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 patients, predominantly having previously progressed on enzalutamide treatment.
Ten patients with advanced mCRPC scheduled for PSMA radioligand therapy were examined with 68Ga-PSMA-11 PET/CT before and after a mean of 11.8 days of enzalutamide 160 mg/day. Imaging results were compared using total PSMA tumor burden quantification. We assessed whole-body total lesion PSMA (TLP), defined as SUVmean × tumor volume and calculated TLP-to-liver ratio (TLP-LR), TLP-to-parotid gland ratio (TLP-PR), and TLP-to-kidney ratio (TLP-KR).
The mean (median) increase of TLP-LR, TLP-PR, and TLP-KR in the cohort was 49.3% (38.8%), 45.1% (23.5%), and 54.9% (37.6%), respectively. These increases were statistically significant (p = 0.002, p = 0.014, and p = 0.014), while PSA values did not change significantly (p = 0.846). Seven 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.
Our results suggest that enzalutamide could be considered as a PSMA radioligand treatment enhancing primer medication, which may increase PSMA expression by a dimension of 50% in mCRPC. The effect was shown even in patients having previously failed enzalutamide treatment for arrest of progression in the mCRPC setting. Our observation deserves evaluation in a prospective setting.
European journal of nuclear medicine and molecular imaging. 2020 Jan 03 [Epub ahead of print]
Florian Rosar, Sebastian Dewes, Martin Ries, Andrea Schaefer, Fadi Khreish, Stephan Maus, Hendrik Bohnenberger, Johannes Linxweiler, Mark Bartholomä, Carsten Ohlmann, Samer Ezziddin
Department of Nuclear Medicine, Saarland University, Kirrberger Str. 100, Geb. 50, 66421, Homburg, Germany., Department of Urology, Saarland University, Homburg, Germany., Department of Nuclear Medicine, Saarland University, Kirrberger Str. 100, Geb. 50, 66421, Homburg, Germany. .