Using, ⁶⁸Ga-PSMA-11 PET/CT for therapy response assessment in patients with metastatic castration-resistant prostate cancer: an application of EAU/EANM recommendations in clinical practice.

Abstract

For patients with metastatic castration-resistant prostate cancer (mCRPC), no reliable biomarkers are currently available that predict therapeutic response or assist in treatment selection and sequencing. Using the recent European Association of Urology and European Association of Nuclear Medicine (EAU/EANM) recommendations, we aimed to (1) compare response assessment between prostate-specific membrane antigen (PSMA) positron emission tomography combined with computed tomography (PET/CT) and conventional imaging (CI) in mCRPC patients starting a first-line treatment with novel hormonal agents (NHA), and (2) perform a sequential comparative analysis of PSMA PET/CT-derived parameters after 4 and 12 weeks of therapy. Methods: Eighteen mCRPC patients who started NHA and underwent ⁶⁸Ga-PSMA-11 PET/CT before therapy initiation (baseline), at week 4 (W4) and week 12 (W12), in addition to CI (bone scintigraphy, CT) at baseline and W12, were retrospectively included. PET/CT images were quantitatively analyzed for maximum and mean standardized uptake value and total PSMA-ligand positive total lesion (PSMA-TL). Comparative analysis of PET/CT-derived parameters was performed, and patients were classified with non-progressive disease (non-PD) or progressive disease (PD) according to ⁶⁸Ga-PSMA-11 PET/CT, PSA and CI criteria. Results: Treatment response was evaluable by ⁶⁸Ga-PSMA-11 PET/CT in 16/18 (89%) patients compared to 11/18 (61%) by CI. At W12, patients with PD by ⁶⁸Ga-PSMA-11 PET/CT already met progression criteria at W4 (n = 5/16) and substantial agreement was observed between the W4 and W12 (κ = 0.74) ⁶⁸Ga-PSMA-11 PET/CT. Nonetheless, 2/16 (13%) patients were wrongly classified with PD due to a flare phenomenon on PSMA PET/CT, which disappeared at W12. Conclusion: Volumetric assessments of ⁶⁸Ga-PSMA-11 PET/CT imaging can improve response evaluation in NHA-treated patients with mCRPC. Although early response assessments at W4 need to be approached with caution due to flare, ⁶⁸Ga-PSMA-11 PET/CT imaging at 4 and 12 weeks revealed a substantial agreement in the therapy response assessment, which warrants further investigation to distinguish PD from flare at W4 and help improve our understanding of resistance to therapy.