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.

Keywords: FDG; PET/CT; PSMA; Prostate cancer; Radioligand therapy.

Fig. 1

Corresponding axial slices of [¹⁸F]PSMA-1007 PET (first column), FDG PET (second column), and CT (third column). a 72-year-old patient with FDG+/PSMA- right hilar lymph node metastasis (black arrow; histologically proven metastasis from prostate cancer). b 65-year old patient with concordant FDG+/PSMA+ bone metastases. Fixed inverse gray-scale are displayed with SUV window setting from 0 to 10 ([¹⁸F]PSMA-1007 PET) and 0 to 5 (FDG PET), respectively

Fig. 2

Kaplan-Meier curves of median overall survival (OS) of patients with FDG+/PSMA- lesions. These patients (n = 18, red line) had an OS of 6.0 ± 0.5 months (95% CI 5.0–7.0 months), whereas the other patients (n = 36, blue line) showed an OS of 16.0 ± 2.4 months (95% CI 11.2–20.8 months; p < 0.001)