Circulating biomarkers for discriminating indolent from aggressive disease in prostate cancer active surveillance

To review research on the use of circulating biomarkers to predict unfavorable tumor pathology in the setting of active surveillance, or in clinical contexts that are informative for active surveillance, such as men with low-risk prostate cancer evaluated for upgrading or upstaging at surgery.

Biomarkers have been evaluated in serum, plasma, urine, and expressed prostatic secretions. Only a small number of biomarkers have been evaluated in multiple studies: %free prostate-specific antigen (PSA), PSA velocity, PSA doubling time, proPSA, PCA3, TMPRSS2-ERG. Single studies with relevance to active surveillance have evaluated microRNAs, circulating tumor cells, and exosomes. The most consistent significant associations with unfavorable tumor pathology have been with %free PSA. Associations with [-2]proPSA and Prostate Health Index have also been consistent; however, three of four studies come from the same active surveillance patient cohort.

Circulating biomarkers represent a promising approach to identify men with apparently low-risk biopsy pathology, but who harbor potentially aggressive tumors unsuitable for active surveillance. Research is still at an early stage; existing biomarkers need rigorous validation with consistent methodology, and additional biomarkers need to be evaluated. Successful clinical translation would reduce the frequency of surveillance biopsies, and may enhance acceptance of active surveillance.