Clinical Outcomes of¹⁷⁷Lu-DOTATATE Peptide Receptor Radionuclide Therapy in Patients with Skeletal Metastases from Neuroendocrine Tumors: Insights from Real-World Experience

Skeletal metastases portend a poor prognosis for patients with neuroendocrine tumors (NETs). Literature on peptide receptor radionuclide therapy (PRRT) specific to patients with skeletal metastases from NETs is scarce. This study assessed real-world clinical outcomes of ¹⁷⁷Lu-DOTATATE PRRT in this patient subgroup. <b>Methods:</b> Data from consecutive patients with well-differentiated NETs and skeletal metastases treated with ¹⁷⁷Lu-DOTATATE at our center from January 2014 until August 2024 were retrospectively reviewed. Safety, efficacy, progression-free survival (PFS), and overall survival (OS) outcomes were analyzed. <b>Results:</b> In total, 288 PRRT cycles were administered to 74 patients. The median number of PRRT cycles was 4 (interquartile range, 2-6), and the median cumulative activity was 21.3 GBq (interquartile range, 11.1-33.3 GBq). The best objective response rates, evaluated using modified M.D. Anderson criteria (bone metastases) and RECIST 1.1 (overall response), were 31% and 23%, respectively, for 62 evaluable patients. The skeletal metastases burden (≤10 vs. >10 sites) did not significantly affect objective response rates. Among the 23 patients with bone pain (31%), 39% reported complete resolution and 52% experienced a partial reduction after treatment. Grade 4 or 5 adverse events occurred in 12% of patients, with anemia, thrombocytopenia, leukopenia, and neutropenia each occurring in fewer than 5% of patients. Skeletal-related events were noted in 20% of patients. The median PFS and OS were 29 mo (95% CI, 18.0-39.9 mo) and 44 mo (95% CI, 32.8-55.2 mo), respectively. Multivariate Cox regression analysis revealed that higher cumulative activity (≥29.6 GBq) was the strongest independent predictor of improved PFS (hazard ratio [HR], 0.15; <i>P</i> < 0.001) and OS (HR, 0.11; <i>P</i> < 0.001), whereas serum alkaline phosphatase elevation (HR, 2.68; <i>P</i> = 0.048) and male sex (HR, 3.48; <i>P</i> = 0.007) were associated with worse OS rates. <b>Conclusion:</b> ¹⁷⁷Lu-DOTATATE PRRT is an effective treatment modality for patients with skeletal metastases from NETs (regardless of metastatic burden), with a favorable safety profile and favorable survival outcomes. Serum alkaline phosphatase monitoring is essential in this patient cohort. Achieving an optimal cumulative activity is crucial to maximizing the survival benefit of patients receiving PRRT.