Curative Surgery and Ki-67 Value Rather Than Tumor Differentiation Predict the Survival of Patients With High-grade Neuroendocrine Neoplasms

Abstract

Objective: To elucidate the role of surgery in patients with high-grade neuroendocrine neoplasms (hg-NENs) and Ki-67 more than 20%. Background: Although surgery is the first treatment choice in patients with low-grade NENs, whether it increases the survival of patients with hg-NENs is debatable. Methods: Between 2005 and 2018, 63 patients pathologically diagnosed with hg-NENs treated at our institution were retrospectively analyzed. The risk factors for overall survival (OS) and recurrence-free survival were analyzed, and OS was compared between each treatment group. Results: The median observation time was 21.2 months, and the median Ki-67 value was 52%. Patients with hg-NENs were classified into low Ki-67 (Ki-67 < 52%) and high Ki-67 (Ki-67 ≥52%) groups. Multivariate analysis for OS identified surgery (P = 0.013) and low Ki-67 value (P = 0.007) as independent risk factors, whereas morphological differentiation defined by the WHO 2017 criteria showed no association with OS. Patients with low Ki-67 value subjected to R0/1, R2, and chemotherapy had a median survival time of 83.8, 16.6, and 28.1 months, respectively. The median survival time for R0/1 group was significantly longer than that for chemotherapy group (P = 0.001). However, no difference in survival was reported between patients from R0/1 and chemotherapy groups with high Ki-67. Ki-67 value could determine recurrence-free survival (P = 0.006) in patients who underwent R0/1 surgery for pancreatic hg-NENs. Conclusions: R0/1 surgery predicted prognoses in the low Ki-67 group. The indication of surgery for patients with hg-NENs did not depend on tumor differentiation.

Surgical outcomes of gastro‐entero‐pancreatic neuroendocrine tumors G3 versus neuroendocrine carcinoma

“…Another study using the SEER database reported on 350 patients with pancreatic NEC, 82% of whom did not undergo resection; among the subset of patients who did undergo surgical removal of the primary tumor, OS was longer compared with nonsurgical patients 30 . Distant metastasis was associated with much worse prognosis as patients with M1 stage had a median OS of only 15.9 months in the current study, which was similar to data in previous reports 17,31 . Collectively, surgical resection may be considered among patients with GEP‐NET G3 and NEC if the primary tumor is localized, yet the benefit of surgical resection was marginal among individuals with metastatic disease.…”

“…30 Distant metastasis was associated with much worse prognosis as patients with M1 stage had a median OS of only 15.9 months in the current study, which was similar to data in previous reports. 17,31 Collectively, surgical resection may be considered among patients with GEP-NET G3 and NEC if the primary tumor is localized, yet the benefit of surgical resection was marginal among individuals with metastatic disease.…”

Single-cell sequencing identifies differentiation-related markers for molecular classification and recurrence prediction of PitNET

“…In addition, the new differentiation classification could also stratify the predictive ability of the Ki-67 index, a proliferative marker widely used as a predictor of tumor recurrence. 54 , 55 , 56 We found that, in well-differentiated PIT1 PitNETs, Ki-67 holds excellent predictive value for tumor recurrence, while in poorly differentiated PIT1, TPIT, or SF1 PitNETs, the predictive value for tumor recurrence was limited. These may explain the conflicting results of Ki-67 prediction value in gonadotroph tumors or nonfunctioning pituitary adenomas.…”

Expert Consensus Practice Recommendations of the North American Neuroendocrine Tumor Society for the management of high grade gastroenteropancreatic and gynecologic neuroendocrine neoplasms

“…Factors associated with improved OS were Ki-67 <55% and receiving adjuvant chemotherapy. A retrospective analysis from Japan included 63 patients with G3 NEN and found that surgery and low Ki-67 value (<52%) were independent factors associated with improved survival ( Asano et al 2020 ). There was no difference in survival between those undergoing surgery vs chemotherapy in patients with a higher Ki-67 (≥52%).…”