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• W4385972783 abstract "PURPOSE Men with rising prostate-specific antigen (PSA) after radical prostatectomy (RP) may progress despite radiation and androgen-deprivation therapy (ADT). Tissue-based transcriptomic signatures can identify who may benefit from a more aggressive systemic approach. METHODS We performed a retrospective analysis of a prospective phase II multicenter trial of enzalutamide, ADT, and salvage radiotherapy in men with rising PSA after RP. Tumor tissue was analyzed using the Decipher platform for gene expression, including a novel prostate subtyping classifier, PTEN loss, homologous recombination deficiency (HRD), and ADT response. Cox models were used to associate signature scores with progression-free survival (PFS). RESULTS Of the 38 men enrolled, 31 had tissue with sufficient-quality RNA for genomic analysis. Luminal differentiated (LD) subtype tumors had the longest 3-year PFS at 89% compared with 19% in the luminal proliferating subtype. Men with signatures of PTEN loss (hazard ratio [HR], 1.32; 95% CI, 1.07 to 1.64; P = .01) or HRD (HR, 1.21; 95% CI, 1.05 to 1.39; P = .009) had worse PFS, while those with higher ADT response signature scores (HR, 0.75; 95% CI, 0.61 to 0.94; P = .01) were associated with improved PFS. Analysis of these signatures in a large cohort (n = 5,330) of RP samples from patients with biochemical recurrence found that these signatures provide complementary information related to outcomes with salvage radiation. CONCLUSION Despite aggressive systemic therapy with salvage radiation, nearly 50% of high-risk men relapse within 3 years. We show that LD and higher ADT sensitivity tumors had favorable outcomes. Those with a luminal proliferating subtype, PTEN loss, and/or HRD signatures had poor outcomes despite ADT/radiation and enzalutamide and may benefit from alternative approaches." @default.
• W4385972783 created "2023-08-19" @default.
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• W4385972783 date "2023-08-01" @default.
• W4385972783 modified "2023-10-14" @default.
• W4385972783 title "Transcriptomic Signatures Associated With Outcomes in Recurrent Prostate Cancer Treated With Salvage Radiation, Androgen-Deprivation Therapy, and Enzalutamide: Correlative Analysis of the STREAM Trial" @default.
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• W4385972783 doi "https://doi.org/10.1200/po.23.00214" @default.
• W4385972783 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37595184" @default.
• W4385972783 hasPublicationYear "2023" @default.
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