Androgen deprivation therapy and its modulation of PSMA expression in prostate cancer: mini review and case series of patients studied with sequential [ 68 Ga]-Ga-PSMA-11 PET/CT

[68Ga]-Ga-PSMA-PET/CT (PSMA-PET) is routinely performed in many patients who have received or are receiving Androgen Deprivation Therapy (ADT). However, potentially occurring interactions of ADT on PSMA expression in men with Prostate cancer (PCa) have not been yet fully investigated nor understood. Since an influence of ADT on the expression of PSMA was observed in both in vitro and in vivo studies, relevant implications for image interpretation and PSMA-radioligand therapy (RLT) timing may arise from a better understanding of such a phenomenon. In this mini review, we analyzed the most relevant clinical literature on this topic (PubMed). We also presented a case series of two patients who underwent sequential PSMA-PET during ADT. We found a total of five studies which investigated the effect of ADT on PSMA expression on 43 patients at different stages of the natural history of the disease. Four studies investigated the effect of short-term ADT and detected an increase of PSMA expression (more or less heterogeneous). The remaining study investigated the long-term ADT effect, demonstrating a decrease in most lesions. In our case series, despite a complete PSA response, we observed a rapid up-regulation of PSMA expression in our PSMA-PET imaging immediately after ADT administration. Although clinical evidence remains inconclusive, a short-term ADT administration may seem to increase PSMA expression in some selected cases, while long-term ADT might have the opposite effect at least in castrate sensitive prostate cancer (CSPC) patients, even if potentially leading to an early selection of those lesions most at risk of becoming castrate resistant.