High AST and the presence of liver metastases may guide for the need for FDG PET in advanced prostate cancer patients

• Liver metastases and elevated liver enzymes predict FDG+/PSMA− discordance, identifying patients who may benefit from dual-tracer PET imaging. • Dual-tracer PET reveals metabolic heterogeneity, uncovering lesions underestimated by PSMA PET alone. • Integration of serum biomarkers and imaging features supports personalized, cost-effective staging and management in mCRPC. [68Ga]/[18F] labeled Prostate Specific Membrane Antigen (PSMA) is the radiotracer of choice for imaging localized and metastatic prostate cancer with high sensitivity and specificity. On the other hand, 2-[ 18 F]fluoro-D-glucose (FDG) Positron Emission Tomograpy/Computed Tomography (PET/CT) may help to evaluate the tumor heterogeneity in patients with metastatic castration-resistant prostate cancer (mCRPC) and determine treatment eligibility for Prostate Specific Membrane Antigen (PSMA) targeted radioligand therapy (PSMA-RLT) . The aim of the study is to evaluate the biochemical and clinical parameters which can predict the presence of FDG-PSMA discordant disease. A total of 70 advanced mCRPC patients who underwent [ 68 Ga]Ga-PSMA-11 PET and FDG PET/CT between August 2016 and June 2021 were retrospectively analyzed. Inter-tumoral heterogeneity was both visually and semi-quantitatively evaluated. Baseline clinical, laboratory and PSMA PET/CT related semi-quantitative parameters were analyzed to predict FDG discordant disease with logistic regression analysis. 29/70 (41.4%) of the patients had FDG-PSMA discordant disease. Overall 427 mismatch lesions (FDG+PSMA-) were detected: the majority of these lesions were in the bones ( n = 236, 55.2%), lymph nodes ( n = 95, 22.2%), and visceral organs ( n = 88, 20.6%). Most significant parameters to predict FDG-PSMA discordant disease were liver metastases (HR= 26.5, 95%CI 2.3-302.9, P = 0.008) and serum AST (HR= 1.15, 95%CI 1.04-1.26, P = 0.007). The presence of liver metastases and elevated AST may be easily used in clinical practice to predict FDG-PSMA discordant disease.