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Abstract
BackgroundProstate-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 methodsThis 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.ResultsMedian 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).ConclusionFDG+/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.
Highlights
In advanced prostate cancer, tumor progression under androgen deprivation marks the transition from a hormone-sensitive to a castration-resistant stage of disease [1]
Whereas encouraging results could be shown for patients receiving radioligand therapy (RLT) [14, 15], the subjects excluded from the trial due to FDG+/Prostate-specific membrane antigen (PSMA)− lesions had a very poor overall survival (OS) under standard of care [16]
Fifty-four patients (Würzburg: n = 26; Freiburg: n = 28) who underwent dual tracer PET/CT before at least one cycle of PSMA-targeted RLT were included in this analysis
Summary
Tumor progression under androgen deprivation marks the transition from a hormone-sensitive to a castration-resistant stage of disease [1]. Prostate-specific membrane antigen- (PSMA) targeted radioligand therapy (RLT) with [177Lu]-labeled PSMA-ligands has achieved remarkable results in advanced disease stages [7]. 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). High FDG uptake may be an indicator of tumor aggressiveness and 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. A log-rank analysis was used to assess the difference in OS between subgroups
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