Androgen receptor activity in biopsy specimens at initial diagnosis of prostate cancer and correlation with outcomes and treatment response.

• DOI: 10.1200/jco.2025.43.5_suppl.409
• Publication Date: 2025-02-18T14:32:12Z
• Authors: Nicole Handa; Mohammed Alshalalfa; Yangyang Hao; Hyunnam Monica Ryu; James A. Proudfoot; Elai Davicioni; Matthew R. Cooper...; Alejandro Berlin; Paul L. Nguyen; Daniel Eidelberg ...; Ridwan Alam; Ashley Ross; Edward M. Schaeffer

409 Background: Androgen receptor activity (AR-A) has been described after radical prostatectomy (RP) and metastatic castration-sensitive prostate cancer (mCSPC). In RP specimens low AR-A is associated with basal subtypes, decreased DNA repair increased immune activity. mCSPC, poor overall survival (OS) time to progression CRPC. However, not well characterized in localized disease at initial diagnosis. Here we sought assess signatures biopsy samples from patients across the risk continuum correlations between outcomes. Methods: We analyzed 150,162 tested (2016-2024) Decipher genomic classifier (Veracyte, Inc. San Diego, CA). Transcriptome-wide expression data clinical factors were retrieved GRID (NCT02609269). Patients high as defined by Spratt et al 2019 compared using Chi-square tests. Clinical pathologic outcomes for specific cohorts sample population Cox regression. Results: Overall, 11,752 (7.8%) had expression. 9.8% of > 70 years age 7.6% <70 (p<0.0001). Low was enriched prognostic such very (p<0.0001), Grade Group (GG) 5 (p<0.0001) NCCN The same differences present when looking only a PSA <4 ng/mL. Like samples, positively correlated intact negatively PORTOS infiltration scores (all p<0.001). 4 independent retrospective cohorts. cohort 1, intermediate (n=647), adverse pathology (p <0.05). 2, treated radiation therapy (RT) (n=121), biochemical failure (p<0.05). 3, (n=405), OS (p<0.05) all metastasis RT androgen deprivation (ADT). Finally, 4, RT+ADT (n=100), (p<0.01). Conclusions: large specimens, age, score, risk, GG5 disease. Subpopulation analyses suggest that portends prognosis. Given scores, clinicians should consider post-operative novel trials PARP inhibitors these patients.