Liquid biomarkers in active surveillance

Purpose In the past two decades, new biomarkers for prostate cancer detection and risk prediction have become available for clinical use. While tissue-based gene expression assays offer molecular risk assessment after diagnoses, several serum- and urine-based 'liquid' biomarkers are available for the pre-biopsy setting which may also play a role for active surveillance (AS). Methods The medical literature was queried utilizing PubMed (pubmed.ncbi.nlm.nih.gov) for all relevant original publications describing prostate cancer biomarkers that can be identified in the blood, urine, or semen. Referenced studies must have defined patient inclusion criteria and descriptions of the biomarkers. Included studies investigated the utility of liquid biomarkers for selection or monitoring of men with prostate cancer for active surveillance. Results PSA is the most common and readily available biomarker for prostate cancer diagnosis and treatment. Contemporary AS guidelines consider diagnostic PSA level in addition to other clinical factors when selecting men for this approach, with most recommending that initial PSA should be under 10 ng/ml. Serum PSA changes are associated with outcomes on AS but are not adequately sensitive so drive men to secondary treatment in isolation. PSA derivates including the Prostate Health Index (phi) and the 4K Score can predict higher grade cancer and may help tailor repeat prostate biopsy strategies, but further data are needed prior to routine clinic use. Several urine-based biomarkers including PCA3 and TMPRSS2:ERG levels have also been studied in the AS setting. Conclusions Multiple serum- and urine-based liquid biomarkers are available for use in men with prostate cancer. For AS, serum PSA is utilized in part for patient selection as well as to monitor disease over time. Models that incorporate PSA kinetics with other clinical characteristics may help tailor surveillance strategies to reduce disease burden and health care costs over time. Several novel liquid biomarkers demonstrate promise and may eventually have applications for prostate cancer surveillance as well.