Baseline PSMA PET/CT Biomarkers for Patient Selection in [177Lu]Lu-PSMA Radioligand Therapy: Clinical Promise, Methodological Heterogeneity and Future Standardization

PSMA PET/CT imaging biomarkers are increasingly investigated as predictors of response and survival outcomes following [177Lu]Lu-PSMA radioligand therapy in prostate cancer. This review summarizes the current evidence and clinical relevance of these biomarkers. As [177Lu]Lu-PSMA radioligand therapy is increasingly being introduced into earlier treatment lines of prostate cancer management, the identification of reliable imaging biomarkers for response prediction and outcome assessment is becoming increasingly important. Quantitative PSMA PET/CT parameters such as whole-body (WB) mean standardized uptake value (SUVmean), WB PSMA-positive tumor volume, and tumor load, as well as qualitative features including disease distribution and phenotype (e.g., visceral metastases and FDG-avid, PSMA-negative discordant lesions), have been associated with treatment response, progression-free survival, and overall survival. However, the clinical utility of these imaging biomarkers is limited by heterogeneous study designs, small cohorts, and a lack of standardization in image acquisition, quantification, and cutoff definitions. This review critically appraises available data on baseline PSMA PET/CT-based prognostic and potentially predictive biomarkers for RLT and identifies the methodological barriers that must be addressed before these biomarkers can be implemented in clinical practice.