Screening for Prostate Cancer: Beyond Prostate-specific Antigen

Abstract Introduction: Prostate-specific antigen (PSA) testing has been the cornerstone of prostate cancer (PC) screening for decades. However, its limited specificity and potential for overdiagnosis have prompted the search for more accurate and personalized screening strategies. With advances in biomarkers and imaging technologies, several novel approaches have emerged. This review aims to summarize the current evidence on screening tools beyond PSA and assess their clinical potential. Materials and Methods: A structured literature search was conducted in May 2024 using PubMed (Medline) and Google Scholar. Search terms included “Prostate Cancer,” “Screening,” “Biomarkers,” “Multiparametric MRI,” “4Kscore,” “PHI,” “Molecular Diagnostics,” and “PSMA PET,” combined using Boolean operators. English-language articles published within the last 10 years were included, prioritizing systematic reviews, meta-analyses, randomized controlled trials, and large prospective studies. Reference lists were screened to identify additional relevant literature. Selected studies were grouped into laboratory- and imaging-based screening modalities and critically reviewed. Results: Several emerging tools show potential to enhance PC screening. Blood-based tests such as the 4Kscore, PHI, and Stockholm3 combine PSA with additional biomarkers and clinical factors to improve risk stratification and reduce unnecessary biopsies. Urine-based assays offer noninvasive alternatives with better specificity. Novel molecular markers including microRNAs, long noncoding RNAs, and single-nucleotide polymorphisms are under investigation. Imaging-based methods such as multiparametric MRI, micro-ultrasound, contrast-enhanced ultrasound, and PSMA positron emission tomography/computed tomography offer improved lesion detection and risk assessment. Conclusions: While promising, these approaches require further validation through large-scale trials. Integrating biomarkers and imaging may enable more precise, personalized, and safer screening for PC.