Dual-Tracer ⁶⁸Ga-PSMA and ⁶⁸Ga-DOTATATE PET/CT in Advanced Prostate Cancer: Persistent PSMA Expression Despite Clinically Suspected Treatment-Emergent Neuroendocrine Differentiation.

Abstract

BackgroundNeuroendocrine differentiation in advanced prostate cancer is associated with aggressive behavior, resistance to androgen receptor pathway inhibition, and altered tracer expression. Although reduced prostate-specific membrane antigen (PSMA) expression and increased somatostatin receptor expression are often assumed in treatment-emergent neuroendocrine prostate cancer (t-NEPC), direct intrapatient comparisons using dual-tracer imaging remain limited.Materials and methodsWe retrospectively analyzed eight patients with advanced prostate cancer who underwent both ⁶⁸Ga-PSMA PET/CT and ⁶⁸Ga-DOTATATE PET/CT on consecutive days because of clinically suspected treatment-emergent neuroendocrine differentiation. Histopathological evidence was available in one patient; the remaining seven were included based on clinical suspicion. Patient characteristics were extracted from a clinical dataset, and imaging findings were abstracted from original nuclear medicine reports. Lesions were categorized as concordant, PSMA-dominant, PSMA-positive/DOTATATE-negative, or DOTATATE-positive/PSMA-negative.ResultsAll eight patients had metastatic castration-resistant prostate cancer (mCRPC) at dual-tracer imaging. Based on original clinical reports, PSMA uptake was equal to or greater than DOTATATE uptake in all eight patients. No DOTATATE-positive/PSMA-negative sites were documented, whereas PSMA-positive/DOTATATE-negative sites were described in several patients, particularly in lung and liver metastases and selected nodal and skeletal lesions.ConclusionsIn advanced prostate cancer with clinically suspected treatment-emergent neuroendocrine differentiation, PSMA uptake frequently persisted and generally predominated over DOTATATE uptake. No DOTATATE-positive/PSMA-negative sites were documented, whereas PSMA-positive/DOTATATE-negative sites were observed in several patients, consistent with substantial spatial and intrapatient heterogeneity. These findings support assessment of the actual PSMA imaging phenotype before excluding PSMA-targeted approaches solely on the basis of suspected neuroendocrine differentiation.