Identifying Risk Factors and Patterns for Early Recurrence of Pancreatic Neuroendocrine Tumors: A Multi-Institutional Study

SIMPLE SUMMARY: Approximately 30% of patients with a pancreatic neuroendocrine tumor (pNET) will develop metastases. Curative-intent treatment largely involves resection. Identifying patients with early recurrence (ER) following resection might help tailor adjuvant therapies and the surveillance intensity. The aim of this retrospective study was to determine an evidence-based cut-off value for ER, and to explore risk factors associated with ER. ER was identified 18 months after surgery. Tumor size (OR 1.20, 95% CI 1.05–1.37, p = 0.007) and positive lymph nodes (OR 4.69, 95%CI 1.41–15.58, p = 0.01) were independently associated with ER. Patients with ER had lower post-recurrence free survival and overall survival than patients with late recurrence. These data support intensive follow-up shortly after surgery, and adjuvant therapy may help improve survival in pNET patients with ER after surgery. ABSTRACT: Background: Identifying patients at risk for early recurrence (ER) following resection for pancreatic neuroendocrine tumors (pNETs) might help to tailor adjuvant therapies and surveillance intensity in the post-operative setting. Methods: Patients undergoing surgical resection for pNETs between 1998–2018 were identified using a multi-institutional database. Using a minimum p-value approach, optimal cut-off value of recurrence-free survival (RFS) was determined based on the difference in post-recurrence survival (PRS). Risk factors for early recurrence were identified. Results: Among 807 patients who underwent curative-intent resection for pNETs, the optimal length of RFS to define ER was identified at 18 months (lowest p-value of 0.019). Median RFS was 11.0 months (95% 8.5–12.60) among ER patients (n = 49) versus 41.0 months (95% CI: 35.0–45.9) among non-ER patients (n = 77). Median PRS was worse among ER patients compared with non-ER patients (42.6 months vs. 81.5 months, p = 0.04). On multivariable analysis, tumor size (OR: 1.20, 95% CI: 1.05–1.37, p = 0.007) and positive lymph nodes (OR: 4.69, 95% CI: 1.41–15.58, p = 0.01) were independently associated with ER. Conclusion: An evidence-based cut-off value for ER after surgery for pNET was defined at 18 months. These data emphasized the importance of close follow-up in the first two years after surgery.