Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with liver metastases of digestive endocrine carcinomas

Abstract

The prognosis remains ill-defined in patients with liver metastases of well-differentiated (WD) digestive endocrine carcinomas (DEC) with high Ki-67 index. The objectives of this study were to determine whether Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with DEC, and whether chemotherapy commonly used in patients with poorly differentiated (PD) carcinomas might be applied to those with high Ki-67 index but well-differentiated DEC. Sixty-three patients with DEC metastatic to the liver were retrospectively studied and divided into three prognostic groups. Group 1 comprised patients with well-differentiated carcinomas and Ki-67 index<15% (n=28), group 2 comprised those with well-differentiated carcinomas and Ki-67 index≥15% (n=17), and group 3 comprised those with poorly differentiated carcinomas (n=18). Therapeutic strategy was decided in accordance to guidelines, and tumoral response rate was assessed by computed tomography scan (RECIST). Prognostic factors were determined by uni/multivariate analysis. The 5-year survival rates were 89, 36, and 6% in groups 1, 2, and 3 respectively (P<0.001). Multivariate analysis showed that Ki-67 index≥15%, poor tumor differentiation, and large liver tumor burden were independent predictors of poorer survival. Disease control rates after etoposide-cisplatin were 50 and 53% in groups 2 and 3 respectively (NS). In conclusion, Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with liver metastases of DEC. Patients with well-differentiated carcinomas with high Ki-67 index (≥15%) have intermediate prognosis and a similar response rate to the etoposide-cisplatin combination as those with poorly differentiated carcinomas.