High rate of Ki-67 increase in entero-pancreatic NET relapses after surgery with curative intent

Abstract

Neuroendocrine neoplasms (NENs) present with advanced disease at diagnosis in upto 28% of cases, precluding the possibility of curative-intent surgery. Histopathologi-cal heterogeneity of this disease can be observed inter-individually as well as intra-individually during disease course. The present study aimed to assess the frequencyof Ki-67 change after radical surgery, in a series of patients with radically resectedentero-pancreatic neuroendocrine tumors (EP-NETs).We present the analysis of a multicenter, retrospective, series of EP-NETs G1–G2recurring after radical resection and with histological re-evaluation at disease recur-rence (DR). The primary endpoint was the description of Ki-67 change at DR com-pared to time of surgery. The secondary endpoint was assessment of recurrence-freesurvival (RFS) rates. In total, 47 patients had a second histological evaluationand could be included in the present study. Median Ki-67 at surgery was 3% (range1–15%) but, at DR, a significant increase in the value was observed (7%, range1–30%;p< .01) and involved 66.0% of cases, with a corresponding increase in tumorgrading in 34.0% (p=.05). Median RFS of the overall population was 40 months, andwas worse when Ki-67 increased at DR vs. stable Ki-67 value (36 vs. 61 months espectively;p=.02). In conclusion, in more than half of the cases with relapse afterradical surgery, a higher proliferative index with a potentially more aggressive poten-tial was observed. Therefore, histological reassessment should be considered on DRbecause tailored therapeutic strategies may be required for these patients.