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

Abstract

Background Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with 177Lu-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 [18F]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 < 0.001) was found in patients with at least one FDG+/PSMA− lesion at baseline PET/CTs (n = 18) with a median OS of 6.0 ± 0.5 months (95% CI: 5.0–7.0 months). In comparison, patients without any FDG+/PSMA− lesions (n = 36) had a median OS of 16.0 ± 2.5 months (95% CI: 11.2–20.8 months). Conclusion FDG+/PSMA− lesions are a negative predictor of overall survival in patients with mCRPC undergoing RLT. However, it remains to be determined if patients with FDG+/PSMA− lesions should be excluded from PSMA RLT.

PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

“…Therefore, weighting between SUV and TV, future studies may also investigate such sophisticated volumetric quantification approaches for outcome prediction [15]. A dual-radiotracer approach using PSMA-PET and 2-deoxy-2-[F-18]fluoro-D-glucose has also been performed [2,29], and intertumoral heterogeneity in PC assessed by both radiotracers may be of clinical significance for OS in a manner similar to established dual-tracer imaging protocols for neuroendocrine tumors [30,31]. Therefore, future studies may also consider findings on PSMA-PET with simultaneous increased glucose consumption, and thus, the predictive potential of FDG(+)/PSMA(-) lesions for early biochemical response could also be tested.…”

177Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer

“…Of the study group, 18 of 54 (33%) patients had FDG+/PSMAlesions at PET/CT scan. They showed that FDG positive and PSMA negative uptake was a negative predictor for overall survival (6.0 ± 0.5 months vs. 16 ± 2.4 months) [58].…”

Biomarkers in Prostate-Specific Membrane Antigen Theranostics

“…Hence, addition of FDG PET/CT to identify discordant disease appears to assist in optimal selection of patients most likely to benefit from PSMA-TRT. In another study, retrospective comparison of patients with at least one FDG-positive, but PSMA-negative (FDG+/PSMA-) lesion to patients without any FDG+/PSMA- lesions revealed a significant lower OS in the latter group, providing corroborating evidence that FDG+/PSMA- lesions are a negative predictor of OS in patients with mCRPC undergoing RLT [ 20 ].…”