Molecular correlates of intermediate- and high-risk localized prostate cancer

Clinicopathologic parameters, including Gleason score, remain the most validated prognostic factors for patients diagnosed with localized prostate cancer (PCa). However, patients of the same risk groups have exhibited heterogeneity of disease outcomes. To improve risk classification, multiple molecular risk classifiers have been developed, which were designed to inform beyond existing clinicopathologic classifiers. Alterations affecting tumor suppressors and oncogenes, such as PTEN, MYC, BRCA2, and TP53, which have been long associated with aggressive PCa, demonstrated grade-dependent frequency of alterations in localized PCas. In addition to these genetic hallmarks, several RNA-based commercial tests have been recently developed to help identify men who would benefit from earlier interventions. Large genomic studies also correlate germline genetic alterations and epigenetic features with adverse outcomes, further strengthening the link between the risk of metastasis and a stepwise accumulation of driver molecular lesions.