Gender and Age as Preoperative Predictors of Early Disease Progression in Patients Undergoing Surgery for Pancreatic Neuroendocrine Tumors with Liver Metastases.

Background: Pancreatic neuroendocrine tumor liver metastases (PanNET LMs) are traditionally classified into three types based on their distribution. Surgery is generally considered for patients with type I/II LMs, while those with type III LMs are typically regarded as unresectable; however, type III LMs encompass a wide range of clinical scenarios, some of which may allow surgical resection.

Objective: The aim of this study was to identify preoperative predictors of early progression following surgery (≤6 months) in patients with PanNETs and LMs.

Methods: Consecutive patients with PanNETs and LMs who underwent surgery at San Raffaele Hospital (2010-2023) were included.

Results: After a median follow-up of 56 months, 18/54 patients (34%) experienced early disease progression. Female gender was identified as a protective factor (hazard ratio [HR] 0.373, p = 0.049), while age ≥ 70 years emerged as a significant risk factor (HR 2.744, p = 0.042) for early postoperative progression. When overall disease progression was considered as an outcome, female gender was confirmed as protective (HR 0.426, p = 0.010), while type III LMs significantly increased the risk of progression (HR 2.500, p = 0.012). In the subgroup of patients with type III LMs (n = 37), female gender was confirmed as the only predictor of longer progression-free survival (HR 0.332, p = 0.006).

Conclusions: This study highlights the potential role of surgery for patients with resectable or potentially resectable PanNETs and LMs. For patients with type III LMs, the role of surgery remains controversial. Nevertheless, surgery may still be an option in selected cases, particularly in younger patients and females, as part of a multidisciplinary treatment strategy.