Carcinoid Syndrome Impacts Long-Term Outcomes After Hepatectomy for Small Bowel Neuroendocrine Tumor Liver Metastasis

The prognostic significance of carcinoid syndrome (CS) in patients with neuroendocrine tumors (NETs) remains unclear. We aimed to evaluate its significance on surgical and long-term outcomes in a well-defined cohort of patients undergoing cytoreductive hepatectomy for small bowel NET liver metastasis (sbNETLM).

Patients undergoing cytoreductive hepatectomy between January 2000 and December 2020 were included (CS, n = 154; non-functional, n = 133); post-progression analysis extended through December 2023 in 191 patients.Query RESULTS: Age (60 vs. 63 years; p = 0.059) and sex distribution (47% vs. 54% male; p = 0.278) were similar in patients with CS compared with non-functional sbNETLM. CS was associated with more (p < 0.001) and larger (p < 0.001) hepatic metastases, requiring more frequent major hepatectomies (p < 0.001). Postoperative morbidity (22% vs. 21%; p = 0.925) and 90 day mortality (1% vs. 2%; p = 0.666) were similar in major resections. In CS patients, median overall survival (mOS) and median progression-free survival (mPFS) were shorter (mOS: 10.1 vs. 12.5 years, p = 0.035; mPFS: 1.6 vs. 2.4 years, p = 0.015). In subgroups with extensive tumor burden, CS was linked to shorter mOS (9.2 vs. 15.3 years, p = 0.028). Post-progression, 50% of CS patients and 41% of initially non-functional sbNETLM developed secondary CS, increasing the risk of carcinoid heart disease and mortality from cardiac and renal failure. CS was the strongest liver metastasis-specific predictor of mortality in multivariable regression analysis (HR 1.73, p = 0.004).

While surgical risk is not elevated, long-term survival is reduced in CS. Secondary CS can develop after tumor progression, even in initially non-functional sbNETLM, further worsening prognosis. Regular screening and proactive management of CS may improve long-term outcomes.