Intestine| Volume 169, ISSUE 6, P1417-1423, June 2021

Does surgery provide a survival advantage in non-disseminated poorly differentiated gastroenteropancreatic neuroendocrine neoplasms?

Published:February 23, 2021DOI:



      Attributable to the high likelihood of developing distant metastatic disease, resection of poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is generally contraindicated. Some patients with no distant metastatic disease will nonetheless undergo surgical resection and their outcomes are not known. We aimed to determine whether surgery confers survival advantage over systemic therapy alone for patients with non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms.


      We performed a retrospective cohort study (2000–2012) of adults in the California Cancer Registry who had poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (World Health Organization Grade 3) and no clinical evidence of distant metastasis (M0). Patients who underwent surgery were compared with those managed non-operatively. The adjusted Cox proportional hazards model was used to assess the risk of death.


      Among 2,245 patients (45% female, 21% pancreatic, 79% gastrointestinal), 1,549 (69%) were treated with surgery, and 696 (31%) received either systemic therapy or palliative measures alone. Median survival was 31 months after surgery versus 9 months after non-operative therapy (log-rank test, P < .001). Rates of 5-year overall survival were 39% after surgery versus 10% in the non-operative group. Adjusting for age, sex, comorbidities, receipt of chemotherapy, and tumor size and location, patients treated with surgery had a 58% lower likelihood of death compared with non-operative therapy (hazard ratio: 0.42, 95% confidence interval: 0.36–0.50, P < .001). Restricting our results to those patients who were found to have no distant metastasis intraoperatively (ie, pathologically M0), 5-year survival after surgery reached 44%.


      While poorly differentiated gastroenteropancreatic neuroendocrine neoplasms carries a poor prognosis, for patients with no evidence of metastatic disease, resection appears to confer significant improvement in long-term survival. Although caution and an individualized approach in treating poorly differentiated gastroenteropancreatic neuroendocrine neoplasms is advised, future guidelines might reflect this survival advantage.
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