Dr Berchuck on Detecting PSMA Expression With a Novel Epigenomic Liquid Biopsy in mCRPC

Jacob E. Berchuck, MD, assistant professor, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, discusses the ability of a novel epigenomic liquid biopsy platform to noninvasively detect prostate-specific maturation antigen (PSMA) expression in metastatic castration-resistant prostate cancer (mCRPC), according to results from a study presented at the 2024 ESMO Congress.

A recent study investigated the use of a novel liquid biopsy assay to predict tumor PSMA expression in a cohort of 29 men with mCRPC who underwent PSMA PET scan with the intent of screening for lutetium Lu 177 vipivotide tetraxetan (Pluvicto) treatment eligibility. Plasma samples were collected around the time of these scans to evaluate if a blood-based assessment could predict tumor PSMA expression.

The study utilized a liquid biopsy assay to analyze the epigenomic signal at the FOLH1 gene, which encodes PSMA, in cell-free DNA (cfDNA) from plasma, Berchuck explains. The goal was to determine how well this blood-based signal correlated with tumor PSMA expression seen on PET scans, specifically measuring the standardized uptake value (SUV) mean, he details.

The initial cohort analysis revealed a strong correlation of approximately 0.7 between cfDNA-predicted PSMA expression and PSMA expression as determined by PSMA PET scan, Berchuck reports. The research team further validated these findings by building a machine learning model, which was then applied to an independent cohort, he says. In this secondary analysis, the correlation strengthened to 0.8 (80%) between cfDNA-predicted PSMA expression and PET-detected PSMA expression, Berchuck states.

These findings suggest that liquid biopsy platforms could serve as non-invasive tools for assessing tumor expression of therapeutic targets like PSMA, Berchuck emphasizes. He adds that this assay may provide a convenient surrogate to PSMA PET scans for patient selection in therapies involving radiopharmaceuticals like lutetium Lu 177 vipivotide tetraxetan. This, in turn, could improve screening and monitoring processes in mCRPC, Berchuck concludes.