Patterns of Progression After Peptide Receptor Radiopharmaceutical Therapy

[¹⁷⁷Lu]Lu-DOTATATE has been approved for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). It is often thought that NET progression may result in somatostatin receptor (SSTR)-negative disease because of the elimination of SSTR-positive clones. This study aimed to assess the patterns of progression and SSTR uptake in patients with NETs after peptide receptor radionuclide therapy (PRRT). Methods: In this retrospective study, we evaluated patients with NETs who received PRRT between 2016 and 2024. Imaging findings and medical oncology notes were reviewed to identify and characterize disease progression. Using postprogression SSTR PET scans, the SUV_max of the progressed lesion was measured, and qualitative radiotracer uptake was compared with baseline. Results: In total, 195 patients were treated with PRRT, and progression occurred in 107 patients (54.9%). The liver was the dominant site of progression (65 patients, 60.7%), followed by bone (27 patients, 25.3%). The mean ± SD SUV_max of the hottest lesion on SSTR PET was 54.3 ± 41.0 at baseline and 46.0 ± 35.5 after disease progression (P = 0.02). Qualitatively, postprogression SSTR PET showed equal uptake in 59.7% of patients, higher uptake in 18.2%, and reduced uptake in 19.5% compared with baseline. SSTR-negative disease was observed in 4 patients (3.7%). SSTR PET identified progression that was not seen on conventional imaging in 50 patients (46.7%). Conclusion: Most patients who experienced progression after PRRT continued to express SSTR, with a decrease in SUV_max SSTR-negative disease was rare, indicating that the majority remained eligible for retreatment with SSTR-targeted radioligands. SSTR PET identified disease progression in 46.7% of patients, emphasizing its essential role in detecting disease progression, particularly in nonmeasurable disease, such as that in bone.