptome profiling suggests African–American men have upregulated expression of genes related to inflammatory pathways with downregulation of DNA repair genes. In contrast, NHW men have higher DNA repair pathways and metabolic pathways involving glycolysis and cell cycle activity. In addition, epidemiological evidence suggests equal healthcare access ensures equal PCa specific outcomes, implying African–American men's disease is not inherently more lethal. However, differences in tumour biology remain, which may explain specific differences in PCa incidence and the clinical findings of African–American men's increased response to immunotherapy and radiotherapy in recent trials. SUMMARY: Regardless of racial differences in disease outcomes and the factors causing them, African–American and NHW men seem to have diseases unique to their ancestry. This supports the exploration of personalized PCa treatment approaches, leveraging translational basic science research to uncover these differences and devise specific individualized methods therapeutic regimes to address them.