Study Data Shows Potential of Gene Signatures to Predict Treatment Response in Patients With Recurrent Prostate Cancer

Author(s):

The research was aided by the Decipher Genomics Resource for Intelligent Discovery, which helped derive the gene signatures used during the analysis.

New data suggest that gene expression signatures may help advance understanding of the genomic drivers that impact patient response to treatment for recurrent prostate cancer, according to the authors of a study published in JCO Precision Oncology. The results from the 3-center, prospective phase 2 STREAM trial indicate the potential to use transcriptomic signatures to identify patients with recurrent prostate cancer who may benefit from more intensive salvage therapy, in addition to those who may need alternative methods of treatment such as chemotherapy.^1,2

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The findings were aided by data from Veracyte’s Decipher Genomics Resource for Intelligent Discovery (GRID) database, which includes over 100,000 whole-transcriptome profiles from patients with urologic cancers. It is available on a “research use only” basis.

“Using the Decipher GRID database, we found that men in the STREAM study with luminal differentiated genotypes had excellent outcomes, while those whose tumors had a basal, luminal proliferating genotype or other specific genomic characteristics such as PTEN loss had a higher risk of recurrence despite these therapies,” said senior author Andrew Armstrong, MD, ScM, professor of Medicine and director of Research at the Duke Cancer Institute Center for Prostate and Urologic Cancers, in a press release.

The goal of the trial was to evaluate the safety and efficacy of adding 6 months of enzalutamide to androgen deprivation therapy (ADT) and salvage radiotherapy in patients with rising prostate-specific antigen (PSA) following radical prostatectomy and radiotherapy (RT), according to the press release.

Of the 38 men enrolled in the trial, 31 had tissue with sufficient-quality RNA acceptable for genomic analysis. The longest 3-year progression free survival (PFS) was seen in those with luminal differentiated (LD) subtype tumors at 89%, compared with 19% in the luminal proliferating subtype.

Furthermore, men with signatures of PTEN loss (HR, 1.32; 95% CI, 1.07 to 1.64; P = .01) or homologous recombination deficiency (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.

“This study provides further evidence that the Decipher GRID database is a valuable tool to help researchers better understand the specific genomic signatures and factors that impact prostate cancer disease progression and individual responses to various treatment approaches,” said Elai Davicioni, PhD, medical director for urology at Veracyte.

Reference

1. BusinessWire. Veracyte announces that findings published in JCO Precision Oncology suggest potential of decipher GRID-derived gene signatures to predict treatment response in recurrent prostate cancer. News release. Accessed on August 23, 2023. Published on August 22, 2023. Accessible at https://www.businesswire.com/news/home/20230822976286/en.

2. Bitting R, Wu Y, Somarelli J, et al. Transcriptomic signatures associated with outcomes in recurrent prostate cancer treated with salvage radiation, androgen-deprivation therapy, and enzalutamide: correlative analysis of the STREAM trial. JCO Pres Onc. 2023;(7)e2300214. doi:10.1200/PO.23.00214