729P - Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumors (NF-PanNETs): A survival analysis from a prospective observational study

Background

Nodal metastases (N+) are one of the most powerful predictors of disease recurrence after surgery for non-functioning pancreatic neuroendocrine tumors (NF-PanNETs). However, the prognostic role of nodal metastases < 5 mm, defined as micrometastases, has been poorly investigated so far. The aim of this study was to compare clinico-pathological features and survival outcomes between patients with NF-PanNETs without nodal involvement (N0), with nodal micrometastases (microN+) and with nodal macrometastases (macroN+).

Methods

Consecutive patients who underwent a formal pancreatic resection for NF-PanNETs at San Raffaele Hospital (Milan, Italy) between 2018 and 2021 and were enrolled in the DETECTYON trial were considered (NCT03918759). Nodal metastases were further classified as microN+ when their maximum diameter was < 5 mm, or as macroN+ when their maximum diameter was ≥ 5 mm.

Results

Overall, 100 patients were included. Of these, 58 had N0 PanNETs, 15 had microN+ and 27 had macroN+. Patients with macroN+ had significantly larger tumors [median 35 mm (IQR 28-47)] as compared to patients with microN+ [25 mm (IQR 24-35), p=0.040] and N0 neoplasms (26 mm (IQR 18-34), p=0.003]. The rate of G2-G3 neoplasms was comparable between patients with N0 and microN+ PanNETs (45% versus 27%, p=0.203), whereas it was significantly higher among subjects with macroN+ tumors (n=21/27 - 78%). Median Ki67 was 2% in patients with N0 and microN+ neoplasms (p=0.429), whereas it increased to 6% in patients with macroN+ (p=0.006). After a median follow-up of 37 months, 16 patients (16%) experienced disease relapse. Patients with N0 PanNETs had a 4-year DFS rate of 97% as compared with 88% and 43% in patients with microN+ (p=0.152) and macroN+ (p<0.001), respectively. At multivariable analysis, distant metastases (HR 5.826, p=0.026) and macroN+ (HR 6.281, p=0.034) were identified as independent determinants of disease relapse.

Conclusions

NF-PanNETs with microN+ seem to be associated with a risk of recurrence similar to N0 neoplasms. MicroN+ may be regarded as a clinicopathological entity separate from macroN+, with a possible impact on postoperative surveillance protocols.

Clinical trial identification

These are the long-term outcomes of a prospective observational study: NCT03918759.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.