Recurrence in Patients With Lymph Node-Negative Pancreatic Neuroendocrine Tumors.

Area of Science:

• Oncology
• Endocrinology
• Surgical Pathology

Background:

• Lymph node (LN) metastasis is a key predictor of recurrence in pancreatic neuroendocrine tumors (PanNETs) after surgery.
• However, many patients without LN metastasis still experience tumor recurrence, highlighting a need for better risk stratification tools.

Purpose of the Study:

• To develop and validate a risk score for predicting tumor recurrence and survival in patients with LN-negative PanNETs.
• To identify key predictors of recurrence in this patient cohort.

Main Methods:

• Retrospective analysis of 770 patients with localized PanNETs and negative nodal status from 5 institutions (2000-2023).
• Development of a 13-point composite risk score based on multivariable logistic regression of independent predictors.
• Validation of the score using C statistics and assessment of disease-free survival (DFS) via Kaplan-Meier and log-rank methods.
• Genomic profiling in an external cohort to identify recurrence-associated mutational signatures.

Main Results:

• The risk score identified independent predictors: male sex, tumor size ≥3 cm, WHO grade 2+, and lymphovascular invasion.
• The score demonstrated strong predictive performance (AUC 0.83 internally, 0.95 externally).
• Recurrence rates were 2.4% (low-risk), 9.0% (moderate-risk), and 27.7% (high-risk); 10-year DFS rates were 96.1%, 83.6%, and 51.3%, respectively (P<.001).
• Genomic analysis revealed higher tumor mutational burden and specific gene mutations (e.g., DAXX, MTOR) in recurrent tumors.

Conclusions:

• A validated risk score effectively stratifies recurrence and survival risk in LN-negative PanNET patients.
• The score has biological relevance and can inform risk-adapted postoperative surveillance and therapeutic strategies.
• This tool aids in managing patients who lack LN metastasis but remain at risk for PanNET recurrence.