Clinical Utility of Novel Biomarkers in the Era of Active Surveillance of Prostate Cancer

Kim, Jeong Hyun

Abstract

Active surveillance (AS) is an alternative to initial radical treatment for men with low-risk localized prostate cancer (PCa). Current AS criteria for selection and follow-up incorrectly exclude some patients eligible for AS and misclassify some who actually harbour significant disease. It is crucial what will serve as the best parameter to correctly identify tumors that progress to a more aggressive phenotype so as not to miss the window of curability. There is an unmet need for a noninvasive biomarker test that can provide a higher degree of specificity for detecting aggressive disease than currently available clinical tools. Several biomarkers are now being actively investigated as novel tools to improve PCa risk assessments. Prostate-specific antigen (PSA) isoform [-2]proPSA and its derivatives, percentage of [-2]proPSA to free PSA (%[-2]proPSA) and Prostate Health Index (PHI), have higher accuracy than the currently used PSA and other PSA derivatives for predicting PCa detection and aggressiveness. In the AS program, %[-2]proPSA and PHI showed improved predictive value for an unfavorable biopsy conversion at annual surveillance biopsy. Although prostate cancer antigen 3 (PCA3) was limited in predicting aggressive cancer, PCA3 and TMPRSS2:ERG also had additional independent predictive value for predicting PCa. However, the roles of PCA3 and TMPRSS2:ERG in risk assessment during AS need to be tested in additional multi-institutional studies. Tissue biomarkers also showed promising ability to predict disease progression. Although the biopsy-based tissue biomarkers provide additional prognostic information over existing clinical tools, further validation studies are also needed to provide robust evidence.