Identifying factors associated with prostate cancer progression and survival in African American men: The RESPOND Cohort

African American (AA) men have a >80% higher incidence and are more than twice as likely to die from prostate cancer (PCa) than white men. The reasons for the high burden relating to poor outcomes of PCa among AA men are largely unknown. RESPOND is a nation-wide and comprehensive effort to understand PCa health disparities,

with research focused on the role of stress and the contextual environment, access to care and treatment, inherited susceptibility, tumor somatic genetics, the inflammatory tumor microenvironment, as well as the integration of these factors in the diagnosis of aggressive disease. AA men, diagnosed with PCa between 2015

and 2020, have been sampled and recruited from cancer registries in 7 states (California, Georgia, Louisiana, Michigan (Detroit Metropolitan area), New Jersey, Texas, and New York). By December of 2023, the cohort will include >12,700 AA men with PCa who completed a baseline survey, >7,600 who provided saliva/germline DNA

and tumor samples obtained for >3,400. Over the next 5-years, we will leverage the RESPOND recruitment infrastructure and research expertise to update comorbidities, lifestyle behaviors, experience of stress, access to care, and neighborhood environmental data, as well as to obtain information on PCa oncologic outcomes

including disease progression/recurrence (P/R) and mortality. Long-term follow-up of this cohort is essential since the development of progressive disease may take several years after diagnosis. These data will be used to address a number of scientific questions and hypotheses aimed at understanding key social and biological

factors and their inter-relationships that contribute to disease P/R and survival in this high-risk population. In Aim 1, we will examine multi-level provider, geospatial and personal factors that define access to care and their relationship to PCa, P/R and survival as well as patient-reported outcomes. In Aim 2, we will investigate

residence in persistently disinvested neighborhoods and modification by chronic exposure to life-course structural and social stressors on PCa aggressiveness, P/R and survival. In Aim 3, we will evaluate the impact of lifestyle factors, comorbid conditions and genetic risk factors on PCa P/R and mortality. Lastly, in Aim 4, we

will leverage deep learning approaches applied to histopathologic images to improve prediction of PCa P/R and survival in AA men. Each aim addresses a distinct research domain (access to care, social environment/stress, lifestyle and genetic factors and tumor features), yet, when studied together in a single cohort, scientific synergy

is gained and a far more comprehensive picture of the major factors that contribute to PCa P/R and PCa survival in AA men. We expect these findings to have broad reaching significance and address numerous challenges in the clinical management and prevention of P/R in AA men, and ultimately improve health outcomes.

Furthermore, we expect RESPOND to become an invaluable resource for advancing our understanding of the intersecting multilevel factors contributing to the longstanding high burden of PCa among AA men.