Evaluation of PSMA expression changes on PET/CT before and after initiation of novel antiandrogen drugs (enzalutamide or abiraterone) in metastatic castration-resistant prostate cancer patients

To investigate the association between Prostate-Specific Membrane Antigen (PSMA) expression changes on positron emission tomography–computed tomography (PET/CT) and the response to treatment following the start of enzalutamide or abiraterone in metastatic castration-resistant prostate cancer (mCRPC) patients. All consecutive 68Ga-PSMA-11 PET/CT scans routinely performed at our institution during more than 4 years were retrospectively screened for inclusion. We included mCRPC patients with a baseline PSMA PET/CT performed less than 2 months before the start of either enzalutamide or abiraterone, and a follow-up PSMA PET/CT performed no more than a year after, while still under those novel antiandrogen drugs (NAD). The associated clinical records were reviewed. Patients were considered treatment responders if they presented decreasing PSA levels > 50% or a radiological response based on RECIST 1.1 criteria. PSMA expression changes on the follow-up PET/CT were assessed using per-patient dominant response criteria to classify patients as PSMA-responders (complete disappearance of pathologic PSMA uptake, or a decreased uptake of the majority of lesions) or PSMA-non-responders (new PSMA-expressing lesions, increased uptake of the majority of lesions, or stable PSMA expression of the disease). Descriptive statistics and measures of associations (two-sided Fisher’s exact test and Phi coefficient) were calculated. A total of 11 and 15 patients were included in the enzalutamide and abiraterone groups. Median follow-up was 110 (IQR 76–124) and 87 (IQR 71–242) days, respectively. All treatment responders (3 enzalutamide and 4 abiraterone) were considered PSMA-responders, and all treatment non-responders (8 enzalutamide, 11 abiraterone) were considered PSMA-non-responders. PSMA PET response was thus perfectly associated with conventional response criteria (p = 0.006, Phi = 1 for enzalutamide; p = 0.001, Phi = 1 for abiraterone). In our cohort, no PSMA expression flare phenomenon was detected on follow-up PET/CT scans at a median follow-up of 3 months. However, an early and short-lived flare cannot be excluded. This retrospective study suggests that, after a median follow-up of 3 months under enzalutamide or abiraterone, PSMA expression changes on PET/CT are strongly associated with response to treatment. Prospective studies are needed to better understand PSMA expression dynamics following the start of enzalutamide and abiraterone, along with the role of PSMA PET/CT in response assessment.