Utilization of Biopsy-based Genomic Classifier to Predict Distant Metastasis - Commentary from the Associate Editor of PCAN

Molecular risk tools are being increasingly utilized in men with localized prostate cancer to help in clinical decision making around the need for surgery or radiation vs. active surveillance, and for the need for salvage radiation after surgery.  The Decipher Genomic Classifier has recently been demonstrated to predict distant metastases in men undergoing radical prostatectomy, using biopsy or surgical tissue, and may provide a greater level of prognostic discrimination than current NCCN or CAPRA risk groups.  This combined clinical-genomic classifier may thus permit clinical trials testing the incorporation of this test into treatment algorithms for treatment intensification such as salvage radiation and hormonal therapy for high risk men with a rising post-operative PSA, or de-intensification, such as avoiding radiation altogether in low risk men with undetectable post-operative PSA values.

Nguyen et al. report on the novel utility of the Decipher classifier in a cohort of 100 men undergoing radiation and ADT at Dana Farber.  These men were largely intermediate and high risk (55 and 45, respectively), and most men were treated with 6 months of ADT prior to, during, and following IMRT at a dose of 72 Gy.  About 31% received 1-3 years of ADT.  The authors found that of these 100 men, the genomic classifier was strongly and independently associated with distant metastases, with a 40% increase in risk per 0.1 unit increase in the score, while neither CAPRA risk nor NCCN risk were prognostic in this cohort of intermediate/high risk men. The Decipher risk remained associated with metastasis prediction after adjusting for stage, grade, percent cores positive, duration of ADT, and year of treatment and remained the strongest predictor with a c-index of 0.76 for 5 year metastasis risk, as compared to 0.63 for NCCN clinical risk and 0.45 for CAPRA risk. 

Together, these data support a combined use of clinical risk and genomic risk assessment in the management of men with localized prostate cancer, and illustrate the shortcomings of clinical risk groups, especially within the intermediate and high risk groups. Some men with intermediate risk PC have a low genomic risk and do well, while others behave more like high risk disease.  Combined with existing RP data around metastasis risk, these data continue to support clinical trials of using the Decipher assay to investigate intensifying therapy for high risk men, such as with novel AR inhibitors or novel systemic approaches, in combination with radiation and ADT.  These studies also support potentially de-escalating care in low risk men. Before making such treatment decisions, however, prospective studies testing these biomarker-driven clinical algorithms are needed in defined settings.  I suspect that future treatment algorithms will be improved upon through the use of such genomic risk biomarkers and lead to better outcomes for our patients based on their personalized risk.

Written by: Andrew Armstrong, MD, ScM, FACP, USA. Dr. Armstrong is Associate Professor of Medicine, Surgery, Pharmacology and Cancer Biology and Associate Director of the Duke Cancer Institute Genitourinary Clinical Research Program. He is a medical oncologist and internationally recognized expert in experimental therapeutics and biomarker development in genitourinary cancers, particularly in prostate cancer.

Read the PCAN Full Text Article: Utilization of Biopsy-Based Genomic Classifier to Predict Distant Metastasis after Definitive Radiation and Short-Course ADT for Intermediate and High-Risk Prostate Cancer