The Role of Genitourinary Microbiome in Male Cancer Etiology and Progression: Insights from Next-Generation Sequencing and Meta-Omics

Male genitourinary (mGU) malignancies, including prostate, bladder, kidney, testicular, and penile cancers, represent a clinically and epidemiologically significant subset of global cancer burden. Although well-established etiological factors such as genetic mutations, androgen signaling, and environmental exposures contribute to tumorigenesis, the underlying mechanisms remain ill-defined. Recent advances in next-generation sequencing and metagenomics technologies have facilitated a deeper understanding of the human microbiome, revealing its potential role in carcinogenesis. While the gut microbiome has been extensively studied, emerging evidence indicates that site-specific microbial communities within the genitourinary (GU) tract may significantly influence cancer susceptibility, progression, and therapeutic outcomes. Accordingly, this review aims to comprehensively summarize the current evidence examining the relationship between the GU microbiome and the development, progression, and treatment of mGU cancers. To provide the specific context, relevant publications were collected from Google Scholar, PubMed, Science Direct, Dimension AI, and EBSCO Host using specific keywords such as “bladder cancer”, “dysbiosis”, “genitourinary”, “genitourinary cancer”, “microbiome”, “pathogens”, “penile cancer”, “prostate cancer”, “renal cancer”, “testicular cancer”, “urogenital microbiome”. We did not add any limits to the publication date during the inclusion of papers. However, it is noteworthy that the initial reports, including the aforementioned keywords, have been published since 2015. Emerging evidence highlights a significant association between the dysbiosis of the GU microbiome and the development of mGU cancers. Notably, an increase in bacterial richness and species diversity has been correlated with a rapid progression of these cancers, suggesting that such features may be explored as potential candidate biomarkers. Advanced sequencing and meta-omics technologies have enabled the identification of distinct microbial signatures with emerging diagnostic, prognostic, and therapeutic potential. Despite these advancements, the understanding of the functional and mechanistic roles of microbiota, particularly within the penile and seminal environments, remains limited.