Prognostic implications of dual tracer PET/CT: PSMA ligand and [18F]FDG PET/CT in patients undergoing [177Lu]PSMA radioligand therapy

Background Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with 177 Lu-labeled PSMA ligands has achieved remarkable results in advanced disease stages of metastatic castration-resistant prostate cancer (mCRPC). However, not all patients benefit from this therapy. Different treatment responses could be explained by tumor heterogeneity triggered by progression and the number of prior treatments. PSMA-negative lesions can be missed on PSMA ligand PET/CT, which subsequently results in an underestimation of tumor burden. Conversely, high FDG uptake may also be an indicator of tumor aggressiveness and thus a poor prognostic marker for response to RLT and overall survival (OS). The aim of this analysis was to investigate the prognostic value of combined PSMA ligand PET/CT and [ 18 F]fluorodeoxyglucose (FDG) PET/CT for outcome prediction in patients undergoing RLT. Materials and methods This bicentric analysis included 54 patients with mCRPC who underwent both FDG and PSMA ligand PET/CT imaging before RLT. In all patients, the pattern of PSMA ligand and FDG uptake was visually assessed. Patients with at least one FDG-positive, but PSMA-negative (FDG+/PSMA−) lesions were compared to patients without any FDG+/PSMA− lesions. A log-rank analysis was used to assess the difference in OS between subgroups. Results Median OS was 11 ± 1.8 months (95% CI 7.4–14.6). A significantly lower OS ( p