Biomarkers for the Detection and Risk Stratification of Aggressive Prostate Cancer

Simple Summary Prostate cancer is a heterogeneous disease and a major cause of cancer deaths worldwide. The most widely used prostate cancer biomarker, prostate-specific antigen, lacks sensitivity and specificity in the diagnosis of malignant disease. Hence, novel tissue-based biomarkers have emerged for the detection and risk assessment of prostate cancer. Over the past years, liquid biopsy biomarkers introduced a new diagnostic concept to complement current tissue diagnosis strategies. Liquid biopsies non-invasively provide a characterization of heterogenous tumor profiles. Here, we highlight the most prominent tissue and liquid biopsy biomarkers for the detection and risk assessment of prostate cancer. Current strategies for the clinical management of prostate cancer are inadequate for a precise risk stratification between indolent and aggressive tumors. Recently developed tissue-based molecular biomarkers have refined the risk assessment of the disease. The characterization of tissue biopsy components and subsequent identification of relevant tissue-based molecular alterations have the potential to improve the clinical decision making and patient outcomes. However, tissue biopsies are invasive and spatially restricted due to tumor heterogeneity. Therefore, there is an urgent need for complementary diagnostic and prognostic options. Liquid biopsy approaches are minimally invasive with potential utility for the early detection, risk stratification, and monitoring of tumors. In this review, we focus on tissue and liquid biopsy biomarkers for early diagnosis and risk stratification of prostate cancer, including modifications on the genomic, epigenomic, transcriptomic, and proteomic levels. High-risk molecular alterations combined with orthogonal clinical parameters can improve the identification of aggressive tumors and increase patient survival.