Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors—Need for a Conductor

Abstract

Pancreatic neuroendocrine tumors (pNETs) are a vast growing disease. Over 50% of these tumors are recognized at advanced stages with lymph node, liver, or distant metastasis. An ongoing controversy is the role of surgery in the metastatic setting as dedicated systemic treatments have emerged recently and shown benefits in randomized trials. Today, liver surgery is an option for advanced pNETs if the tumor has a favorable prognosis, reflected by a low to moderate proliferation index (G1 and G2). Surgery in this well-selected population may prolong progression-free and overall survival. Optimal selection of a treatment plan for an individual patient should be considered in a multidisciplinary tumor board. However, while current guidelines offer a variety of modalities, there is so far only a limited focus on the right timing. Available data is based on small case series or retrospective analyses. The focus of this review is to highlight the right time-point for surgery in the setting of the multimodal treatment of an advanced pancreatic neuroendocrine tumor.

What have we learnt from the past – would treatment decisions for GEP-NET patients differ between 2012 to 2016 by the new recommendations in 2022?

“…On the contrary, in highly selected cases the choice for the right timing of liver surgery in oligometastatic GEP-NETs improves survival and the liver-directed strategy should be discussed among an expert team in NET and liver surgery, mostly placed at ENETS CoE [26,59,60]. In advanced disease, we investigated a benefit of PFS after treatment with SSA and systemic treatment, if patients underwent prior surgery or endoscopic resection.…”

“…Curative treatment of GEP-NETs is only possible by surgical or endoscopic resection. This also refers to patients with limited (regional) disease or oligometastatic situation, whereas palliative surgery or ablation for symptom relief may also be considered in selected cases [24][25][26]. Over the last decades, treatment of metastatic NET has dramatically evolved, providing novel strategies.…”

Evolutionary Trajectories of Primary and Metastatic Pancreatic Neuroendocrine Tumors Based on Genomic Variations

“…More than 50% of PanNETs patients are diagnosed at advanced stages with lymph node, liver, or distant metastasis. The 5-year survival rate for patients with untreated liver metastases ranges from 20% to 40% [ 7 ]. Understanding the genetic basis of disease progression would thus allow physicians to cater personalized treatments to achieve a more positive outcome.…”