Surgical treatment for neuroendocrine liver metastasis: moving ahead in controversy.

HepatoBiliary Surg Nutr 2021 | https://dx.doi.org/10.21037/hbsn-21-360 Despite the indolent nature of neuroendocrine tumors (NETs), 45–90% of patients experience neuroendocrine liver metastasis (NELM) during the disease course (1). These patients will develop systemic symptoms secondary to the liver lesions, decreasing both quality of life and prognosis (2). Frilling et al. reported a 5-year overall survival (OS) of 13–54% in NELM patients, which was significantly lower than the 75–99% OS for patients without hepatic metastases (3). Surgical treatment plays an important role and has been accepted as the only potential curative option for appropriately selected patients with NELM. However, controversy continues to exist regarding indications for surgery and effectiveness. Over the past few years, a variety of treatment options have improved the outcomes of NELM patients, including surgery, non-operative hepatodirected treatment, and systemic therapy. As Cloyd et al. stated in a current review of NELM management (4), a multidisciplinary and comprehensive evaluation is important when selecting patients for appropriate treatment approaches. Herein, we summarize some key issues related to surgical treatment for NELM that need to be resolved in future research. Several studies have reported therapeutic benefits of surgery for NELM, and surgical resection is widely employed when feasible. An international multicenter review of over 300 NELM patients undergoing hepatectomy reported a 5-year survival of 74%, which was superior to the OS of 30% in patients treated with intra-arterial therapies (1). In contrast, a systematic review found no evidence for long-term survival benefit of liver resection compared with any other liver-directed therapies (5). Since prospective randomized controlled trials are unlikely to be conducted, the dispute will continue. The fundamental reason behind the controversy is the range of surgical indications. The impact of hepatectomy on long-term prognosis is still difficult to assess due to potential selection bias for different treatments. For example, patients with heavier disease burden, worse performance status, and severe comorbidities tend to receive conservative treatment and are more likely to have poor outcomes. The European Neuroendocrine Tumor Society (ENETS) guidelines recommend hepatic resection for NELM patients as long as R0 resection is feasible, tumors are classified as grade 1 or 2, there are no extrahepatic metastases, and perioperative morbidity is <30% and mortality <5% (5). However, due to the heterogeneity of NETs, “off-label” indications for hepatectomy are not uncommon. Debulking is gradually being an accepted treatment strategy for patients who cannot undergo complete resection of all lesions. Previous studies have reported comparable OS in patients receiving cytoreductive surgery in which 70–90% of lesions were resected (6). Specifically, there is ongoing debate over resection of the primary tumor in the setting of unresectable metastasis. While improvement of long-term survival was observed in a systematic review of primary tumor resection for unresectable NELM, other research has reported limited benefit for symptomatic patients (7). The proposed rationale behind the approach is to relieve symptoms caused by the primary tumor, prevent Editorial