Survival and Symptomatic Relief After Cytoreductive Hepatectomy for Neuroendocrine Tumor Liver Metastases: Long-Term Follow-up Evaluation of More Than 500 Patients

Abstract

Background: Distant metastases are the strongest predictor of poor prognosis for patients with neuroendocrine tumors (NETs). Cytoreductive hepatectomy (CRH) can relieve symptoms of hormonal excess and prolong survival for patients with liver metastases (NETLMs), but long-term outcomes are poorly characterized.

Methods: This retrospective single-institution analysis analyzed patients who underwent CRH for well-differentiated NETLMs from 2000 to 2020. Kaplan-Meier analysis estimated symptom-free interval and overall and progression-free survival. Multivariable Cox regression analysis evaluated factors associated with survival.

Results: The inclusion criteria were met by 546 patients. The most common primary sites were the small intestine (n = 279) and the pancreas (n = 194). Simultaneous primary tumor resection was performed for 60 % of the cases. Major hepatectomy comprised 27% of the cases, but this rate decreased during the study period (p < 0.001). Major complications occurred in 20%, and the 90-day mortality rate was 1.6%. Functional disease was present in 37 %, and symptomatic relief was achieved in 96%. The median symptom-free interval was 41 months (62 months after complete cytoreduction and 21 months with gross residual disease) (p = 0.021). The median overall survival was 122 months, and progression-free survival was 17 months. In the multivariable analysis, worse overall survival was associated with age, pancreatic primary tumor, Ki-67, number and size of lesions, and extrahepatic metastases, with Ki-67 as the strongest predictor (odds ratio [OR], 1.90 for Ki-67 [3-20%; p = 0.018] and OR, 4.25 for Ki-67 [>20%; p < 0.001]).

Conclusion: The study showed that CRH for NETLMs is associated with low perioperative morbidity and mortality and excellent overall survival, although the majority will experience recurrence/progression. For patients with functional tumors, CRH can provide durable symptomatic relief.

Fig. 1

Trends in the use of major hepatectomy and intraoperative ablation over time. Data are shown as the percentage of all hepatectomies performed per year. The rate of major hepatectomy decreased during the study period (p < 0.001), whereas the use of intraoperative ablation increased (p < 0.001)

Fig 2

Symptom-free interval from hepatectomy for patients who experienced symptomatic relief stratified by extent of cytoreduction (p = 0.021). Curves are truncated when fewer than five patients remain at risk

Fig. 3

Overall survival (OS) and progression-free survival (PFS) from hepatectomy. A Stratification of OS (p = 0.038) and PFS (p < 0.001) by primary tumor site. B Stratification of OS (p = 0.06) and PFS (p < 0.001) by extent of cytoreduction. C Stratification of OS (p < 0.001) and PFS (p < 0.001) by Ki-67 index. A loess smoother was used to generate summary survival curves for each of the Ki-67 subgroups after multiple imputation. Survival curves are truncated when fewer than five patients remain at risk (A–B) or after the last documented event (C)