Role of Resection of the Primary Pancreatic Neuroendocrine Tumour Only in Patients with Unresectable Metastatic Liver Disease: A Systematic Review

Abstract

Background: Surgery remains the only curative option for pancreatic neuroendocrine tumours (PNETs), but its indication is limited by metastatic disease in most patients. Indication for removing the primary lesion only in the setting of unresectable liver disease is controversial. The present systematic review aims at determining the potential bene- fits (survival, progression-free survival) or harms (morbidity, mortality) of surgical resection of the primary lesion only in patients with PNETs and unresectable metastases. Meth ods: Medline was queried for studies reporting the outcome of PNET patients with unresectable liver metastases whenever there was an explicit comparison between resection of the primary lesion only (‘active treatment’) and no resection (‘non-active treatment’). The primary outcome was survival; possible secondary outcomes were progression-free survival, treatment-related mortality and morbidity, and relief of symptoms. Results: Only 3 cohort studies found were eligible and analysed; no meta-analysis could be performed. The number of patients undergoing ‘active treatment’ varied from 16 to 20, with a percentage ranging from 17 to 39% of cohorts. Survival was longer in patients who received ‘active treatment’ in 2 studies, and the 5-year survival rate also seemed higher, without significant complications. Discussion: Available data suggest a possible benefit of resection of the primary lesion only in this setting. However, a bias towards a more aggressive surgical approach in patients with a better performance status or less advanced disease seems likely, and no conclusion can be drawn except for the need of randomised trials. We calculated that such a trial would require at least 118 patients per arm.

Neuroendocrine tumor disease: an evolving landscape

“…Patients with Ki-67 !2% have a 5-year survival rate of 80% compared with 40% for those with Ki-67 O2% (Ekeblad et al 2008). Results of surgery in PNENs with vascular involvement, of mainly the portal vein, are encouraging and surgery should also be considered for the treatment of LM (Bartsch et al 2000, Kouvaraki et al 2005, Akerstrom & Hellman 2009, Capurso et al 2011. In general, surgical approach is recommended in well-differentiated NENs (WHO groups I and II), whereas patients with poorly differentiated NEC (WHO group III) should primarily be treated with chemotherapy.…”

Controversies in the treatment of digestive neuroendocrine tumors

“…[8] In the literature, clinical studies suggest that there is a possible benefit in terms of survival when performing surgical removal of primitive pNETs if metastases are present. [9] However, in the retrospective studies that evaluated the role of surgery in pNETs with unresectable liver metastases, there is a selection bias for patients related to the localization of primary tumors and the type of surgical approach, the patient status in terms of comorbidity, age and performance status. [9] In the Partelli et al [10] paper, the 5-year overall survival (OS) after surgical resection was 76% with an increase to 88% after curative resection.…”

“…[9] However, in the retrospective studies that evaluated the role of surgery in pNETs with unresectable liver metastases, there is a selection bias for patients related to the localization of primary tumors and the type of surgical approach, the patient status in terms of comorbidity, age and performance status. [9] In the Partelli et al [10] paper, the 5-year overall survival (OS) after surgical resection was 76% with an increase to 88% after curative resection. Although palliative surgery was associated with an improved outcome, surgical management should be reserved in highly selected patients due to the high risk of peri/postoperative complications.…”

Non-functioning neuroendocrine tumors of the common hepatic duct: a case report and literature review

“…30 Circumferential invasion of either the portal vein with portal cavernoma or the superior mesenteric artery is considered a contraindication for surgery. 31 As for the metastases resection, surgery is recommended only for G1 and G2 (well differentiated) tumors where more than 90% of the tumor burden must be removed. The aim of surgery is to prevent life-threatening and obstructive complications.…”

“…The aim of surgery is to prevent life-threatening and obstructive complications. 31 Regarding liver metastases surgery, resection combined to ablative therapy and systemic treatment based on the location and the tumor resecability is indicated. 32 However, liver transplantation has been offered as an alternative treatment for liver metastases in selected cases.…”