Long-term Follow-up of MEN1 Patients Who Do Not Have Initial Surgery for Small ≤2 cm Nonfunctioning Pancreatic Neuroendocrine Tumors, an AFCE and GTE Study: Association Francophone de Chirurgie Endocrinienne & Groupe d'Etude des Tumeurs Endocrines

Abstract

Objective: To report long-term follow-up of patients with multiple endocrine neoplasia type 1 (MEN1) and nonfunctioning pancreatic neuroendocrine tumors (NF-PET).

Background: Pancreaticoduodenal tumors occur in almost all patients with MEN1 and are a major cause of death. The natural history and clinical outcome are poorly defined, and management is still controversial for small NF-PET.

Methods: Clinical outcome and tumor progression were analyzed in 46 patients with MEN1 with 2 cm or smaller NF-PET who did not have surgery at the time of initial diagnosis. Survival data were analyzed using the Kaplan-Meier method.

Results: Forty-six patients with MEN1 were followed prospectively for 10.7 ± 4.2 (mean ± standard deviation) years. One patient was lost to follow-up and 1 died from a cause unrelated to MEN1. Twenty-eight patients had stable disease and 16 showed significant progression of pancreaticoduodenal involvement, indicated by increase in size or number of tumors, development of a hypersecretion syndrome, need for surgery (7 patients), and death from metastatic NF-PET (1 patient). The mean event-free survival was 13.9 ± 1.1 years after NF-PET diagnosis. At last follow-up, none of the living patients who had undergone surgery or follow-up had evidence of metastases on imaging studies.

Conclusions: Our study shows that conservative management for patients with MEN1 with NF-PET of 2 cm or smaller is associated with a low risk of disease-specific mortality. The decision to recommend surgery to prevent tumor spread should be balanced with operative mortality and morbidity, and patients should be informed about the risk-benefit ratio of conservative versus aggressive management when the NF-PET represents an intermediate risk.

FIGURE 1

Flow chart of study cohort with number of patients and mean follow-up times of the entire cohort and of the subgroups (years ± standard deviation). F/u indicates follow-up.

FIGURE 2

Follow-up of growth of NF-PET in mm, as a function of time in years represented graphically. Time was defined until date of last follow-up, or time until surgery for patients who underwent surgery. Patients who underwent surgery are represented by red lines, patients who were followed clinically by blue lines, the patient who died from MEN1 disease by a black line, the patient who died of a non–MEN1-related cause by a dashed black line, and the patient lost to follow-up by a green line.

FIGURE 3

Kaplan-Meier representation of event-free survival curves after NF-PET diagnosis. A, Overall event-free survival of entire cohort, including surgery, increase in size or secretion, and death as events. B, Surgery-free survival of the entire cohort, in which surgery is defined as the event. The number of patients at risk at each time point is shown below the graphs.