Transcriptome profiling of prostatic tumours from ENACT trial patients with or without enzalutamide

Area of Science:

• Genomics
• Oncology
• Immunology

Background:

• The ENACT trial (NCT02799745) investigated enzalutamide plus active surveillance (AS) versus AS alone for low- or intermediate-risk prostate cancer.
• Understanding longitudinal transcriptomic changes is crucial for evaluating treatment effects and disease progression.

Purpose of the Study:

• To analyze longitudinal transcriptomic alterations in patients from the ENACT trial.
• To correlate gene expression changes with clinical and biological features.

Main Methods:

• Gene-expression profiling using the Decipher Genomic Resource for Intelligent Discovery (GRID) platform on 131 patient samples.
• Analysis of pre-defined GRID signatures for associations with immune activity, treatment sensitivity, metastatic risk, and molecular subtypes.
• Statistical analysis using Cox models, regression, and linear mixed-effects models for longitudinal changes.

Main Results:

• Enzalutamide plus AS treatment led to significant Year 1 transcriptomic changes, including downregulated androgen-receptor signaling and immune-suppressor signatures.
• Upregulation of immune-activated and basal-like markers was observed.
• Most transcriptomic alterations, including immune changes, were transient, reverting by Year 2 after treatment cessation.

Conclusions:

• This analysis reveals transcriptomic shifts during active surveillance and enzalutamide treatment in prostate cancer.
• Findings provide insights into molecular disease progression and the transient effects of enzalutamide.
• Observed immune modulation suggests potential for exploring novel immunotherapy strategies.