An ancillary analysis of the phase 3 PEACE-1 trial (NCT01957436) has identified prognostic biomarkers in de novo metastatic castration-sensitive prostate cancer (mCSPC) related to androgen receptor (AR) and neuroendocrine status, as well as alterations in tumor suppressor genes. The study, presented by Cedric Pobel, MD, at the Institut de Cancérologie Gustave Roussy, suggests that combining AR and neuroendocrine marker expressions can identify patient subgroups with different outcomes.
The research involved immunohistochemistry (IHC) assays with 10 markers targeting luminal and neuroendocrine features, and next-generation sequencing (NGS) on a restricted panel. The IHC assay defined five subgroups based on AR and neuroendocrine status: AR-high luminal, AR luminal weak, amphicrine, double negative, and neuroendocrine prostate cancer. Among 350 patients, those with AR-high luminal tumors had better prognoses, while neuroendocrine prostate cancer showed worse outcomes, primarily driven by neuroendocrine marker expression.
Impact of AR and Neuroendocrine Markers
Although no significant difference in radiographic progression-free survival (rPFS) or overall survival (OS) was noted among these subgroups, patients with neuroendocrine-positive markers exhibited worse outcomes, with an rPFS hazard ratio (HR) of 1.38 (P = 0.017) and an OS HR of 1.53 (P = 0.005). These findings suggest that both AR- and neuroendocrine-positive markers are negative prognostic indicators in mCSPC.
Role of Tumor Suppressor Gene Alterations
Further analysis revealed that alterations in tumor suppressor genes TP53, PTEN, and RB1 were prognostically significant. Patients with fewer than two alterations in these genes had a median OS of 5.4 years, compared to 2.2 years in those with two or more alterations (HR, 2.63). This indicates that alterations in these genes are associated with poorer outcomes in mCSPC.
Predictive Biomarkers for Abiraterone Benefit
The study also investigated whether AR or neuroendocrine biomarkers could predict response to abiraterone acetate plus prednisone. However, neither biomarker was found to be predictive of abiraterone benefit in mCSPC. According to Dr. Pobel, a predictive biomarker for abiraterone benefit in mCSPC remains undetermined.
These findings underscore the importance of phenotypic and genomic characterization in de novo mCSPC to predict outcomes with androgen deprivation therapy, with or without docetaxel, and with or without abiraterone acetate and prednisone. The study highlights the potential for personalized treatment strategies based on AR and neuroendocrine status, as well as tumor suppressor gene alterations.
