Reassessment of proliferative activity at disease progression in neuroendocrine neoplasms

Background

The proliferative index Ki-67 is a key prognostic factor influencing prognosis and therapeutic approach in NENs. However, the role of histological reassessment at time of progression of disease (PD) is still debated. The aim was to investigate Ki-67 modifications at time of PD in NENs.

Methods

Analysis of sporadic NENs in which histology was repeated at time of PD. Values are expressed as median (range), and compared by Wilcoxon test.

Results

48 pts, median age 56 (23-74 yr), were included. Among these, at time of PD, 33.4% (16 pts) had recurrent disease after previous radical surgery, and 66.6% (32 pts) showed increase in lesions number/size. Primary tumour were prevalent pancreas (52%, 25 pts) and distal jejunum/ileum (33.4%, 16 pts). At time of initial evaluation, 47.9% of pts (n = 23) had G1 tumour, whereas 52.1% (n = 25) had G2 tumour. Median Ki-67 was 3% (1%-20%). The median interval between initial assessment and repeated histology was 54 months (2-148). During this period, patients received the following treatments: somatostatin analogs (52%, 25 pts), PRRT (25%, 12 pts), systemic chemotherapy (10.4%, 5 pts), everolimus (14.6%, 7 pts). At time of PD, 64.6% of pts (n = 31) showed increase in Ki-67 (21 pancreas, 8 distal jejunum/ileum, 2 other primary NENs). A G grading step-up was observed in 15 pts (11 pNENs, 4 non-pNENs): 11 pts changed from G1 to G2, 4 pts from G2 to G3. Overall, median Ki-67 increased to 7,5% (range 1%-70%; p = 0.0003 vs Ki-67 at time of initial assessment). Specifically, Ki-67 significantly changed in pNENs from a median value of 4% to 12% (p = 0.0002), whereas no significant change occurred in non-pNENs rising from a median value of 2% to 5% (p = 0.32). As far as the kind of PD is concerned, no difference in terms of Ki-67 change was observed between patients who underwent increase in size/number of lesions, and those who underwent disease recurrence after radical surgery.

Conclusions

Ki-67 increase occurred in 64.6% of NENs at time of PD. A statistically significant modification was observed in pNENs. Reassessment of proliferative activity at time of progression should be considered, especially in pNENs. This information might help physicians to plan proper patients' management.

Clinical trial identification

Legal entity responsible for the study

"Sapienza" University of Rome

Funding

"Sapienza" University of Rome

Disclosure

All authors have declared no conflicts of interest.