Characterizing Early Disease Progression in GEP-NET Patients After Peptide Receptor Radionuclide Therapy (PRRT)

Introduction: Peptide Receptor Radionuclide Therapy (PRRT) is an established treatment for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Currently, the standard Lutathera® ([¹⁷⁷Lu]Lu-DOTA-TATE) protocol, as regulated by the FDA and Korean FDA, comprises four treatment cycles. However, a subset of patients demonstrates early disease progression following the completion of the treatment. This study aims to characterize the early progression after PRRT, defined as progression within one year after end of treatment, and to identify potential relevant factors.

Methods: We conducted a retrospective analysis of GEP-NET patients who completed the standard four-cycle PRRT protocol, who showed response of at least stable disease according to RECIST v1.1 criteria, and who had been followed up for at least one year. The study examined variables including age, sex, baseline chromogranin A (CGA) and neuron specific enolase (NSE) levels, disease duration, baseline blood counts, baseline SUVmax, Ki67 index, and tumor characteristics. The Mann-Whitney U test was used for continuous variables, and the chi-square test was employed for categorical variables, to assess differences between the groups.

Results: Among patients who received PRRT at our center since 2020, 23 met the study criteria and were analyzed. Among them, 6 patients (26.1%) exhibited progression within one year after the final day of Lutathera® therapy (the day when 4th cycle was done). Among the investigated categories, higher Ki-67 level (22% vs 7% on average, p=0.007) and higher basal Platelet-to-Lymphocyte Ratio (PLR, 208.8 vs 133.7 on average, p=0.020) were related to earlier PD. There were no significant difference of age, sex, the number of previous systemic therapy before PRRT treatment, baseline SUVmax, and baseline CGA and NSE levels between two patient groups.

Conclusions: This study's observation of early progression in a significant subset of GEP-NET patients after PRRT underscores the need for enhanced monitoring and individualized treatment strategies beyond 4 cycles. The association of higher Ki-67 levels and PLR with early progression highlights the potential of these markers in predicting treatment outcomes. Future studies should aim to validate these biomarkers in larger patient cohorts.