Integrating Molecular Profiling of Liquid Biopsy Samples with a Calculator Algorithm To Detect High risk Prostate Cancer.
Accurate identification of patients with early prostate cancer warranting treatment with curative intent remains problematic, with various approaches proposed to detect the presence of high risk disease. In this issue of European Urology, Van Neste et al [1] report findings for an approach in which two mRNA markers, homeobox genes HOXC6 and DLX1, are combined with traditional clinical risk factors used in the Prostate Cancer Prevention Trial (PRCPT) risk calculator. This group previously identified these genes and used them with TDRD1 in a urinary three gene panel that had higher accuracy than PCA3 or serum prostate specific antigen (PSA) [2] in predicting prostate cancer (Gleason score [2_TD$DIFF] 7) Two sequential multicentre clinical trials undertaken from 2009 to 2014 in The Netherlands included 519 men in a training cohort and 386 in a validation cohort. Expression levels ofHOXC6 and DLX1mRNA combined with serum PSA, PSA density, digital rectal examination (DRE) age, and family history yielded an overall area under the curve (AUC) of 0.90 (95% confidence interval [CI] 0.85 0.95) for the validation cohort (AUC 0.86 for the training cohort) The authors determined that serum PSA, family history, and age were no longer significant predictorswhenHOXC6 andDLX1 were included. Interestingly, addition of the commercial Progensa PCA3 previously promoted by this group did not improve predictability. The authors are to be congratulated for their approach in developing a well established calculator by incorporating molecular profiling in a clinician friendly manner for potential routine use. Because of the very promising findings reported here, it is expected that these markers
European urology