PSMA expression assessed by [18F]PSMA-1007 PET/CT imaging in metastatic hormone-sensitive prostate cancer patients treated with apalutamide

PSMA PET/CT (Prostate-specific membrane antigen positron emission tomography / computed tomography) has revolutionized prostate cancer imaging. While PSMA expression is influenced by androgen receptor pathway inhibitors (ARPI), few studies have examined the specific effects of apalutamide, a widely used ARPI for hormone-sensitive metastatic prostate cancer. This study evaluated the impact of apalutamide on PSMA radioligand uptake. We evaluated 17 patients with metastatic hormone-sensitive prostate cancer (mHSPC) who underwent [18F]PSMA-1007 PET/CT imaging prior to (PET1) (time from PET1 to initiation of apalutamide: 0.40 months; range 0.03–5.90 months) and during apalutamide treatment (PET2) (time from apalutamide initiation to PET2: 5.30 months; range 1.70–20.30 months). Biodistribution and tumor uptake were calculated using whole body total tumor volume (TTV), TTV-SUVmax and TTV-SUVmean and changes between imaging time points were analysed. All patients demonstrated significant clinical and biochemical PSA responses after treatment initiation (median PSA (ng/mL) 46.40 vs. 0.03, p = 0.001). On PSMA PET/CT during apalutamide therapy, patients showed an overall decrease in TTV-SUVmax, TTV-SUVmean and TTV. Median decreases in TTV-SUVmax and TTV-SUVmean were − 54% and − 28%, respectively (p = 0.006, p = 0.020). TTV exhibited a significant median decrease by -53% (p = 0.006). In 4/17 (23.5%) patients imaging and biochemical response revealed discordant results. This pilot study indicates that, in mHSPC patients, PSMA upregulation is unlikely with intermediate to long-term apalutamide therapy. However, an increase of imaging parameters with synchronous decrease of PSA levels should raise suspicion of early imaging progression, resulting in close monitoring. Further research is warranted to explore early treatment response in the hormone-sensitive stadium.