Relapse factors for ileal neuroendocrine tumours after curative surgery: A retrospective French multicentre study

Abstract

Aim

To evaluate the characteristics of postoperative relapse, predictive factors and time to relapse after curative surgery for well-differentiated neuroendocrine tumours of the ileum, without hepatic or other distant metastases.

Methods

Clinical data of patients entered into the Groupe d’étude des Tumeurs Endocrines database were collected and analysed retrospectively to identify factors predictive of relapse.

Results

Among 100 patients followed for a median of 56.5 (range 1–290) months, 42 relapsed after a median follow-up of 57.5 (range 6–176) months, with liver lesions in 27 (64.3%). Median disease-free survival (Kaplan–Meier) was 88 months (95% confidence interval 72–115). Disease-free survival was shorter for emergency surgery patients (p < 0.01), patients with distant mesenteric lymph-node metastases (p < 0.01), with fortuitous diagnosis (p = 0.02), with tumour diameter >20 mm (p = 0.02), and those with multiple tumours (p = 0.07). Multivariate analysis retained emergency surgery (odds-ratio 4.04 [95% confidence interval 2.01–8.11]), distant mesenteric lymph-node metastases (odds-ratio 2.53 [95% confidence interval 1.22–5.25]), and multiple tumours (odds-ratio 2.14 [95% confidence interval 1.01–4.50]), as being significantly associated with relapse.

Conclusion

Patients who underwent emergency surgery, with distant mesenteric lymph-node metastases or with multiple ileal tumours relapsed earlier. Closer monitoring for the patients with these risk factors may be required.

Introduction

Digestive neuroendocrine tumours are uncommon but their prevalence is increasing [1], [2], [3]. Analysis of 35,825 neuroendocrine tumours entered into the Surveillance, Epidemiology, and End Results (SEER) database showed that the most frequent sites were the rectum and small intestine [2], notably 49.6% in the ileum [3]. Neuroendocrine tumours of the small intestine are most often well-differentiated, with a high risk of metastases [2], [3] that depends on the tumour size [4]. These tumours are often diagnosed late at an advanced stage because they remain asymptomatic for a long time. The carcinoid syndrome is observed in 2–5% of these patients and only in the presence of hepatic metastases or a large tumour volume [5], [6], [7], [8]. Most often, the disease is revealed by an occlusive syndrome resulting from retractile mesenteric fibrosis, endoluminal obstruction or carcinosis, but also non-specific abdominal pain [1], [8], [9], [10], [11].

Curative treatment is exclusively surgical [12]. However, survival studies showed that, even after curative surgical resection, delayed relapse could occur. In light of the rarity and the heterogeneity of reported series, prognostic factors have been poorly evaluated and differ from one study to another. The most frequently cited are tumour size and hepatic metastases or carcinoid cardiopathy [3], [4], [13], [14], [15], [16], [17], [18], [19], [20], [21]. The prognosis relevance of the European Neuroendocrine Tumor Society (ENETS) staging and grading was recently shown in patients with neuroendocrine tumours of midgut and hindgut origins [22].

After curative resection of the primary tumour, monitoring is necessary but relapse characteristics have not been adequately examined and the surveillance criteria remain poorly defined. To our knowledge, no study has assessed the risk of relapse in the subgroup of patients who had undergone complete resection of the primary tumour and lymph nodes.

The main objective of this retrospective study was to evaluate the characteristics of relapse and the factors predictive of it based on a large multicenter population of patients with well-differentiated ileal neuroendocrine tumours, without hepatic or other distant visceral metastases, that had undergone curative surgery.