Clinical Applications of the Gut Microbiome in Genitourinary Cancers

Recently recognized as one of the hallmarks of cancer, the microbiome consists of symbiotic microorganisms that play pivotal roles in carcinogenesis, the tumor microenvironment, and responses to therapy. With recent advances in microbiome metagenomic sequencing, a growing body of work has demonstrated that changes in gut microbiome composition are associated with differential responses to immune checkpoint inhibitors (ICIs) because of alterations in cytokine signaling and cytotoxic T-cell recruitment. Therefore, strategies to shape the gut microbiome into a more favorable, immunogenic profile may lead to improved responses with ICIs. Immunotherapy is commonly used in genitourinary (GU) cancers such as renal cell carcinoma, urothelial cancer, and to a limited extent, prostate cancer. However, a subset of patients do not derive clinical benefit with ICIs. Gut microbiome-based interventions are of particular interest given the potential to boost responses to ICIs in preclinical and early-phase prospective studies. Novel approaches using probiotic therapy (live bacterial supplementation) and fecal microbiota transplantation in patients with GU cancers are currently under investigation.