Enzalutamide induces PSMA upregulation in castration-resistant prostate cancer even in patients having previously progressed on enzalutamide

Ziel/Aim There is preliminary evidence for prostate-specific membrane antigen (PSMA) upregulation effects of androgen receptor blockade in prostate cancer. In an attempt to find the best condition for PSMA radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC) patients, we evaluated the effect of oral enzalutamide in each individual.

Methodik/Methods 10 patients with advanced mCRPC scheduled for PSMA radioligand therapy were examined with Ga-68-PSMA-11 PET/CT before and after a mean of 2 weeks of enzalutamide 160 mg/d. Imaging results were compared using total PSMA tumor burden quantification. We assessed whole body total lesion PSMA (TLP), defined as SUV_mean*PSMA tumor volume using the open-source software Metavol and we calculated whole body total lesion PSMA to liver ratio (TLP-LR).

Ergebnisse/Results The mean, median and minimum increase of TLP-LR in the cohort was 49 %, 39 % and 10 % respectively. This increase was statistically significant (p < 0.01), while PSA values did not change significantly (p = 0.8). 7 of the 10 patients had previously undergone enzalutamide treatment with eventual progression, formally classified as treatment failure. No side effects were noted in the short-term.

Schlussfolgerungen/Conclusions Our results suggest that enzalutamide could be strongly considered as a PSMA radioligand treatment enhancing primer medication, which may increase PSMA expression by a dimension of about 50 % in mCRPC. The effect was shown even in patients having previously failed enzalutamide treatment for arrest of progression in the mCRPC setting.

 

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