Genitourinary malignancies are characterized by marked heterogeneity in tumor biology, clinical behavior and therapeutic outcomes. Despite significant progress in surgical and systemic treatments, resistance to therapy remains a major challenge, highlighting the need to identify additional host-related determinants of disease progression and treatment response. Within this framework, converging experimental and clinical evidence indicates that host-associated microbial ecosystems may influence key biological processes involved in tumor–host interactions, including immune modulation, metabolic regulation and inflammatory pathways. Altered microbial profiles have been associated with oncogenic signaling, changes in the tumor microenvironment and differences in clinical benefit from systemic therapies, particularly immunotherapeutic approaches. This review brings together preclinical, translational and clinical evidence on the involvement of microbiota in renal, prostate, bladder and testicular cancers, with attention to biological mechanisms and clinically meaningful correlations with disease characteristics. While current data are largely observational, early interventional studies suggest that modulation of microbial ecosystems may influence therapeutic activity in selected clinical settings. Collectively, these findings support microbiota as a relevant component of genitourinary cancer biology with potential implications for precision medicine approaches.
Caramella et al. (2026) studied this question.