Molecular Landscape of Prostate Cancer Across Age Groups: Impact on Prognosis and Treatment Outcomes.

Abstract

Prostate cancer (PC) has long been considered a disease of older men. Still, a significant and concerning rise in diagnoses among younger men has revealed a biologically distinct and more aggressive clinical entity: early-onset prostate cancer (EO-PC). This comprehensive review synthesizes the molecular and clinical evidence to demonstrate that PC is not a single disease, but a collection of distinct entities delineated by patient age. EO-PC is characterized by a strong genetic component, unique fusion events like TMPRSS2-ERG, and a highly plastic phenotype driven by intense Notch signaling and a hybrid epithelial-to-mesenchymal transition. In stark contrast, late-onset prostate cancer (LO-PC) is defined by a higher mutational burden, an epigenetic "field defect" that accumulates with age, and a predominantly immunosuppressive tumor microenvironment. These profound biological differences have significant implications for diagnosis, prognosis, and therapeutic strategies. Traditional prognostic tools, such as the Gleason score, are often insufficient to capture the full spectrum of risk in younger men. The divergent molecular landscapes of EO-PC and LO-PC necessitate a fundamental shift from a standard approach to an age-aware precision medicine framework. This review highlights key therapeutic targets and underscores the critical need for a new paradigm in PC management to improve patient outcomes.