Related Experiment Video
Updated: Jan 8, 2026
An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
Recurrence in Patients With Lymph Node-Negative Pancreatic Neuroendocrine Tumors
Marco Ventin1, Shahrzad Arya1, Liti Zhang1
1Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
Importance:
Lymph node (LN) metastasis is a strong predictor of tumor recurrence following pancreatectomy for localized pancreatic neuroendocrine tumors (PanNETs). However, most patients lack LN metastasis and many tumors recur. Tools to guide risk-adapted surveillance in this group are lacking.
Objective:
To develop and validate a tumor recurrence and survival risk score for patients with LN-negative PanNETs.
Design, Setting, And Participants:
This retrospective, case-control study of patients with localized PanNETs took place at 5 high-volume US institutions from 2000 to 2023. Inclusion required 8 or more evaluated LNs and negative nodal status. Median follow-up was 50.6 months. These data were analyzed from March 2025 to May 2025.
Exposure:
Surgical resection of localized PanNETs per clinical guidelines.
Main Outcomes And Measures:
The primary outcome was tumor recurrence. Independent predictors were identified using multivariable logistic regression and used to construct a 13-point composite risk score. Performance was assessed using C statistics. Kaplan-Meier and log-rank methods evaluated disease-free survival (DFS). Genomic profiling was conducted in an external validation cohort to identify and validate recurrence-associated mutational risk scores.
Results:
Of 2024 patients, 770 met inclusion criteria. Median age was 58.7 (IQR, 18.4) years; 405 were male (52.6%) and 365 were female (47.4%). Most tumors were sporadic (94.1%), nonfunctional (90.4%), and located in the body/neck (50.9%). Recurrence occurred in 82 patients (10.6%) at a median of 32.4 (IQR, 16.3-82.0) months after surgery. Independent predictors included male sex (odds ratio [OR], 2.2; 95% CI, 1.3-3.9), tumor size 3 cm or larger (OR, 2.64; 95% CI, 1.5-4.6), World Health Organization grade 2 or higher (OR, 3.70; 95% CI, 1.4-10.0), and lymphovascular invasion (OR, 3.84; 95% CI, 2.1-6.9). The risk score showed strong performance (area under the receiver operating characteristic, 0.83 internally; 0.95 externally). Recurrence rates by risk group were 2.4%, 9.0%, and 27.7% (P < .001), and 10-year DFS rates of 96.1%, 83.6%, and 51.3%, for low-risk, moderate-risk, and high-risk groups, respectively (P < .001). Genomic analyses revealed higher tumor mutational burden, somatic mutation count, and somatic mutations in CDC42BPB, DAXX, ERI2, GALNT9, MTOR, NUMA1, and TRPC7 genes among recurrent tumors.
Conclusions And Relevance:
Despite LN-negative status, a subset of patients with PanNETs remained at high risk for recurrence. This validated risk score stratifies recurrence and survival risk showing biological relevance. These findings provide a framework for refining postoperative surveillance and risk-adapted therapeutic strategies.
