De Novo Small Cell Neuroendocrine Carcinoma of the Prostate: Molecular Heterogeneity on Triple-Tracer PET/CT and Its Implications for Personalized Treatment Strategy

De novo small cell neuroendocrine carcinoma of the prostate is a rare, aggressive malignancy with heterogeneous molecular characteristics. We report the case of a patient with metastatic prostatic small cell neuroendocrine carcinoma that showed variable tracer avidity on triple-tracer PET/CT ([¹⁸F]FDG, [⁶⁸Ga]Ga-DOTATATE, and [⁶⁸Ga]Ga-PSMA-11). All lesions demonstrated intense [¹⁸F]FDG avidity, reflecting dedifferentiated biology. In contrast, [⁶⁸Ga]Ga-DOTATATE PET/CT showed uptake in only half of the lesions, predominantly in infradiaphragmatic lesions, whereas there was no uptake of [⁶⁸Ga]Ga-PSMA-11 PET/CT across all lesions. This striking discordance highlights the complementary role of triple-tracer PET/CT in characterizing tumor heterogeneity, accurate staging, and planning personalized imaging and therapeutic strategies in such aggressive malignancies.