The assessment of Ki-67 for prognosis of gastroenteropancreatic neuroendocrine neoplasm patients: a systematic review and meta-analysis

BACKGROUND: Neuroendocrine neoplasm (NEN) is a group of rare tumors. Among which, gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common group. The World Health Organization (WHO) classified these tumors into three different grades (G1, G2, and G3) based on Ki-67 and mitotic rate, and updated the classification in 2019. Several previous studies proved that Ki-67 was related to tumor prognosis, but others still reported that Ki-67 had no predictive value for tumor prognosis. There are different conclusions between studies regarding the correlation between Ki-67 and tumor prognosis, and there is a lack of studies about this correlation of GEP-NENs. Further analysis is still needed to evaluate the prognostic value of Ki-67 in GEP-NENs, to provide reference for clinical decisions. METHODS: A total of 303 studies were retrieved that included Ki-67, GEP-NENs, prognosis, survival, and other subject terms and keywords. We excluded studies that did not show complete Ki-67 index, number of patients and 5-year survival data available for meta-analysis, non-cohort studies, articles published before 2000 or not published in English. Fifteen studies were finally included to assess the value of Ki-67 in the prognosis of patients with GEP-NENs using a random-effects model. RESULTS: The cumulative 5-year survival rate for GEP-NEN G1 (Ki-67 ≤2%), G2 (Ki-67 2–20%) and G3 (Ki-67 >20%) was 86%, 65%, 25% respectively. The 5-year survival rate of GEP-NEN G1 (Ki-67 <3%, first revised in WHO classification 2017, redefined WHO classification 2019) and G1 (Ki-67 ≤2%, WHO classification 2010) was 97% and 84% respectively. CONCLUSIONS: The overall prognosis of GEP-NENs patients showed a decreasing trend with the increase of Ki-67, which confirmed the significance of Ki-67 index as a prognostic marker for the prognosis of GEP-NENs. Increasing the cut-off value of Ki-67 index for G1 grade from ≤2% to <3% according to WHO classification 2019 did not significantly decrease the 5-year survival rate.