Inflammation and Prostate Cancer: A Multidisciplinary Approach to Identifying Opportunities for Treatment and Prevention

SIMPLE SUMMARY: Prostatitis, or the inflammation of the prostate, is frequently observed in the clinic and by research studies, but its relevance to a man’s risk of being diagnosed with prostate cancer, or to his survival after the diagnosis, is not completely understood. In this review, we summarize the current knowledge on the causes of prostate inflammation, as well as the relationship with prostate cancer, with a particular focus on aggressive, defined as a high Gleason score or clinical stage, and lethal stages of disease. We also describe the strengths and weaknesses of the various technologies used to evaluate prostate inflammation in human studies, and we consider the potential of immune therapy and lifestyle interventions to prevent lethal disease and improve outcomes for prostate cancer patients. Future research is needed to better understand the role of prostate inflammation in lethal prostate cancer, and to provide evidence to guide the development of new treatment and prevention strategies to reduce prostate inflammation and improve survival. ABSTRACT: Prostate cancer is a major cause of disease for men globally. Inflammation, an established hallmark of cancer, is frequently observed in the prostate, though its contribution to prostate cancer risks and outcomes is not fully understood. Prostate cancer is biologically and clinically heterogeneous, and there is now evidence that inflammation and immunological characteristics vary by the genomic and mutational landscape of the tumor. Moreover, it is now recognized that risk factor profiles vary between tumor subgroups, as defined by histopathological and molecular features. Here, we provide a review centered around the relationship between inflammation and prostate cancer, with a consideration of molecular tumor features and a particular focus on the advanced and lethal stages of disease. We summarize findings from epidemiological studies of the etiology and role of inflammation in prostate cancer. We discuss the pathology of prostate inflammation, and consider approaches for assessing the tumor immune microenvironment in epidemiological studies. We review emerging clinical therapies targeting immune biology within the context of prostate cancer. Finally, we consider potentially modifiable risk factors and corresponding lifestyle interventions that may affect prostate inflammation, impacting outcomes. These emerging insights will provide some hints for the development of treatment and prevention strategies for advanced and lethal prostate cancer.