Jacob E. Berchuck, MD, shares next steps in research for a novel epigenomic liquid biopsy test for detecting PSMA in castration-resistant prostate cancer. 

Dr Berchuck on Next Steps for Evaluating a Novel Liquid Biopsy for PSMA in mCRPC

Jacob E. Berchuck, MD, assistant professor, Department of Hematology and Medical Oncology; medical oncologist, genitourinary cancers, Winship Cancer Institute, Emory University, shares potential next steps to evaluate and validate the correlation between a novel epigenomic liquid biopsy–predicted PSMA expression with the PSMA PET scans in metastatic castration-resistant prostate cancer (mCRPC).

In a study that investigated the use of a novel liquid biopsy assay to detect tumor PSMA expression, Berchuck notes that there are ongoing efforts to build on the work that was presented at the 

. Among patients with mCRPC undergoing PET scans in the study, he explains that additional plasma samples were collected to determine the correlation between a novel epigenomic liquid biopsy–predicted PSMA expression with the PSMA PET scan.

29 patients with mCRPC who underwent PSMA PET scan

 and provided a sample to use in the novel liquid biopsy assay. Patients were then screened for eligibility for lutetium Lu 177 vipivotide tetraxetan treatment.

Berchuck says he looks forward to furthering research regarding those who went on to receive lutetium Lu 177 vipivotide tetraxetan treatment. He explains that plasma samples are available from a larger prospective cohort taken at the time of lutetium Lu 177 vipivotide tetraxetan initiation. Based on the early data, cfDNA–predicted PSMA expression has shown a strong correlation with outcomes associated with lutetium Lu 177 vipivotide tetraxetan. He emphasizes that these results could indicate that cfDNA–predicted PSMA expression may be a potentially useful biomarker to help establish whether patients are more likely to have response to the treatment, and where to prioritize other prostate cancer therapies or clinical trials to improve patient outcomes.

Another area for next steps includes determining how tumors might evolve and develop resistance to lutetium Lu 177 vipivotide tetraxetan, Berchuck says. After collecting plasma samples from patients at the time of disease progression on lutetium Lu 177 vipivotide tetraxetan, he notes that using the epigenomic liquid biopsy assay may help identify possible treatment resistance.

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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 

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 

 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.

Jacob E. Berchuck, MD, discusses the use of a novel epigenomic liquid biopsy platform to noninvasively detect PSMA expression in mCRPC.

Jacob E. Berchuck, MD

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Dr Berchuck on Next Steps for Evaluating a Novel Liquid Biopsy for PSMA in mCRPC

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