Phenotypic Biomarker Characterization in de Novo Metastatic Prostate Cancer

The phenotype assessed by immunohistochemistry (IHC) analysis is a strong prognostic biomarker in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with androgen-deprivation therapy (ADT), with or without docetaxel and with or without acetate/prednisone (AAP).

The researchers, led by Cedric Pobel, MD, PhD, aimed to identify prognostic and predictive biomarkers associated with radiographic progression-free survival (PFS) and overall survival (OS) in de novo mCSPC patients as an ancillary study of the PEACE-1 phase 3 trial.

They collected 595 paraffin-embedded samples from participants of the randomized PEACE-1 trial for IHC analysis. This analysis included validated antibodies staining luminal components, neuroendocrine (NE) features, tumor suppressors, Ki67, and ERG. Cox models were fitted with each IHC marker adjusted for age, tumor burden, Gleason score, Eastern Cooperative Oncology Group score, and previous treatments received.

Five phenotype subgroups were defined using luminal and NE status. Among the 350 patients with an assessable phenotype, 150 (42.9%) were AR-high luminal, 97 (27.7%) AR luminal weak, 95 (27.1%) amphicrine, three (0.8%) double negative, and five (14%) neuroendocrine prostate cancer (NEPC).

No significant difference in rPFS or OS between these five subgroups was observed, but there was a trend from AR-high luminal (better prognosis) to NEPC (worse prognosis), mainly driven by NE status. Patients with at least one NE-positive marker had a shorter rPFS (hazard ratio [HR], 1.38; 95% CI, 1.06-1.81; P=.017) and OS (HR, 1.53; 95% CI, 1.14-2.06; P=.005). Patients with ERG-positive marker had a longer rPFS (HR, 0.71; 95% CI, 0.53-0.94; P=.019). None of the biomarkers were found to be predictive of response to AAP.