Utilization of biopsy-based genomic classifier to predict distant metastasis after definitive radiation and short-course ADT for intermediate and high-risk prostate cancer

Abstract

BACKGROUND: We examined the ability of a biopsy-based 22-marker genomic classifier (GC) to predict for distant metastases after radiation and a median of 6 months of androgen deprivation therapy (ADT). METHODS: We studied 100 patients with intermediate-risk (55%) and high-risk (45%) prostate cancer who received definitive radiation plus a median of 6 months of ADT (range 3-39 months) from 2001-2013 at a single center and had available biopsy tissue. Six to ten 4 micron sections of the needle biopsy core with the highest Gleason score and percentage of tumor involvement were macrodissected for RNA extraction. GC scores (range, 0.04-0.92) were determined. The primary end point of the study was time to distant metastasis. Median follow-up was 5.1 years. There were 18 metastases during the study period. RESULTS: On univariable analysis (UVA), each 0.1 unit increase in GC score was significantly associated with time to distant metastasis (hazard ratio: 1.40 (1.10-1.84), P = 0.006) and remained significant after adjusting for clinical variables on multivariable analysis (MVA) (adjusted hazard ratio: 1.36 (1.04-1.83), P = 0.024). The c-index for 5-year distant metastasis was 0.45 (95% confidence interval: 0.27-0.64) for Cancer of the Prostate Risk Assessment score, 0.63 (0.40-0.78) for National Comprehensive Cancer Network (NCCN) risk groups, and 0.76 (0.57-0.89) for the GC score. Using pre-specified GC risk categories, the cumulative incidence of metastasis for GC40.6 reached 20% at 5 years after radiation (P = 0.02). CONCLUSIONS: We believe this is the first demonstration of the ability of the biopsy-based GC score to predict for distant metastases after definitive radiation and ADT for intermediate-And high-risk prostate cancer. Patients with the highest GC risk (GC40.6) had high rates of metastasis despite multi-modal therapy suggesting that they could potentially be candidates for treatment intensification and/or enrollment in clinical trials of novel therapy.