From etiology to precision oncology: a systematic review of the causes and evolving treatments of prostate cancer

Background Prostate cancer remains one of the most frequently diagnosed malignancies and a leading cause of cancer-related mortality among men globally. Its development is driven by a complex interaction of genetic susceptibility, molecular alterations, hormonal signaling, environmental exposures, and lifestyle-related factors. This systematic review synthesizes current evidence on the etiological mechanisms and evolving therapeutic landscape of prostate cancer. Methods A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Literature published between January 2010 and December 2025 was searched in PubMed, Scopus, and Web of Science databases. Eligible studies included original research, clinical studies, translational studies, and experimental investigations evaluating prostate cancer etiology, molecular mechanisms, risk factors, biomarkers, or therapeutic interventions. Results The review included 29 studies encompassing epidemiological cohorts, clinical studies, genomic analyses, tissue-based investigations, and preclinical experimental studies. Evidence demonstrated that prostate cancer etiology involves multiple interconnected pathways, including androgen receptor signaling, DNA repair alterations, genomic instability, chromatin remodeling, metabolic reprogramming, and inflammatory mechanisms. Genetic variants, including single nucleotide polymorphisms and polygenic risk scores, were associated with disease susceptibility, aggressiveness, treatment response, and toxicity outcomes. Therapeutic advances included optimization of androgen deprivation therapy, novel androgen receptor pathway inhibitors, chemotherapy, radiotherapy personalization, bone-targeted therapies, PSMA-directed radioligand therapy, and emerging immunotherapeutic approaches. Biomarker-driven strategies, including genomic classifiers and molecular signatures, showed potential for improving risk stratification and individualized treatment selection. Conclusion Prostate cancer is a biologically heterogeneous disease requiring integrated approaches that combine molecular understanding with clinical decision-making. Recent advances in precision oncology have expanded therapeutic options beyond conventional treatment paradigms, enabling more personalized management strategies. However, further research is required to improve representation of diverse populations, validate biomarkers across different ethnic groups, and optimize the clinical implementation of emerging targeted and immune-based therapies. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261435105.