Comparing Response Evaluation Methods for PRRT in Neuroendocrine Tumors: Insights from an Exploratory Study

Background/Objectives: Assessing treatment response in neuroendocrine tumors (NETs) remains challenging. The multifactorial mechanism of action of peptide receptor radionuclide therapy (PRRT) further complicates response evaluation, particularly in the absence of standardized criteria. This study aimed to compare different imaging-based response assessment methods after PRRT and to explore their relationship with clinical outcomes, particularly progression-free survival (PFS). Methods: In this single-center retrospective study, we analyzed NET patients treated with PRRT between 2020 and 2024 who underwent [⁶⁸Ga]Ga-DOTATOC PET/CT before and after therapy, with a minimum follow-up of 12 months. Five response criteria were evaluated: (a) Krenning Score changes; (b) adapted PERCIST criteria (MORE); (c) ZP-normalized parameter; (d) qualitative visual PET assessment; and (e) RECIST-based morphological response on contrast-enhanced CT. Imaging findings were correlated with clinical outcomes. Nonparametric analyses were performed using the MedCalc^® software. Results: Thirty-one patients (median age 63 years; 17 males) with NET were evaluated after PRRT. Post-PRRT PET/CT was performed at a median of 3 months. Response rates varied across methods, with higher rates noted using functional imaging (MORE 66%, Visual PET 68%, ZP 70%) compared to RECIST (40%) and Krenning score (21%). After a median follow-up of 37 months, 58% of patients experienced disease progression. Although no significant association was found between the response criteria and progression (p > 0.05), functional imaging showed a trend toward better correlation with longer progression-free survival. Conclusions: Functional PET-based responsecriteria suggest association with progression-free survival compared to RECIST criteria and Krenning score changes. However, given the exploratory nature of the study and its methodological limitations, these observations should be considered hypothesis-generating only. They do not provide definitive evidence of superiority over established assessment methods and therefore should not be interpreted as practice-changing.