Researchers have identified and validated a 12-gene androgen deprivation therapy (ADT) resistance signature that may predict which prostate cancer (PCa) patients are at elevated risk of adjuvant hormone treatment failure after radical prostatectomy, according to data scheduled to be presented at the 2016 Genitourinary Cancers Symposium.
R. Jeffrey Karnes, MD, of Mayo Clinic in Rochester, Minn., and colleagues analyzed gene expression profiles of 594 PCa patients who underwent radical prostatectomy (RP). The researchers split the patients into a training set (340 patients) and validation set (234 patients) and stratified them by the receipt of adjuvant ADT with 1 year (243 patients) or no adjuvant ADT (780 patients).
Dr. Karnes’ group performed a literature review of ADT resistance and neuroendocrine genes. Neuroendocrine PCa is inherently less sensitive or even resistant to ADT, the authors explained.
The researchers identified 1,557 candidate genes. Using logistic regression, they selected a 12-gene ADT resistance signature (ARS).
Among patients who received adjuvant ADT, metastases were significantly more likely to develop in patients with a high ARS score than those with a low ARS score. Kaplan-Meier analysis showed that the metastasis-free survival probability at 60 months was approximately 90% for patients with a low ARS and 80% for those with a high ARS. In contrast, among patients who did not receive adjuvant ADT, high versus low ARS scores did not predict development of metastases.