Responses to medical treatment in patients with metastatic unresectable small intestinal neuroendocrine tumors – A single center study of 378 patients

Abstract Small intestinal neuroendocrine tumors (siNET) are rare malignancies, often diagnosed at advanced stages with metastatic spread. While surgery is the only curative treatment, medical therapies, including somatostatin analogues (SSA), peptide receptor radionuclide therapy (PRRT), and other systemic treatments, are essential for disease stabilization. The aim was to assess median progression free survival (mPFS), and prognostic factors for the most frequently used medical treatment modalities in patients with unresectable disease. It was a retrospective single‐center cohort study, including 378 patients diagnosed with siNET between 2000 and 2020. The median overall survival (mOS) for the cohort was 97 (95% CI: 83–111) months. Median PFS for octreotide and lanreotide treatment/treated patients ( n = 255) was 30 (95% CI: 24–36) months and 5 years PFS was 32%, with no significant difference between the two agents. Risk factors for disease progression included age, Ki‐67 index, and gender (female as a protective factor). Median PFS for PRRT ( n = 140) was 31 (95% CI: 25–37) months. Thirty‐seven patients who had PFS > 18 months after the first 4 cycles received another 2 cycles of PRRT. Median PFS after the first 4 cycles was 37 (95% CI: 30–44) months versus 10 (95% CI: 6–14) months after the 2 additional PRRT cycles. Patients treated with everolimus had a median PFS of 5 (95% CI: 0.3–10) months, and chemotherapy with streptozocin and 5‐fluorouracil resulted in a median PFS of 8 (95% CI: 5–11) months. In conclusion, SSA remains the cornerstone of first‐line therapy for unresectable siNET, with PRRT offering a valuable alternative for patients with progression on SSA. Re‐introduction of PRRT with 2 additional cycles had reduced efficacy compared with the initial treatment. PFS was short in non‐somatostatin receptor‐based therapies like everolimus and chemotherapy.