[¹⁸F]FDG PET during immunotherapy: mind the gap between evidence, imaging guidelines, and oncology practice

No specific statements regarding the use of 2-[¹⁸F]fluoro-2-deoxy-D-glucose positron-emission tomography/computed tomography ([¹⁸F]FDG PET) in the context of immunotherapy are made in current international oncological guidelines for the management of the two cancer types for which the largest body of evidence has been generated, such as melanoma and non-small cell lung cancer (NSCLC). However, practice guidelines released jointly by leading nuclear medicine societies recommended the use of [¹⁸F]FDG PET alongside computed tomography (CT) before immunotherapy initiation, for early response assessment, and in patients considered for therapy discontinuation. In the present paper we critically reviewed the available literature on the comparison between [¹⁸F]FDG PET and CT for response assessment in patients undergoing immunotherapy, with the aim to identify where metabolic imaging holds the most significant promise. In early response assessment, where an accurate discrimination between pseudoprogression and true tumor progression is necessary, [¹⁸F]FDG PET is of limited value. In contrast, there are at least two clinical scenarios in which [¹⁸F]FDG PET could outperform CT because of its high negative predictive value, that are the evaluation of response to neoadjuvant immunotherapy or before therapy discontinuation. We emphasized that the generation of robust evidence is necessary before clinical implementation, as it ensures the optimal allocation of resources and better patient care.