Genomic analysis in active surveillance: predicting high-risk disease using tissue biomarkers

For patients newly diagnosed with prostate cancer, the most significant question is whether the 'truly malignant' disease has been identified. This review will provide an overview of current prostate cancer genomic and biomarker discovery - validation strategies geared towards identifying aggressive, clinically significant disease at the time of diagnosis.

Based on recent findings the prostate cancer aggressive disease phenotype develops as a result of mutations (TP53, PTEN), structural events (TMPRSS2-ETS), epigenetic changes (EZH2, DAB2IP, histone alteration), and transcriptional modifications (SChLAP, PCAT-1). Copy number variability and dysregulation of specific pathways including androgen receptor signaling, PTEN/PAKT and TGF-β continue to play an important role in invasion and metastasis.

Given the current challenges for applying prostate cancer genomics to clinical management, this review will incorporate some of the current novel genomic approaches and techniques including systems-based precise pathology platforms, and the role of fluid-based assays, notably, exosomes and circulating tumor cells (liquid biopsy), as tools for future diagnostic-treatment algorithms.