Dr Calais on Refining Patient Selection for PSMA-Targeted Therapy in Prostate Cancer

“There is a continuum of PSMA expression levels, and there is also a lot of heterogeneity at the whole body level.”

Jeremie Calais, MD, PhD, a professor of nuclear medicine and theranostics at Gustave Roussy and Université Paris-Saclay, as well as an adjunct professor at UCLA Health, discussed how prostate-specific membrane antigen (PSMA) PET characteristics and complementary testing could refine patient selection for PSMA-targeted therapy in prostate cancer.

Calais explained that a positive or negative PSMA PET designation did not capture the full range of PSMA expression. Although clinical trials and regulatory decisions required a binary classification, he emphasized that clinicians could interpret scans in greater detail by examining expression levels and their distribution throughout the body.

He described PSMA expression as a continuum rather than an exclusively positive or negative finding. For example, one lesion could demonstrate pronounced uptake, while others simultaneously show little or no expression. Calais highlighted these differences as evidence of heterogeneity within an individual patient, which could be obscured by describing the entire scan as positive.

Calais also identified the volume of PSMA-positive disease as relevant to interpreting imaging findings. He distinguished between patients with extensive disease and those with a smaller volume, explaining that these presentations provided different information beyond whether the scan met a positivity threshold.

He characterized PSMA PET as a whole-body map of expression. This map could show uniformly positive or negative findings, patchy uptake, or substantial variation across lesions, he noted. Calais indicated that the combination of expression patterns and disease volume mattered when considering patient outcomes.

Beyond imaging, Calais discussed circulating tumor DNA (ctDNA) as another source of information relevant to treatment response. He noted that understanding of ctDNA features associated with better or poorer responses had expanded and described undetectable ctDNA levels as a favorable finding in prostate cancer.

He also highlighted fluorodeoxyglucose (FDG) PET, which he described as more widely used in Europe and Australia than in the United States. Calais explained that this complementary scan could identify aggressive, highly glycolytic lesions that PSMA PET does not reveal.