Obesity and urogenital cancer in men: biological mechanisms and clinical implications

Obesity is a highly prevalent global health issue, affecting more than 890 million adults worldwide, with over 2.5 billion adults being overweight. In men, obesity is a leading determinant of morbidity and premature mortality, contributing to cardiovascular, metabolic and oncological diseases, including urogenital cancers, such as renal, bladder, and prostate cancers, as they are highly susceptible to the adverse effects of obesity on metabolic, inflammatory, hormonal, and immune pathways. Excess adiposity predominantly acts as a biological modifier of tumor aggressiveness, progression, and clinical outcomes. Chronic inflammation, insulin resistance, dysregulation of the insulin-like growth factor axis, adipokine imbalance, oxidative stress, and endocrine disruption create a pro-tumorigenic environment that facilitates malignant transformation and disease progression. In men, these mechanisms are amplified by increased visceral fat and obesity-related hypogonadism. Renal cell carcinoma (RCC) is the urogenital malignancy most strongly associated with obesity, with an approximately 30–35% increase in RCC risk for every 5 kg/m2 increase in body mass index (BMI). Globally, RCC accounts for approximately 2.2% of all newly diagnosed cancers, with more than 430,000 new cases annually, highlighting its growing public health burden. Conversely, in bladder and prostate cancers, obesity, besides increasing the risk of cancer development, affects tumor characteristics, treatment response, and disease outcomes. Interestingly, typical anthropometric measurements, such as BMI, are insufficient to determine obesity-related cancer risk, thus, a better evaluation of body composition, with determination of fat mass, fat-free mass, and intra- and extra-cellular water through bioelectrical impedance analysis, is needed. This review discusses the link between obesity and development of urogenital cancers, its potential negative influences on treatment responses and clinical outcomes, as well as the putative pathogenic mechanisms underlying these associations. We focused on kidney, bladder, and prostate cancers, excluding testicular and penile tumors, for which the association between obesity and cancer appears to be weaker.

Obesity; Urogenital cancer; Renal cancer; Bladder cancer; Prostate cancer; Metabolic dysfunction; Men’s health

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