The assessment of the risk of biochemical recurrence (BCR) is critical in the management of males with prostate cancer (PC). Over the past decades, a comprehensive effort has been focusing on improving risk stratification; a variety of models have been constructed using PC‑associated pathological features and molecular alterations occurring at the genome, protein and RNA level. Alterations in RNA expression (lncRNA, miRNA and mRNA) constitute the largest proportion of the biomarkers of BCR. In this article, we systemically review RNA‑based BCR biomarkers reported in PubMed according to the PRISMA guidelines. Individual miRNAs, mRNAs, lncRNAs and multigene panels, including the commercially available signatures, Oncotype DX and Prolaris, will be discussed; details related to cohort size, hazard ratio and 95% confidence intervals will be provided. Mechanistically, these individual biomarkers affect multiple pathways critical to tumorigenesis and progression, including epithelial‑mesenchymal transition (EMT), phosphatase and tensin homolog (PTEN), Wnt, growth factor receptor, cell proliferation, immune checkpoints and others. This variety in the mechanisms involved not only validates their associations with BCR, but also highlights the need for the coverage of multiple pathways in order to effectively stratify the risk of BCR. Updates of novel biomarkers and their mechanistic insights are considered, which suggests new avenues to pursue in the prediction of BCR. Additionally, the management of patients with BCR and the potential utility of the stratification of the risk of BCR in salvage treatment decision making for these patients are briefly covered. Limitations will also be discussed.

International journal of oncology. 2019 Oct 04 [Epub ahead of print]

Xiaozeng Lin, Anil Kapoor, Yan Gu, Mathilda Jing Chow, Hui Xu, Pierre Major, Damu Tang

Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada., The Research Institute of St. Joe’s Hamilton, St. Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada., Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China., Division of Medical Oncology, Department of Oncology, McMaster University, Hamilton, ON L8V 5C2, Canada.