The emerging role of the microbiome in bladder cancer: prognostic implications and treatment response

Bladder cancer (BCa) is a histologically and molecularly heterogeneous disease and is one of the leading causes of cancer death globally. The main risk factors are sex (with incidence 3 to 4 times higher in men), tobacco usage, occupational exposure to carcinogens, and persistent infections, such as those caused by Schistosoma haematobium. Urine and the bladder were recently confirmed to be non-sterile, prompting investigations into the urinary and intratumoral microbiomes and their roles in tumor stage, prognosis, and therapy response. In this context, the role of the urinary and intratumoral microbiome in bladder carcinoma is among the most promising areas in translational uro-oncology. Recent evidence demonstrates the presence and diversity of microbial communities in both urine and bladder cancer tissue, with patterns associated with tumor stage and prognosis. Chronic inflammation, genotoxin production, altered carcinogen metabolism, and modulation of the immune microenvironment are biological processes that provide a rationale for the functional role of these microorganisms in the bladder. Furthermore, microbial profiles have been correlated with responses to intravesical therapies (such as BCG - Bacillus Calmette-Guérin) and, potentially, with systemic immunotherapies. The microbiome can help identify predictors of treatment response and potential adjuvant interventions, and offers a non-invasive, translational pathway for diagnosis and surveillance. This review summarizes current evidence on the microbiome in bladder cancer patients and its prognostic and therapeutic potential.