Comparative analysis of international guidelines on the management of advanced non-functioning well-differentiated pancreatic neuroendocrine tumors

This review presents a comprehensive comparative analysis of international guidelines for managing advanced, non-functioning, well-differentiated pancreatic neuroendocrine tumors (panNETs). PanNETs, which represent a significant proportion of pancreatic neuroendocrine neoplasms, exhibit diverse clinical behaviors and prognoses based on differentiation, grading, and other molecular markers. The varying therapeutic strategies proposed by different guidelines reflect their distinct emphases and regional considerations, such as the ESMO guideline’s focus on advanced disease management and the ENETS guidance paper’s multidisciplinary approach. This review examines the most recent guidelines from ESMO, NCCN, ASCO, ENETS, and NANETS, analyzing the recommendations for first-line therapies and subsequent treatment pathways in different clinical scenarios. Significant variations are observed in the recommendations, particularly concerning the choice and sequence of systemic therapies, the role of tumor grading and the Ki-67 index in therapeutic decisions, and the integration of regional regulatory and clinical practices. The analysis highlights the need for a tailored approach to managing advanced NF panNETs, advocating for flexibility in applying guidelines to account for individual patient circumstances and the evolving evidence base. This work underscores the complexities of managing this patient population and the critical role of a multidisciplinary team in optimizing treatment outcomes.