Response Evaluation Criteria in Grade 1/2 Neuroendocrine Tumors (RECIN)

Abstract

Accurate response assessment in well-differentiated grade 1/2 neuroendocrine tumors (NETs) remains a major clinical challenge. Conventional size-based radiographic criteria such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 often fail to capture the slow, indolent nature of NETs. In these tumors, meaningful survival benefits, particularly after peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTATATE, occur without significant tumor shrinkage, while treatment-related necrotic or inflammatory changes can mimic progression. Several modified anatomical criteria, including Choi and mRECIST, have attempted to address these limitations, but results have been inconsistent and largely retrospective. Somatostatin receptor (SSTR)-PET/CT with [⁶⁸Ga]Ga-labeled analogues offers the opportunity to quantify biological response at the molecular level, reflecting alterations in receptor density and viable tumor burden. The Response Evaluation Criteria in Neuroendocrine Tumors (RECIN), developed from a post-hoc analysis of the phase II LuCAP trial, integrates semi-quantitative SSTR-PET parameters with conventional CT metrics. Using the summed SULpeak of up to five of the hottest lesions (up to two per organ), RECIN defines molecular partial response as a ≥25% reduction in summed SULpeak, while maintaining RECIST safeguards for progression. Applied to the prospective LuCAP trial dataset, RECIN identified additional responders, detected response earlier, and predicted progression-free survival more accurately than RECIST. By harmonizing biological and morphological information, RECIN provides a practical and reproducible framework tailored to the indolent, receptor-driven biology of NETs. Prospective multicenter validation, and correlation with longer term outcomes are needed to establish RECIN as standardized response criteria for PRRT as well as other treatment modalities for well-differentiated NETs.