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It is important for clinicians involved in the care of patients with prostate cancer to take note of novel insights in the role of the breast cancer type susceptibility protein (BRCA) genes in prostate cancer initiation and progression. The BRCA genes play an important role in DNA damage repair, particularly in the error-free repair of double-stranded DNA breaks. There are both clinical as therapeutic consequences. Patients that develop prostate cancer and have a somatic or germline BRCA2 mutation, show a worse initial staging and a more aggressive clinical course of their disease. In the metastatic castration-resistant setting, poly (ADP-ribose) polymerase (PARP) inhibitors have recently established their place in the therapeutic landscape. The first registration of a PARP inhibitor is expected in mid-2020. Knowledge of the BRCA germline mutation status can have important consequences for both the patient and his family. DNA testing will be used more frequently for optimal risk assessment and to individualize treatment of patients with localized as metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: In 2021, the identification of effective biomarkers became a major focus of prostate cancer (PCa) in order to improve outcomes and select potentially responsive patients. The aim of this contribution is to review the main 2021 novelties in prognostic and therapeutic markers in PCa, with special reference to PCa grading, aggressive variant PCa and molecular markers predicting significant disease or response to therapy. The 2021 novelties in prognostic and therapeutic tissue markers in patients with prostate cancer (PCa) can be subdivided into two major groups. The first group is related to prognostic markers based on morphological and immunohistochemical evaluations. The novelties in this group can then be subdivided into two subgroups, one involving morphologic evaluation only, i.e., PCa grading, and the other involving both morphologic and immunohistochemical evaluations, i.e., aggressive variant PCa (AVPCa). Grading concerns androgen-dependent PCa, while AVPCa represents a late phase in its natural history, when it becomes androgen-independent. The novelties of the other major group are related to molecular markers predicting significant disease or response to therapy. This group mainly includes novelties in the molecular evaluation of PCa in tissue material and liquid biopsies. [ABSTRACT FROM AUTHOR]