Early-Onset Prostate Cancer: Epidemiology, Risk Factors, Biology, Clinical Features, Management, and Early Detection

The incidence of early-onset prostate cancer (EOPC) is rising, and by 2045 a 24.5% increase in cases and a 50% rise in mortality are projected. Accumulating evidence indicates that EOPC represents a distinct disease entity, characterized by unique molecular features, risk factor profiles, and clinical behavior that differ from standard-onset prostate cancer (SOPC). Nevertheless, research in this field remains nascent, and no consensus exists regarding the optimal management of EOPC. We synthesize current evidence on the epidemiology, molecular pathology, clinicopathological characteristics, survival, management, and early detection of EOPC. EOPC exhibits a distinctive molecular landscape, with TMPRSS2-ERG fusions occurring in 63-90% of cases as a hallmark alteration, whereas mutations in PTEN, SPOP, and CHD1 are significantly less frequent. Notably, the prevailing focus on hereditary EOPC has inadvertently led to the neglect of sporadic cases, which dominate clinical practice. Although localized EOPC confers no significant prognostic advantage over SOPC, high-risk or metastatic early-onset disease substantially elevates prostate-cancer-specific mortality. By critically appraising the existing evidence, we identify key knowledge gaps, such as the understudied sporadic EOPC subgroup and the lack of dedicated clinical trials, and propose future research directions to inform early detection and optimize therapeutic strategies for this unique patient population.