The Use of Adjunct Therapies with Surgery for Gastroenteropancreatic Neuroendocrine Tumors: Indications, Timing, and Outcomes

Background/Objectives: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare biologically heterogeneous neoplasms but with increasing incidence in recent years. Surgery remains the backbone of treatment; however, long-term recurrence is common even after curative resection. Despite expanding treatment options, the optimal perioperative integration of adjunct therapies in conjunction with surgery remains incompletely defined, as available evidence is largely retrospective and heterogeneous. This review critically synthesizes available evidence on the role of perioperative therapies in the surgical management of GEP-NENs, identifies key knowledge gaps, and highlights areas where multidisciplinary decision-making is required. Methods: A targeted narrative literature review was performed in PubMed/MEDLINE (2001–2026), supplemented by ClinicalTrials.gov and major society guidelines. Predefined search terms were used to include “gastroenteropancreatic neuroendocrine tumor”, “GEP-NET”, “pancreatic neuroendocrine tumor”, “surgery”, “palliative surgery”, “neoadjuvant”, “adjuvant”, “PRRT”, “somatostatin analogue”, “chemotherapy”, “targeted therapy”, “immune checkpoint inhibitor”, and “liver-directed therapy”. Studies were selected based on relevance, with emphasis on comprehensive reviews, key clinical studies, and major guideline statements. This approach was chosen due to varied literature and scarce high-quality prospective evidence. Results: Neoadjuvant PRRT and CAPTEM-based chemotherapy demonstrate encouraging activity in selected patients with SSTR-positive or borderline resectable pNETs, though evidence is predominantly retrospective and R0 resection rates are inconsistent across modalities. Adjuvant systemic therapy lacks high-quality evidence of benefit in well-differentiated GEP-NETs whereas platinum-based chemotherapy following resection of NEC represents the only setting where adjuvant treatment is commonly recommended, albeit without randomized trial support. Liver-directed therapies, including thermal ablation, TACE, and TARE, play complementary roles in selected patients with hepatic metastases. The overall evidence base is largely retrospective and heterogenous. Management should be individualized through multidisciplinary discussion.