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

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.

Keywords: epidemiology; immune; inflammation; lifestyle; pathology; prostate cancer; tumor microenvironment.

Figure 1

The histological classification of prostatic inflammatory infiltrates. Prostate inflammation is classified according to the inflammation extent (focal, ˂10%; multifocal, 10–50%; or diffuse, >50%) and grade (mild, ˂100 cells/mm²; moderate, 100–500 cells/mm²; or severe, >500 cells/mm²) in each tissue location (glandular, periglandular, and stromal). (Adapted from Nickel et al. [43]).