Prostate Cancer: Genetics, Epidemiology, Diagnosis, Therapeutic Advances, and Emerging Alternative Approaches

Abstract

Prostate cancer (PCa) remains the second most commonly diagnosed malignancy in men and a leading cause of cancer-related mortality worldwide. Its etiology is multifactorial, shaped by age, ethnicity, environmental exposures, lifestyle factors, and a strong hereditary component, with germline mutations in DNA repair genes such as BRCA1/2, ATM, CHEK2, and HOXB13 playing a pivotal role in susceptibility and disease progression. Advances in molecular biology have revealed profound tumor heterogeneity and the contribution of androgen receptor signaling, epigenetic modifications, and microenvironmental interactions to disease pathophysiology. Screening and diagnostic approaches have evolved beyond conventional prostate-specific antigen (PSA) testing and digital rectal examination (DRE) to incorporate multiparametric magnetic resonance imaging (mpMRI), prostate-specific membrane antigen positron emission tomography (PSMA-PET), and emerging biomarker panels, enabling earlier detection and risk stratification. Treatment modalities range from active surveillance for indolent disease to surgery, radiation, androgen deprivation therapy, and systemic agents, including next-generation androgen receptor inhibitors, chemotherapy, PARP inhibitors, and radioligand therapies. Despite these advances, treatment resistance, adverse effects, and risk of overtreatment persist, driving exploration of complementary strategies such as immunotherapy, phytochemicals, nanomedicine, and gene-based interventions. This review provides a comprehensive synthesis of genetic determinants, epidemiological trends, diagnostic strategies, therapeutic advancements, and alternative approaches to prostate cancer, emphasizing the need for precision medicine and multidisciplinary care to improve survival and quality of life.