*4.1. Impact of Tumor Grade*

Another key finding of this study was the strong influence of tumor grade on [18F]FDG uptake and [18F]FDG kinetics of LNM, which fundamentally affects their visibility in PET. As grading is usually assessed by biopsy as part of the initial gynecological examination, this is available when PET/MRI scan is performed.

The integration of histological characteristics into a multiparametric imaging-based analysis adds complementary information. In particular, primary tumor histology changed both the weighting of the individual parameters and their cut-off values in our study.

The present data indicate that the low sensitivity of [18F]FDG PET/MRI for G2 LNM might rather be due to smaller size, low SUV, and discreet [18F]FDG kinetics compared with their hitherto often assumed lower prevalence. In fact, LNM prevalence in G2 was not significantly different from that in G3 tumors using ultrastaging as the gold standard [26]. This finding is of high clinical relevance, as a solely visual assessment of [18F]FDG PET comes with insufficient sensitivity for N-staging in G2 tumors. Under consideration of early data, it can be hypothesized that the SLN technique may achieve more accurate N-staging than visual evaluation of [18F]FDG PET/MRI in early-stage G2 carcinoma [16,27]. This is even more important as, currently, in stage T1B1 and lower (i.e., early cervical cancer below 2 cm), LN dissection of only the SLN is currently considered state of the art [2]. Thus, preoperative knowledge of positive LN has a direct impact on the surgical procedure.
