Outlook for 615 Small Intestinal Neuroendocrine Tumor Patients: Recurrence Risk after Surgery and Disease-Specific Survival in Advanced Disease

Simple Summary This large single-center study of 615 patients with small intestinal neuroendocrine tumors (siNET) showed that the risk of recurrence after intended radical surgery was high with a recurrence-free survival rate of 40% after 10 years follow-up, and that late recurrencies were frequent. For cases with disseminated disease, the median disease specific survival was around 7 years. Tumor proliferation expressed by Ki-67 index was identified as a prognostic factor whereas proliferation expressed by WHO grade did not predict prognosis. In conclusion, radical intended surgery recurrence rates were high thereby justifying long-term follow-up. Proliferation expressed by Ki-67 index as a continuous variable, rather than grouped according to WHO grading, was an independent prognostic factor for both recurrence-free survival and disease-specific survival supporting the need for reevaluation of the existing grading system.Abstract Background: Small intestinal neuroendocrine tumors (siNET) are one of the most common neuroendocrine neoplasms. Radical surgery is the only curative treatment. Method: We utilized a single-center study including consecutive patients diagnosed from 2000 to 2020 and followed them until death or the end of study. Disease-specific survival and recurrence-free survival (RFS) were investigated by Cox regression analyses with the inclusion of prognostic factors. Aims/primary outcomes: We identified three groups: (1) disease specific-survival in the total cohort (group1), (2) RFS and disease-specific survival after intended radical surgery (group2), (3) disease specific-survival in patients with unresectable disease or residual tumor after primary resection (group3). Results: In total, 615 patients, with a mean age (SD) 65 +/- 11 years were included. Median (IQR) Ki-67 index was 4 (2-7)%. Median disease-specific survival in group1 was 130 months. Median RFS in group2 was 138 months with 5- and 10-year RFS rates of 72% and 59% with age, plasma chromogranin A (p-CgA) and Ki-67 index as prognostic factors. The ten year disease-specific survival rate in group2 was 86%. The median disease-specific survival in group3 was 85 months with age, Ki-67 index, p-CgA and primary tumor resection as prognostic factors. When proliferation was expressed by WHO grade, no difference was observed between G1 vs. G2 for any of the primary outcomes. Conclusions: Recurrence rates remained high 5-10 years after surgery (group2) supporting long-term follow-up. Median disease-specific survival in patient with unresectable disease (group3) was 7 years, with a favorable impact of primary tumor resection. Our data does not support the current grading system since no significant prognostic information was detected in G1 vs. G2 tumors.