Validation of the Decipher Test for Predicting Distant Metastatic Recurrence in Men with High-risk Nonmetastatic Prostate Cancer 10 Years After Surgery

Background: Decipher is a genomic classifier designed to predict the development of distant metastases after surgical treatment of prostate cancer (PC). Its long-term prognostic role in a highrisk PC population has not been investigated previously. Objective: To determine the prognostic role of the Decipher genomic classifier in two high-risk PC case-control studies. Design, setting, and participants: Patients who developed distant metastases after surgery for high-risk, nonmetastatic PC in a European tertiary referral center from 1991 to 2011 were matched to patients not developing distant metastases (n = 54). A validation study (n = 298) was performed using a similar US case-control cohort. Formalin-fixed, paraffin-embedded tissue blocks from the index PC lesion were used for RNA extraction and gene expression analysis. Outcome measurements and statistical analysis: The outcome investigated was the development of distant metastasis within 10-yr follow-up. Multivariable logistic regression analysis was performed, with statistical significance considered at p < 0.05. Results and limitations: In both the European and US case-control studies, the median Decipher scores were higher in the population that developed metastases. In the multivariable analysis, each 10% increase in Decipher score translated to an increase in the risk of distant metastases within 10-yr follow- up, with an odds ratio of 1.53 (95% confidence interval [CI] 1.06–2.22; p = 0.025) and 1.58 (95% CI 1.31–1.92; p < 0.001) for the European and US cohorts, respectively. Median follow-up for the European cohort was 12 yr (interquartile range 8–12). The study limitation is the small size of the European cohort. Conclusions: Our study validates Decipher as a predictor for metastatic recurrence even in patients with high-risk, nonmetastatic PC within 10-yr follow-up. Patient summary: Decipher is a test based on gene expression profiles in primary tumors in prostate cancer. It has already been proven to predict cancer recurrence after surgery, but this has not yet been shown for patients with high-risk prostate cancer. This is the first study confirming that Decipher predicts a patient’s risk of developing cancer recurrence after surgery for high-risk prostate cancer.status: publishe