The role of chemotherapy in well-differentiated GIT neuroendocrine tumors

Neuroendocrine tumors (NETs) represent 2% of all malignant tumors of the gastrointestinal (GI) neoplasms. Based on morphology, the most common categories are well-differentiated NETs and the poorly differentiated neuroendocrine carcinomas (NECs). NETs are rare tumors with slowly progressive course. However, their incidence has increased in the last decades up to 6.98 new cases/100.000 /year and they have a relatively good prognosis compared to NECs. Somatostatin analogues are the mainstay of treatment for well-differentiated NETs. For grade III NETs, chemotherapy is the first line in treatment due to the aggressive behavior, but it is used in few selected cases in well-differentiated NETs. Although the role of chemotherapy is well established in NECs, data on NETs are limited to small few studies and experts' opinions. So this study aims to evaluate the role of chemotherapy in well-differentiated gastroenteropancreatic NETs to provide additional evidence in the literature for chemotherapy in the treatment of GIT NETs.

We obtained the data of 12,237 patients from Surveillance, Epidemiology and End Results(SEER) software, all of them had GI neuroendocrine tumors with malignant behavour including: NET pancreas,NET stomach, NET colon, NET appendix and NET small intestine. We had two groups: a group for patients who received chemotherapy while the other group had no chemotherapy. We used SPSS 23 IBM for data analysis. Kaplan-Meier curve, Log-rank test for survival analysis.

The overall 5-year age standardized relative survival for well differentiated GI NETs was 93.6% and the 5-year relative survival was 95.6%. The 5-year relative survival for chemotherapy compared to the group who had no chemotherapy was 67.8% and 96.2%; P < 0.001. Out of 12237 patients with well-differentiated GI NETs, 66.9% patients had localized tumor, 17.8% had regional stage and 7.8% had distant metastasis with overall 5-year relative survival for each stage 97.4%, 96.4% and 77.5% respectively; P < 0.001. Males had quite similar survival to females but statistically significant (68% and 67%; P < 0.001). Performing COX-regression model, localized stage was associated with improved survival outcome (HR=0.47, 95%CI: 0.404-0.557, P < 0.0001) while chemotherapy (HR=1.92, 95%CI: 1.513-2.447, P < 0.0001), age (HR=1.92, 95%CI: 1.513-2.447, P < 0.0001), sex (HR=1.221, 95%CI: 1.087-1.372, P < 0.001) and black race (HR=1.678, 95%CI: 1.278-2.203, P < 0.0001) were associated with poor survival outcome.

These results demonstrate no survival benefit from adding chemotherapy to the treatment regimen of well-differentiated GI neuroendocrine tumors. In addition, chemotherapy had increased risk to worsen the survival outcome by two folds and the group who received no chemotherapy had approximately survival benefit of 30% compared to the group who received chemotherapy. So, we recommend to avoid chemotherapy in well-differentiated GI NETs to improve the survival outcome and decrease complications associated with the systemic therapy.

The authors.

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All authors have declared no conflicts of interest.