Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort

Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)

“…In the WHO 2010 classification of the digestive system and the 2017 classification of endocrine tumors (including pancreatic NEN), NEN G3 are defined as neoplasms with a high proliferation rate (Ki-67 index > 20% or > 20 mitotic figures/2 mm 2 ) but frequently the Ki-67 index is above 70% for NEC [1,2,5,7,17]. Most studies have shown that a higher Ki-67 proliferation rate is a worse prognostic factor and may be predictive of treatment benefit, although further validation of this is necessary [5,7,11,13,17,[25][26][27]. The specific Ki-67 value should therefore always be provided in pathology reports as an absolute measure of the hot spot, i.e., the area with the highest score and possibly complemented by recording heterogeneity [28].…”

“…Possible prognostic and predictive factors for patients with GEP NEC or NET G3 are highly needed by clinicians to aid in treatment selection for these patients. GEP NEC are usually highly aggressive, with a propensity for early metastases and a dismal prognosis [3][4][5][6][7]. Data on GEP NEC are sparse and treatment has been extrapolated from small-cell lung cancer data.…”

“…There has been an increase in the incidence of GEP NEC over the last 2 decades, although more awareness of this entity among pathologists could partly explain this increase [3,[8][9][10]. NEC can originate anywhere in the GEP tract, but they are mainly located in the esophagus, stomach, pancreas, and large bowel [7,[11][12][13][14]. Given their aggressive nature, most patients have metastatic disease at the time of presentation [5,7,[13][14][15].…”

“…NEC can originate anywhere in the GEP tract, but they are mainly located in the esophagus, stomach, pancreas, and large bowel [7,[11][12][13][14]. Given their aggressive nature, most patients have metastatic disease at the time of presentation [5,7,[13][14][15]. In general, high-quality epidemiological data on NEC are lacking, especially as data on differentiation and proliferation rates to ensure a correct diagnosis are often not available in registries.…”

“…Long-term relapse-free survival is possible among NEC patients with localized disease and seems to depend on the primary site location, but inaccurate TNM classification precludes firm conclusions [14,16]. The mean survival in GEP NEC patients with metastatic disease treated with chemotherapy is 11-12 months [5,7,11,12]. A poor performance status, a high tumor burden, liver metastases, a high proliferation rate, and elevated lactate dehydrogenase levels are usually baseline negative prognostic factors for survival in metastatic disease [7,[11][12][13]17].…”