Surgical debulking versus non-surgical management for the control of carcinoid syndrome in metastatic small bowel neuroendocrine tumors.

4147 Background: Somatostatin analogues (SSAs) are first-line systemic therapeutics for tumor- and symptoms control in well-differentiated small bowel neuroendocrine tumors (SBNETs) with liver metastases. Surgical debulking of neuroendocrine tumor liver metastases (NETLMs) has historically been associated with symptom control in patients with carcinoid symptoms. Herein, we compare clinical outcomes in patients with metastatic SBNETs treated with surgical debulking for NETLMs to SSA alone or in combination with non-surgical liver directed therapies (LDTs) i.e. bland embolization or radioembolization. Methods: Patients with serotonin-producing SBNETs and NETLMs with documented symptoms of carcinoid syndrome were included in this retrospective chart review. Primary outcome was symptom-free-interval (SFI), defined as the time from start of treatment until return/worsening of symptoms. Patients were censored for SFI if a new line of tumor-directed therapy was initiated for radiographic disease progression in the absence of return/worsening of symptoms. Time to event outcomes were analyzed using Kaplan-Meier estimations, log-rank test, and Cox proportional hazards regression model. Medians were compared using the Mann–Whitney U test. Results: Between 2018 – 2024, 64 consecutive patients with carcinoid symptoms were included for analysis. 42 patients (65.6%) underwent surgical debulking (SDB) of NETLMs and 22 patients were treated with SSA alone (n = 14) or SSA plus LDT (n = 8). The proportion of patients reporting symptom improvement was not significantly different between the SDB and non-surgical (NS; SSA + LDT) groups (SDB = 38, 90.5% vs. NS = 19, 86.4%; p = 0.68). Among those with symptom improvement (n = 57), SFI was significantly longer in the SDB group (median SFI; SDB = 28.2 months [m] vs. NS = 15.9 m; p = 0.004). Radiographic PFS was also significantly prolonged in the SDB group (SDB = 26.1 m vs. NS = 12 m; HR, 0.53; 95% CI, 0.29 – 0.95; p = 0.03). Within the SDB group, there was no significant difference in SFI between patients who continued to receive SSA post-op (n = 23) and those in whom SSA was discontinued (n = 19) post-op (28 m vs. 30.6 m; p = 0.85). Post-treatment median nadir serotonin was significantly lower in the SDB group (total N = 41 [SDB = 31 + NS = 10]; SDB = 299 ng/mL vs. NS = 947.5 ng/mL; p < 0.001). Median percentage decrease (from pre-treatment to nadir values) in serum serotonin was higher in the SDB group with the difference approaching significance (total N = 30 [SDB = 22 + NS = 8]; SDB = 80.9% vs. NS = 51.5%; p = 0.06). Conclusions: Despite the frequent use of SSAs, surgical debulking of NETLMs in patients with carcinoid symptoms remains superior for symptom control and should therefore be considered in these patients.