1411P Development and Validation of a Novel Six-Gene Signature to Accurately Risk Stratify Men with Early-Stage Prostate Cancer to Aid in Treatment Decision Making

Prostate cancer (PCa) is the second-most common non-cutaneous cancer in men with over 1.2 million men diagnosed worldwide annually. A large proportion of these men have indolent PCa and can safely defer treatment with active surveillance. Despite that, many patients are commonly treated with surgery (radical prostatectomy, RP) or radiation therapy, which are associated with a significant reduction in quality of life. In the past ten years, molecular signatures have been developed to assist clinicians in stratifying patients based on risk of aggressive PCa; while these have shown promise, there remains a significant opportunity for improving prognostic capacity. A panel of fourteen prognostic genes was identified from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) database. In an Irish cohort of men diagnosed with PCa and treated with RP (PCRC, n=426), cross-validated logistic regression analysis identified a molecular risk score (MRS) with strong prognostic performance to predict aggressive PCa, i.e. adverse pathology (AP) at RP or biochemical recurrence (BCR). The MRS was combined with the Cancer of the Prostate Risk Assessment (CAPRA) score to create a Molecular + CAPRA risk score (MCRS). We identified a six-gene signature with improved prognostic value over clinical features. The MRS and MCRS were validated in an independent Swedish cohort of men diagnosed with PCa and treated by RP (UPCA, n=203). The AUC of the signature for AP was 0.83 (MCRS) and 0.75 (MRS) versus 0.69 for EAU risk categories and 0.76 for CAPRA. The C-index for BCR was 0.83 (MCRS) and 0.74 (MRS) versus 0.69 for EAU risk categories and 0.77 for CAPRA. Furthermore, the six-gene signature added statistically significant (p < 0.0001) prognostic value to CAPRA and EAU. The six-gene prognostic signature has strong performance for both AP and BCR in an independent clinical validation study. It can assist clinicians and patients to determine whether active surveillance or active treatment is the most appropriate option based on their risk of aggressive disease and give confidence to men on their treatment choice.