The Intratumoral Microbiota in Prostate Cancer: Mechanisms, Microbial–Androgen Crosstalk, and Urinary Exfoliative Signatures for Liquid Biopsy Development

Abstract

Prostate cancer [PCa] is the second most prevalent malignancy diagnosed in men worldwide, constituting a considerable public health challenge due to the inadequacies of existing diagnostic methods focused on prostate-specific antigen [PSA] testing, multiparametric magnetic resonance imaging [MRI], and invasive biopsy. The recent paradigm shift towards viewing solid tumors as complex ecosystems has revealed the intratumoral microbiota, a community of bacteria, viruses, and fungi residing within the tumor microenvironment [TME] as a crucial regulator of carcinogenesis. The origin, spatial dynamics, and mechanistic functions of the prostate intratumoral microbiota are summarized in this thorough review. We present "The Prostate Microbial Triad," a novel conceptual framework that describes the co-evolutionary interaction of microbes, resident immune cells, and malignant epithelium. We explore particular mechanisms such as microbial reprogramming of tumor immunology and metabolism, the proposed "Microbial–Androgen Crosstalk Model" specific to PCa, and microbe-induced genomic instability. In order to create reliable liquid biopsies, we suggest a translational pipeline that connects tumor-resident microbes to urine signals through the "Microbial-Extracellular Vesicle [EV] Pathway," and we support multi-omics integration [metagenomics, metabolomics, and spatial transcriptomics] driven by machine learning. Decoding and utilizing the prostate intratumoral microbiome, according to this review, is a frontier with unmatched potential to transform PCa diagnostics by enabling accurate, non-invasive detection and risk stratification.