Both serum-based and urine-based secondary biomarkers have been identified that may augment the poor specificity of PSA screening to improve detection of clinically significant prostate cancer while limiting biopsy need among men who have not undergone a prior prostate biopsy.1 While multiple biomarkers meet thresholds to be considered for use prior to initial prostate biopsy,2 few studies have been completed that evaluate the performance of combined or sequenced use of noninvasive markers. In a multisite cohort, Eyrich et al3 assessed the value of a combined blood-based (prostate health index, phi) and urine-based (TMPRSS2:ERG + PCA3) testing approach in detecting clinically significant (grade group 2 or higher) prostate cancer among biopsy-naive men. After developing a combined testing approach in a training cohort (n = 512), they applied the locked testing approach in a validation cohort (n = 561) and found that the combination of these markers outperformed PCA-T2:ERG alone in 3 tested models. These data therefore suggest that combination approaches may improve the identification of men who are at increased risk of clinically significant prostate cancer and who would benefit from prostate biopsy. The study is, however, limited by a lack of MRI data and reliance on systematic biopsy templates. MRI, in particular, is firmly entrenched as a valuable test before initial prostate biopsy,2 highlighting the need for future studies that combine (or sequence) the use of MRI with serum and/or urine biomarkers to best select men for prostate biopsy.
Ellis et al. (Sun,) studied this question.