Surgical resection of primary tumor site is associated with prolonged survival in metastatic pancreatic neuroendocrine carcinoma
Authors: T. Feng, S. Ling
Journal: Annals of Oncology (2018)

Introduction: Most of pancreatic neuroendocrine carcinoma (PanNEC) present with distant metastases. According to more aggressive biological behaviors, surgery is not recommended for metastatic PanNEC patients considering the limited survival benefits compared to well differentiated grade patients. However, limited evidences could support these recommendations. The aim of this study was to evaluate the impact of surgical resection of the primary tumor in the patients with PanNEC and distant metastases, as well as identify variables associated with prolonged survival in this patient population. Methods: We used the Surveillance, Epidemiology and End Results (SEER) database to identify patients with PanNEC and distant metastases. The specific criteria are as follows: 1.The histologic subtypes and their International Classification of Disease codes (ICD-O-3) included in the cohort were: large cell neuroendocrine carcinoma(8013), small cell carcinoma(8041) and neuroendocrine carcinoma (8246); 2.Patients with distant metastases according to the "SEER historic stage" variable or AJCC stage IV; 3.histologic differentiation grade included were: poorly differentiated and undifferentiated; 4. the age of patients meet more than 18 years and less than 85 years. Group comparisons of categorical variables were performed using Chi square testing. The Kaplan–Meier method was used to perform a set of actuarial analyses on survival data beginning at the diagnosis date. The difference in survival among groups was determined using a log-rank test. The primary outcome measure in this study was overall survival. Survival times were censored according to the "cancer-specific death" variable. Univariate and multivariable analyses were performed using the Cox proportional hazards regression method. Univariate and Multivariable logistic regression analysis was used to determine the simultaneous impact of factors, which were associated with performing surgery or not. Results: We identified 506 patients with metastatic poorly differentiated and undifferentiated PanNEC and survival data. 15.4%(78/506) of patients had surgical removal of their primary tumor, 24.4% (19/78) of whom had surgical removal of their primary tumor and metastasis. Median survival of patients undergoing surgery was 28 (95% CI: 12.309-43.691) versus 6 (4.671-7.329) months for those without surgery (p < 0.0001). COX multivariable analysis showed tumor site in the body/tail (p = 0.019) and surgical resection of the primary tumor site (p < 0.001) and diagnosis during or after 2010 (p = 0.04), were significantly associated with prolonged survival of patients with PanNEC and distant metastases. Patients diagnosed after 2010 (n = 193, 38.1%) were more likely to undergo an operation than those diagnosed earlier (p<0.001) .To gain insight on patient selection, we analyzed the factors associated with removal of the primary tumor from patients with PanNEC and distant metastases, using a logistic regression model stratified by year of diagnosis since that was not a controllable factor. We found that tumor location in the body/tail of the pancreas were significantly associated with removal of primary tumor, independently of the time period in which patients were diagnosed. In the time period after 2010, female was also associated with removal of primary tumor while age<65y in the time period before 2010. Conclusion: This study suggests that surgical removal of primary PanNEC is associated with longer survival in patients with distant metastases and could therefore be considered as an additional treatment option in this patient population.