The Role of PSMA PET Parameters as Biomarkers for Response to PSMA-Targeted Radiopharmaceutical Therapy

Prostate-specific membrane antigen (PSMA) PET is a well-established imaging tool for the evaluation of primary and recurrent prostate cancer (PCa). ¹⁷⁷Lu PSMA-targeted radiopharmaceutical therapy (RPT) enables direct delivery of β-radiation to PSMA-expressing PCa cells while minimizing damage to normal tissue. As PSMA RPT becomes more widely used, there is growing interest in evaluating the predictive and prognostic role of PSMA PET parameters to enable better patient selection and effectively monitor treatment response. The purpose of this paper is to review the role of PSMA PET parameters as biomarkers for PSMA RPT. Quantitative parameters on baseline PSMA PET can serve as prognostic biomarkers for overall survival and predictive biomarkers for prostate-specific antigen response. Alongside lesion-based assessments, changes in whole-body quantitative parameters from baseline to interim or end-of-treatment PSMA PET are prognostic for overall survival and progression-free survival in patients undergoing PSMA RPT. Changes in quantitative, whole-body PSMA PET parameters may better reflect changes in PCa following systemic therapy compared with individual lesion-based assessments. Further research is necessary in larger, prospective trials to characterize the role of PSMA PET parameters as prognostic biomarkers for progression-free survival and overall survival in metastatic castration-resistant PCa patients undergoing PSMA RPT.