An ancillary study of the PEACE-1 phase 3 trial has identified phenotypic and genomic characteristics in de novo metastatic castration-sensitive prostate cancer (mCSPC) that may predict overall survival. The research, presented at the European Society for Medical Oncology (ESMO) Congress, analyzed data from patients treated with triplet therapy (castration, docetaxel, and abiraterone) to identify potential prognostic biomarkers.
Phenotypic Analysis
The phenotypic analysis, involving nearly 400 patients, categorized tumors based on the expression of androgen receptor (AR) and neuroendocrine markers. Five phenotypes were defined: AR low, AR high, neuroendocrine (AR negative, neuroendocrine marker positive), amphicrine (both AR and neuroendocrine marker positive), and double negative (both AR and neuroendocrine marker negative). While the double-negative and neuroendocrine phenotypes showed outlier survival rates, their small sample sizes limited interpretation. However, patients with AR-negative tumors demonstrated a clearly worse prognosis.
Further analysis of individual immunochemistry protein markers revealed that patients positive for synaptophysin or chromogranin A, both neuroendocrine markers, also had poorer outcomes. Surprisingly, almost 25% of patients had at least one neuroendocrine marker positive, and these patients collectively experienced a worse prognosis.
Cedric Pobel, MD, a medical oncologist and PhD student at Gustave Roussy Institute in Paris, France, noted that these phenotypic markers did not predict abiraterone response in the PEACE-1 trial, as all patients benefited from the addition of abiraterone to their treatment regimen.
Genomic Analysis
Next-generation sequencing (NGS) analysis revealed a similar number of genomic alterations compared to previously published data in mCSPC. Patients with alterations in at least one of the genes TP53, PTEN, or RB1 had a significantly worse prognosis, with overall survival reduced by half. However, this signature was only present in a small subset of patients (9 patients).
The study highlights the potential for using phenotypic and genomic data to refine prognostic assessments in mCSPC. While the identified markers did not predict abiraterone response in this trial, they may help identify patients who require more aggressive or alternative treatment strategies. Further research is needed to validate these findings and explore their clinical utility.
