Impact of tumour size on metastasis and survival in patients with pancreatic neuroendocrine tumours (PNETs): A population based study

Background: The relationship between tumour size and metastasis rate is poorly recognized in patients with pancreatic neuroendocrine tumours (PNETs). The impact of tumour size on prognosis was controversial in previous investigations. Methods: PNETs cases diagnosed from 1988 to 2013 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathologic features were retrospectively analyzed. Survival was calculated by the Kaplan-Meier method. Multivariable Cox regression models with hazard ratios (HRs) were constructed to analyze survival outcomes and risk factors. Cubic spline analysis was used to assess relationship between tumor size and probability of metastasis. Results: A total of 5424 patients were identified, 1226 (22.6%) with tumour size of 20mm or less. The probability of metastasis increased in a non-linear fashion with increasing tumour size. Univariate analysis showed that tumour size was significantly correlated with survival (P<0.001), no matter surgery was performed or not. However, subgroup analysis suggested this association to be linear for patients with localized and regional tumours (P<0.001), but stochastic in patients with distant stages (P=0.703). On multivariate analysis, tumour size was an indicator for metastasis (HR=1.010, 95%CI: 1.008-1.013, P<0.001) and size≤20mm was an independent prognostic factor for good survival. For tumours≤20mm, surgical treatment was associated with significantly improved survival (P<0.001). Conclusions: Tumour size affects the probability of metastasis. Its prognostic impact on survival is restricted to patients with localized and regional disease. For patients with tumour size ≤20mm, surgical treatment should be considered preferably.