The VISION Forward: Recognition and Implication of PSMA−/¹⁸F-FDG+ mCRPC

Simplified schematic of spectrum of PSMA and ¹⁸F-FDG uptake in mCRPC lesions. Tumor aggressiveness generally increases from left to right, although there can be aggressive tumors without marked hypermetabolism (e.g., neuroendocrine phenotype). Prognosis is also poorer as tumor aggressiveness increases. Vertical dashed lines designate yet-to-be-defined borders of PSMA and ¹⁸F-FDG avidity of total tumor burden, which may lead to different therapy strategies. RX1 = in tumors with mainly PSMA+ disease, PSMA RLT may be primary choice of therapy; RX2 = in tumors with mixed PSMA and ¹⁸F-FDG avidity, combination therapy (PSMA RLT, chemotherapy, immunotherapy, ADT) may be considered; RX3 = in tumors with low or no PSMA expression and discordant ¹⁸F-FDG+ disease, non-RLT may be mainstay strategy, although interventions may be instituted to shift tumor phenotype to left for enabling additional therapeutic approaches that may include PSMA RLT.