Prostate-Specific Membrane Antigen Expression on PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer: A Retrospective Observational Study

Rationale: Monitoring therapy response in patients with metastatic castration-resistant prostate cancer ([m]CRPC) treated with novel hormonal therapies, taxanes and newly approved therapies is crucial for optimizing treatment. [⁶⁸Ga]Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computed tomography (PSMA PET/CT) is a promising target for managing treatment in patients with prostate cancer. PSMA is overexpressed in patients with mCRPC; understanding how expression might change in patients undergoing treatment could determine its potential for guiding clinical decisions. We examined PSMA expression in patients with CRPC and compared PET/CT response with prostate-specific antigen (PSA) variation as prognostic factor for progression-free and overall survival (PFS and OS). Methods: Single-centre, retrospective observational cohort study in patients with CRPC enrolled in the PSMA-PROSTATA registry study (EudraCT: 2015-004589-27). First and second (if applicable) PSMA PET/CT were performed to determine PSMA expression (absence/presence). PET/CT response was assessed as responders (patients with stable disease, partial or complete response) versus non-responders (patients with progressive disease) comparing the first with the second PET/CT PET/CT. PSA variation (increase/decrease from baseline) was assessed across the same time period. PFS was defined as time between second PET/CT and PSA recurrence or evidence of radiological progression. Results: Overall, 160 patients with CRPC were included in the analysis. At first PET/CT, nearly all (n = 152; 95.0%) patients had PSMA expression (classified as mCRPC), irrespective of prior systemic therapy. Maximized standardized uptake value (SUV_max) was positively associated with baseline PSA levels and velocity (both P<0.001). According to PET/CT response, median SUV_max on first PET/CT was numerically lower in non-responders versus responders (17.5 vs 20.4; P = 0.127). Similarly, patients with a PSA increase had significantly lower median SUV_max on first PET/CT (15.8) compared with those with a PSA decrease (30.4; P = 0.018). PSA change was, on average, 146% in non-responders and –57% in responders between first and second PET/CT (P<0.001). Agreement between PET/CT and PSA response was 79% (k=0.553, P<0.001). Among the 63 patients included in PFS/OS analyses, 76.2% had a relapse and 36.5% died before 24-month follow-up; median PFS and OS were 6.1 months and 24 months, respectively. PET/CT response, independent of PSA variation, was a significant prognostic factor for PFS. OS was not significantly different between PET/CT responders and non-responders. Conclusion: PSMA PET/CT may be a useful imaging method predictive of treatment response in patients with mCRPC, regardless of ongoing systemic therapy. Data also suggest that response assessed by PET/CT is a potentially more significant prognostic factor than PSA for PFS. Further studies are needed to understand the potential involvement of PSMA expression on survival.