Abstract
INTRODUCTION: There is no consensus on managing non-functioning pancreatic neuroendocrine tumors smaller than 2 cm (NF-PANNETs < 2 cm). Therefore, their treatment remains controversial. The aim of this study, by literature review and meta-analysis, is to establish the best management of NF-PANNETs < 2 cm based on overall survival (OS) and cancer-specific survival (CSS). MATERIALS AND METHODS: An extensive online search was conducted using the MEDLINE, EMBASE, Google Scholar, Scopus, Web of Science, and Cochrane Central databases. All retrospective and prospective studies were included in this study, comparing the outcomes of surgical management vs. conservative management in patients with NF-PANNETs < 2 cm. The pooled odds ratio and 95% CI for survival were calculated. RESULTS: Six studies were included in the quantitative analysis, with 2708 patients managed operatively and 985 managed conservatively. A pooled analysis of all the data demonstrated increased OS in patients managed operatively compared with those managed conservatively at five years (OR = 1.77, 95% CI: 0.96 to 2.58; p = 0.002). In contrast, the meta-analysis did not demonstrate increased CSS in patients undergoing surgical resection compared with conservative management (OR = 1.01, 95% CI: -5.25 to 7.27; p = 0.56). Furthermore, analysis demonstrated a high heterogeneity for OS (Q = 43.98, p < 0.001, tau(2) = 0.46, I(2) = 88.63%) and for CSS (Q = 22.81, p < 0.0001, tau(2) = 1.72, I(2) = 91.23%). CONCLUSION: This systematic review and meta-analysis indicated that surgical management of NF-PANNETs < 2 cm improves overall survival (OS) but does not significantly enhance cancer-specific survival (CSS). There is variability in outcomes among studies, and while surgery may help some patients, the lack of clear CSS benefits and associated risks call for individualized decision-making. Therefore, a conservative approach with active surveillance may be more suitable for low-risk patients.