Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted
radioligand therapy (RLT) in metastatic castration-resistant prostate cancer (mCRPC), some patients
show worsening disease during PSMA-RLT. We investigated the value of combined [18F]FDG and
[
68Ga]Ga-PSMA-11 PET imaging in this setting. In n = 29 mCRPC patients with worsening disease
after a median of four cycles of [177Lu]Lu-PSMA-617 RLT, combined [18F]FDG and [68Ga]Ga-PSMA11 PET imaging was performed to detect [18F]FDG-avid lesions with low or no PSMA expression
(mismatch lesions). To evaluate prognostic implication of mismatch, survival analyses regarding
presence, location, and [18F]FDG PET-derived parameters such as SUVmax, metabolic tumor volume
(MTVm), and total lesion glycolysis (TLGm) of mismatch findings were performed. Seventeen patients
(59%) showed at least one mismatch metastasis. From the time point of combined PET imaging,
the median overall survival (OS) of patients with mismatch findings was significantly (p = 0.008)
shorter than those without (3.3 vs. 6.1 mo). Patients with a high MTVm revealed a significantly
(p = 0.034) shorter OS of 2.6 mo than patients with low MTVm (5.3 mo). Furthermore, patients
with hepatic mismatch showed a significantly (p = 0.049) shorter OS than those without (2.9 vs. 5.3
mo). Difference in OS regarding SUVmax and TLGm was not significant. In mCRPC patients with
worsening disease during PSMA-RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging
is essential to identify mismatch findings, as these are associated with poor outcomes requiring a
change in therapy management
