Development and Validation of a Prostate Cancer Genomic Signature that Predicts Early ADT Treatment Response...

Area of Science:

• Genomics and Precision Oncology
• Prostate Cancer Research
• Molecular Signatures in Cancer Therapy

Background:

• No established genomic signature exists to predict response to adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients after radical prostatectomy.
• Identifying patients who will benefit from ADT is crucial for optimizing treatment and minimizing side effects.

Purpose of the Study:

• To develop and validate a gene expression signature (ADT-RS) for predicting response to postoperative ADT in high-risk prostate cancer.
• To identify patients most likely to benefit from adjuvant ADT after radical prostatectomy.

Main Methods:

• A training set of 284 radical prostatectomy patients was used to identify the ADT Response Signature (ADT-RS) from neuroendocrine and AR signaling genes.
• The signature was validated in three independent cohorts (n=232, n=435, n=612) using postoperative metastasis as the primary endpoint.
• Propensity score matching was employed to balance treatment groups.

Main Results:

• Increased ADT-RS scores were associated with reduced metastasis risk specifically in patients receiving adjuvant ADT (a-ADT).
• The ADT-RS by ADT treatment interaction was significant in multivariable analyses of validation sets.
• In a matched validation set, high ADT-RS patients showed significantly lower 10-year metastasis rates with a-ADT compared to no ADT (9.4% vs. 29.2%).

Conclusions:

• Patients with high ADT-RS scores demonstrate a significant benefit from adjuvant ADT after radical prostatectomy.
• The ADT-RS, combined with prognostic factors, can identify ADT-responsive tumors, enabling personalized androgen blockade strategies.
• This gene signature holds promise for predicting patient response to early ADT following prostate cancer surgery.