Predictive Value of PSMA Protein Expression of Response to Lu-177 PSMA Therapy in Prostate Cancer

A study presented during the 2021 ASCO Annual Meeting evaluated whether PSMA protein expression was a reliable predictor of response to Lu-177 PSMA therapy in patients with castration-resistant prostate cancer (CRPC).

Nineteen patients with multiple metastases at multiple sites underwent metastatic lesion biopsy, Ga-68 PSMA PET imaging, and subsequent treatment with three cycles of Lu-177 PSMA over a five-year period. PSMA protein expression was assessed in the biopsy specimen using a monoclonal anti-PSMA antibody. The researchers evaluated imaging per the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) criteria.

Twelve patients had biopsy specimens ready for staining, and PSMA expression was found to be associated with enhancement (SUV_max) of the biopsy site on Ga-68 PSMA PET imaging (r_s = 0.63). Nine patients underwent imaging again following therapy, and five had a lesion-specific response at the site of the biopsy. In univariable analysis, PSMA expression on immunohistochemistry did not forecast lesion-specific response. Three of the five men with a lesion-specific response had overall progression per the PERCIST criteria, and lesion-specific response did not correlate with overall progression.

“In patients with multiple metastases, PSMA protein expression from a single site biopsy was not predictive of site-specific Lu-177 PSMA response based on PERCIST. Additional studies are necessary to further interrogate the clinical consequence of PSMA expression heterogeneity in metastatic sites as well as the mechanisms underpinning resistance to Lu-177 PSMA in patients with CRPC,” the study authors concluded.