Added Value of Interim FDG PET/CT in Resolving PSA-PSMA Discordance during PSMA-targeted Radioligand Therapy

PSMA-targeted radioligand therapy (RLT) is effective in metastatic castration-resistant prostate cancer, but interpretation is challenging when PSA rises despite apparent response on post-therapy 177 Lu-PSMA SPECT/CT. We present 2 patients with this PSA-PSMA discordance after 2 cycles: 177 Lu-PSMA post-therapy SPECT/CT showed a significant reduction in PSMA-derived tumor volume, yet PSA levels progressed. 18 F-FDG PET/CT performed after 2 cycles clarified disease status by revealing new hypermetabolic skeletal and visceral lesions, consistent with progression. PSMA-targeted RLT was discontinued early in both cases. 18 F-FDG PET/CT may resolve discordant PSA and PSMA findings and help prevent futile continuation of ineffective PSMA‑targeted RLT.