PSMA-targeted PET imaging in patients with metastatic triple-negative breast cancer: results of the prospective PRISMA trial.

Abstract

Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) improves survival in metastatic castration-resistant prostate cancer. PSMA is also expressed in triple-negative breast cancer (TNBC), a subtype with limited treatment options. This prospective study assessed PSMA uptake on [⁶⁸Ga]Ga-PSMA-11 PET/CT in patients with metastatic TNBC (mTNBC) to evaluate the feasibility of PSMA-targeted RLT. This single-center prospective study enrolled patients with progressive mTNBC. Each patient underwent [¹⁸F]FDG PET/CT followed by [⁶⁸Ga]Ga-PSMA-11 PET/CT. Visual PSMA positivity was defined as uptake greater than healthy liver in most lesions. For quantitative analysis, target lesions (TLs) ≥ 1.5 cm and PERCIST-measurable on FDG PET/CT were anatomically matched to PSMA PET/CT. SUVmax was measured and compared to liver background. Twenty patients (median age 53.5 years; median 3 prior systemic therapies) were included. On visual assessment, 50.0% had PSMA uptake exceeding liver in most lesions. Quantitative analysis included 106 FDG-avid TLs; 67.0% showed PSMA SUVmax above liver. On a per-patient basis, 35.0% had all TLs and 30.0% had most TLs above liver SUVmean. However, 65.0% had at least one lesion below liver background, indicating heterogeneity. Higher PSMA uptake was associated with fewer prior treatments, prior immunotherapy, and low androgen receptor expression. PSMA PET/CT identified brain metastases in 10.0% of patients. [⁶⁸Ga]Ga-PSMA-11 PET/CT revealed clinically relevant PSMA expression in a subset of mTNBC patients. These results support further investigation of PSMA-targeted RLT in this biomarker-defined population.