Introduction

The management of small, non-functional pancreatic neuroendocrine incidentalomas (NF-NEI) is challenging. Without signs of malignancy, there is no established algorithm to decide between surgery and surveillance.

Aims & Methods

The main aim of the study was to assess the incidence of malignancy in sporadic NF-NEI ≤2 cm. The secondary aim was to identify the progression rate at 3 years of non-operated lesions defined as increasing tumor size > 20%, and/or > 2mm/year, and/or the appearance of lymph node, and/or distant metastases. This was a multicenter prospective study, conducted in 12 centers, included prospectively and consecutively between December 2016 and June 2019 all patients with NF-NEI ≤2 cm. The diagnosis must have been proven by a positive EUS-guided FNA/FNB or positive somatostatin receptors imaging (SRI)). The exclusion criteria were: grade G3 tumor at the time of inclusion and MEN 1 syndrome. Two groups of patients were defined based on their management, decided by the referring center: non-surgical (surveillance) and surgical (carried out within 6 months after inclusion). The diagnosis of malignancy was retained if at least one of the following criteria was met: G3 tumor, presence of lymph node and/or distant metastases, doubling in size of the primary tumor during the 36 months of follow-up (FU). Surveillance was performed by imaging and EUS.

Results

111 patients were included (43 men, 68 women, median age 63 years (IQR, 52-70)). In EUS, the median size of the pancreatic lesion was 13 (IQR, 10-16) mm. The EUS-guided fine needle biopsy confirmed neuroendocrine tumor in 105 cases (G1 = 83 (79%), G2 = 4 (4%), non-evaluable grade = 18 (17%). In 6 cases the biopsy was noncontributory. The radionuclide imaging (RNI) performed in 42 patients showed hyperfixation of the lesion in 62% of cases without distant lesion. Due to symptoms (3), suspicion of malignancy (3), by decision of the tumorboard (11) and patient request ( 2), 19 (17%) patients were operated within a median time of 2.76 months (IQR 1.6-4.6) after inclusion. The diagnosis and final classification were: 14 G1 (73.7%) and 5 G2 (26.3%); 17 (89.3%) pT1N0 and 2 (11.8%) pT1N1. 92 (83%) patients had active surveillance. The median follow-up was respectively 38.4 (95% CI, 26, 3-43.6) and 37.8 (36.1-39.7) months in the surgery and surveillance groups. Due to the significant increase in size of the primary tumor, 4 patients in the surveillance group were operated on in a median time of 17.1 months (IQR 11.7-20.8) after inclusion (3 G1 pT1N0, 1 G2 pT1N1). The rate of surgical complications was 26.1% (6/23 patients), including 4 fistulas and 2 bleeds. In total, 4 (3.6%) patients presented malignancy criteria: 3pN+ on the surgical resection specimen (surgery (2), surveillance (1) groups); 1 patient in the surveillance group with a G1 lesion of 15 mm at the time of inclusion, which doubled in size and developed metastatic disease 12 months after diagnosis. During follow-up, 2 (2%) deaths unrelated to pancreatic NET occurred. No recurrence was observed in operated patients. In total, the incidence of malignancy and the rate of progression at 3 years were 3.6% and 4.5% respectively.

Conclusion

Our study shows a low rate of baseline malignancy among small (≤2cm) NF-NEI and in terms of progression over a relatively short 3-year timeframe. Our data highlight the need for careful initial evaluation and identification of more accurate predictors of disease progression to better determine disease course and management. Surveillance strategies require multidisciplinary discussion and thorough patient counseling.

Disclosure

This study endorsed by SFED, obtained the FARE grant from the SFNGE, support from the biopharmaceutical group Ipsen and assistance from the FFCD for the statistical analysis.